Revision as of 01:10, 22 January 2020

Section editor
	Sanjai Sharma, MD Sequoia Regional Cancer Center Visalia, CA

Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page. If you still can't find it, please let us know so we can add it!

84 regimens on this page 138 variants on this page

Guidelines

ESMO

Current

2016: Dreyling et al. Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Older

2014: Dreyling et al. Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
2013: Ghielmini et al. ESMO Guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL) PubMed

Early disease, definitive therapy

Ibritumomab tiuxetan monotherapy

back to top

Regimen

Study	Evidence
Samaniego et al. 2014 (MDACC 2005-0512)	Phase II

Radioimmunotherapy

Rituximab (Rituxan) 250 mg/m² IV once per day on days 1 & 8, given first
Ibritumomab tiuxetan & Yttrium-90 (Zevalin) given second, as follows:
- Platelet count greater than 150 x 10⁹/L: 14.8 MBq/kg (maximum dose of 1184 MBq) IV once on day 8
- Platelet count between 100 and 149 x 10⁹/L: 11.1 MBq/kg (maximum dose of 1184 MBq) IV once on day 8

References

MDACC 2005-0512: Samaniego F, Berkova Z, Romaguera JE, Fowler N, Fanale MA, Pro B, Shah JJ, McLaughlin P, Sehgal L, Selvaraj V, Braun FK, Mathur R, Feng L, Neelapu SS, Kwak LW. 90Y-ibritumomab tiuxetan radiotherapy as first-line therapy for early stage low-grade B-cell lymphomas, including bulky disease. Br J Haematol. 2014 Oct;167(2):207-13. Epub 2014 Jul 8. link to original article contains verified protocol PubMed

Radiation therapy

back to top

RT: Radiation Therapy

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Yahalom et al. 1993
Kelsey et al. 1994	Non-randomized portion of RCT
Lowry et al. 2011	Phase III (E-de-esc)	RT x 40 to 45 Gy	Did not meet primary endpoint of ORR
Hoskin et al. 2014 (FORT)	Phase III (C)	RT x 4 Gy	Superior TTP
MacManus et al. 2018 (TROG 99.03)	Non-randomized portion of RCT

This is the current "standard dose" radiotherapy - dose varies per protocol and location radiated.

Radiotherapy

External beam radiotherapy 24 to 36 Gy

Subsequent treatment

Yahalom et al. 1993: CHOP versus no further treatment
Kelsey et al. 1994: Chlorambucil versus no further treatment
TROG 99.03: CVP or R-CVP versus no further treatment

References

Yahalom J, Varsos G, Fuks Z, Myers J, Clarkson BD, Straus DJ. Adjuvant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy after radiation therapy in stage I low-grade and intermediate-grade non-Hodgkin lymphoma: results of a prospective randomized study. Cancer. 1993 Apr 1;71(7):2342-50. link to original article PubMed
Kelsey SM, Newland AC, Hudson GV, Jelliffe AM. A British National Lymphoma Investigation randomised trial of single agent chlorambucil plus radiotherapy versus radiotherapy alone in low grade, localised non-Hodgkins lymphoma. Med Oncol. 1994;11(1):19-25. link to original article PubMed
Lowry L, Smith P, Qian W, Falk S, Benstead K, Illidge T, Linch D, Robinson M, Jack A, Hoskin P. Reduced dose radiotherapy for local control in non-Hodgkin lymphoma: a randomised phase III trial. Radiother Oncol. 2011 Jul;100(1):86-92. Epub 2011 Jun 12. link to original article PubMed
FORT: Hoskin PJ, Kirkwood AA, Popova B, Smith P, Robinson M, Gallop-Evans E, Coltart S, Illidge T, Madhavan K, Brammer C, Diez P, Jack A, Syndikus I. 4 Gy versus 24 Gy radiotherapy for patients with indolent lymphoma (FORT): a randomised phase 3 non-inferiority trial. Lancet Oncol. 2014 Apr;15(4):457-63. Epub 2014 Feb 24. link to original article PubMed
TROG 99.03: MacManus M, Fisher R, Roos D, O'Brien P, Macann A, Davis S, Tsang R, Christie D, McClure B, Joseph D, Jayamohan J, Seymour JF. Randomized trial of systemic therapy after involved-field radiotherapy in patients with early-stage follicular lymphoma: TROG 99.03. J Clin Oncol. 2018 Oct 10;36(29):2918-2925. Epub 2018 Jul 5. link to original article PubMed

Early disease, adjuvant therapy

Observation

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Kelsey et al. 1994	Randomized (C)	CHOP x 6	Seems to have inferior RFS
Kelsey et al. 1994	Randomized (C)	Chlorambucil	Did not meet primary endpoint of OS
MacManus et al. 2018 (TROG 99.03)	Randomized (C)	1. CVP 2. R-CVP	Seems to have inferior PFS

No further treatment. Note that in TROG 99.03, patients enrolled after 2006 were randomized between this arm and R-CVP.

Preceding treatment

Radiation therapy

References

Yahalom J, Varsos G, Fuks Z, Myers J, Clarkson BD, Straus DJ. Adjuvant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy after radiation therapy in stage I low-grade and intermediate-grade non-Hodgkin lymphoma: results of a prospective randomized study. Cancer. 1993 Apr 1;71(7):2342-50. link to original article PubMed
Kelsey SM, Newland AC, Hudson GV, Jelliffe AM. A British National Lymphoma Investigation randomised trial of single agent chlorambucil plus radiotherapy versus radiotherapy alone in low grade, localised non-Hodgkins lymphoma. Med Oncol. 1994;11(1):19-25. link to original article PubMed
TROG 99.03: MacManus M, Fisher R, Roos D, O'Brien P, Macann A, Davis S, Tsang R, Christie D, McClure B, Joseph D, Jayamohan J, Seymour JF. Randomized trial of systemic therapy after involved-field radiotherapy in patients with early-stage follicular lymphoma: TROG 99.03. J Clin Oncol. 2018 Oct 10;36(29):2918-2925. Epub 2018 Jul 5. link to original article PubMed

Advanced disease, pre-phase

Rituximab monotherapy

back to top

Regimen

Study	Evidence
Hainsworth et al. 2005a	Phase II
Hainsworth et al. 2009	Phase II

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days 1, 8, 15, 22

28-day course

Subsequent treatment

Hainsworth et al. 2005a: R-CHOP x 3 or R-CVP x 3, then Rituximab consolidation
Hainsworth et al. 2009: R-CHOP x 3, then Ibritumumab tiuxetan consolidation

References

Hainsworth JD, Litchy S, Morrissey LH, Andrews MB, Grimaldi M, McCarty M, Greco FA. Rituximab plus short-duration chemotherapy as first-line treatment for follicular non-Hodgkin's lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Mar 1;23(7):1500-6. Epub 2005 Jan 4. link to original article contains verified protocol PubMed
Hainsworth JD, Spigel DR, Markus TM, Shipley D, Thompson D, Rotman R, Dannaher C, Greco FA. Rituximab plus short-duration chemotherapy followed by yttrium-90 ibritumomab tiuxetan as first-line treatment for patients with follicular non-Hodgkin lymphoma: a phase II trial of the Sarah Cannon Oncology Research Consortium. Clin Lymphoma Myeloma. 2009 Jun;9(3):223-8. link to SD article contains verified protocol PubMed

Advanced disease, first-line therapy, randomized data

Bendamustine & Obinutuzumab

back to top

G-B: Gazyva (Obinutuzumab) & Bendamustine

Regimen

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Marcus et al. 2017 (GALLIUM)	Phase III (E-RT-switch-ic)	See link	See link	style="background-color:#d73027" \|See link

Chemotherapy

Bendamustine 90 mg/m² IV once per day on days 1 & 2
Obinutuzumab (Gazyva) as follows:
- Cycle 1: 1000 mg IV once per day on days 1, 8, 15
- Cycles 2 to 6: 1000 mg IV once on day 1

28-day cycle for 6 cycles

Subsequent treatment

Obinutuzumab maintenance

References

GALLIUM: Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. link to original article link to appendix contains verified protocol in appendix PubMed
1. Update: Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. link to original article PubMed

BR

back to top

BR: Bendamustine & Rituximab
R-B: Rituximab & Bendamustine

Variant #1, 6 cycles

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Rummel et al. 2013 (StiL NHL1)	Phase III (E-de-esc)	R-CHOP	Superior PFS
Marcus et al. 2017 (GALLIUM)	Phase III (C)	See link	See link	See link
Morschhauser et al. 2018 (RELEVANCE)	Phase III (C)	Lenalidomide & Rituximab	Did not meet primary endpoints of CR rate/PFS	Different toxicity

Chemotherapy

Bendamustine 90 mg/m² IV once per day on days 1 & 2
Rituximab (Rituxan) 375 mg/m² IV once on day 1

Supportive medications

Antiemetics, antipyretics, and antibiotics according to local standard of care
Prophylactic use of G-CSF allowed according ASCO guidelines (2006)

28-day cycle for up to 6 cycles

Subsequent treatment

GALLIUM & RELEVANCE: Rituximab maintenance

Variant #2, 6 cycles with rituximab extension

Study	Evidence
Rummel et al. 2014 (MAINTAIN)	Non-randomized portion of RCT

Chemotherapy

Bendamustine as follows:
- Cycles 1 to 6: 90 mg/m² IV once per day on days 1 & 2
- Cycles 7 & 8: none
Rituximab (Rituxan) 375 mg/m² IV once on day 1

28-day cycle for 8 cycles

Subsequent treatment

Rituximab maintenance x 2 y versus rituximab maintenance x 4 y

Variant #3, 8 cycles

Study	Evidence	Comparator	Comparative Efficacy
Flinn et al. 2014 (BRIGHT)	Phase III (E-de-esc)	1. R-CHOP 2. R-CVP	Superior PFS (*)

Efficacy in BRIGHT is based on the 2019 update. Patients in BRIGHT were required to be treatment-naive with a need for treatment per any of the following: B symptoms, large tumor mass (lymphomas with a diameter greater than 3 cm in 3 or more regions or diameter greater than 7 cm in 1 region), presence of lymphoma-related complications, or hyperviscosity syndrome attributed to monoclonal gammopathy.

Chemotherapy

Bendamustine 90 mg/m² IV once per day on days 1 & 2
Rituximab (Rituxan) 375 mg/m² IV once on day 1

Supportive medications

Antiemetics, antipyretics, and antibiotics according to local standard of care
Prophylactic use of G-CSF allowed according ASCO guidelines (2006)

28-day cycle for up to 8 cycles

References

StiL NHL1: Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Dürk H, Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W; Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013 Apr 6;381(9873):1203-10. Epub 2013 Feb 20. Erratum in: Lancet. 2013 Apr 6;381(9873):1184. link to original article contains verified protocol PubMed
1. Update: Abstract: Mathias J. Rummel, MD, Georg Maschmeyer, MD, Arnold Ganser, Andrea Heider, PhD, Ulrich von Grünhagen, MD, PhD5, Christoph Losem, Gerhard Heil, MD, Manfred Welslau, Christina Balser, MD, Ulrich Kaiser, MD, Eckhart Weidmann, Heinz Dürk, MD, Hans Peter Böck, Martina Beate Stauch, MD, Jürgen Barth, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Axel Hinke, PhD and Wolfram Brugger, MD. Bendamustine Plus Rituximab (B-R) Versus CHOP Plus Rituximab (CHOP-R) As First-Line Treatment in Patients with Indolent and Mantle Cell Lymphomas (MCL) – 7 Year Updated Results from the StiL NHL1 Study. Blood 2014 124:4407. link to abstract
2. Update: Abstract: Mathias J. Rummel, Georg Maschmeyer, Arnold Ganser, Andrea Heider, Ulrich von Gruenhagen, Christoph Losem, Gerhard Heil, Manfred Welslau, Christina Balser, Ulrich Kaiser, Eckhart Weidmann, Heinz Albert Dürk, Harald Ballo, Martina Stauch, Wolfgang Blau, Alexander Burchardt, Juergen Barth, Frank Kauff, and Wolfram Brugger. Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent lymphomas: Nine-year updated results from the StiL NHL1 study. Journal of Clinical Oncology 2017 35:15_suppl, 7501-7501 link to abstract
BRIGHT: Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. link to original article contains verified protocol link to PMC article PubMed
1. Update: Flinn IW, van der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, Simpson D, Kolibaba K, Issa S, Chang J, Trotman J, Hallman D, Chen L, Burke JM. First-line treatment of patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma with bendamustine plus rituximab versus R-CHOP or R-CVP: results of the BRIGHT 5-year follow-up study. J Clin Oncol. 2019 Apr 20;37(12):984-991. Epub 2019 Feb 27. link to original article link to PMC article PubMed
Abstract: Mathias J. Rummel, MD, Andreas Viardot, Richard Greil, MD, Bernd Hertenstein, MD, Christian Lerchenmüller, MD, Arnold Ganser, Manfred Reeb, MD, Ulrich Kaiser, MD, Christina Balser, MD, Georg Maschmeyer, MD, Heinz Dürk, MD, Georg Schliesser, MD, Tobias Gaska, MD, Jan Dürig, MD, Axel C. Matzdorff, MD, Rudolf Weide, MD, Axel Hinke, PhD, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Jürgen Barth and Wolfram Brugger, MD. Bendamustine Plus Rituximab Followed By Rituximab Maintenance for Patients with Untreated Advanced Follicular Lymphomas. Results from the StiL NHL 7-2008 Trial (MAINTAIN trial) (ClinicalTrials.gov Identifier: NCT00877214). Blood 2014 124:3052 link to abstract
GALLIUM: Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. link to original article link to appendix contains verified protocol in appendix PubMed
1. Update: Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. link to original article PubMed
RELEVANCE: Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. link to original article contains verified protocol in supplement PubMed

Chlorambucil monotherapy

back to top

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Ardeshna et al. 2003	Phase III (C)	Observation	Did not meet primary endpoint of OS

This is the comparator arm to the "watch and wait" strategy, and is not commonly used.

Chemotherapy

Chlorambucil (Leukeran) 10 mg PO once per day

Continued indefinitely

References

Ardeshna KM, Smith P, Norton A, Hancock BW, Hoskin PJ, MacLennan KA, Marcus RE, Jelliffe A, Vaughan G, Hudson GV, Linch DC; British National Lymphoma Investigation. Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial. Lancet. 2003 Aug 16;362(9383):516-22. link to original article contains verified protocol PubMed

Cyclophosphamide monotherapy

back to top

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Peterson et al. 2003 (CALGB 7951)	Phase III (E-de-esc)	CHOP-B	Did not meet primary endpoint of OS
Smith et al. 2009 (CALGB 8691)	Phase III (C)	Cyclophosphamide & Interferon alfa-2a	Did not meet primary endpoint of EFS

Note: this is an experimental arm that did not meet its primary endpoint; included here because it was eventually used to establish this regimen as a standard comparator.

Chemotherapy

Cyclophosphamide (Cytoxan) 100 mg/m² PO once per day
- Dose modifications according to WBC and platelet count as listed in Table 1 of Peterson et al. 2003

Treatment continued in responders for 2 years beyond maximal response

References

CALGB 7951: Peterson BA, Petroni GR, Frizzera G, Barcos M, Bloomfield CD, Nissen NI, Hurd DD, Henderson ES, Sartiano GP, Johnson JL, Holland JF, Gottlieb AJ. Prolonged single-agent versus combination chemotherapy in indolent follicular lymphomas: a study of the Cancer and Leukemia Group B. J Clin Oncol. 2003 Jan 1;21(1):5-15. link to original article contains verified protocol PubMed
CALGB 8691: Smith SM, Johnson J, Cheson BD, Canellos G, Petroni G, Oken M, Duggan D, Hurd D, Gockerman JP, Parker B, Prchal J, Peterson BA; Cancer and Leukemia Group B; Eastern Cooperative Oncology Group. Recombinant interferon-alpha2b added to oral cyclophosphamide either as induction or maintenance in treatment-naive follicular lymphoma: final analysis of CALGB 8691. Leuk Lymphoma. 2009 Oct;50(10):1606-17. link to original article link to PMC article PubMed

G-CVP

back to top

G-CVP: Gazyva (Obinutuzumab), Cyclophosphamide, Vincristine, Prednisone

Regimen

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Marcus et al. 2017 (GALLIUM)	Phase III (E-RT-switch-ic)	See link	See link	style="background-color:#d73027" \|See link

Note: Patients received obinutuzumab only in cycles 7 & 8.

Chemotherapy

Obinutuzumab (Gazyva) as follows:
- Cycle 1: 1000 mg IV once per day on days 1, 8, 15
- Cycles 2 to 8: 1000 mg IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for 8 cycles

Subsequent treatment

Obinutuzumab maintenance

References

GALLIUM: Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. link to original article link to appendix contains verified protocol in appendix PubMed
1. Update: Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. link to original article PubMed

G-CHOP

back to top

G-CHOP: Gazyva (Obinutuzumab), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne

Regimen

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Marcus et al. 2017 (GALLIUM)	Phase III (E-RT-switch-ic)	See link	See link	style="background-color:#d73027" \|See link

Note: Patients received obinutuzumab only in cycles 7 & 8.

Chemotherapy

Obinutuzumab (Gazyva) as follows:
- Cycle 1: 1000 mg IV once per day on days 1, 8, 15
- Cycles 2 to 8: 1000 mg IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for 8 cycles

Subsequent treatment

Obinutuzumab maintenance

References

GALLIUM: Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. link to original article link to appendix contains verified protocol in appendix PubMed
1. Update: Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. link to original article PubMed

Lenalidomide & Rituximab

back to top

R²: Rituximab & Revlimid (Lenalidomide)

Variant #1

Study	Evidence	Comparator	Comparative Efficacy
Zucca et al. 2019 (SAKK 35/10)	Randomized Phase II (E-esc)	Rituximab	Might have superior CR/CRu rate

Chemotherapy

Lenalidomide (Revlimid) 15 mg PO once per day, starting 14 days prior to first rituximab infusion and continuing until 14 days past last rituximab infusion
Rituximab (Rituxan) as follows:
- Cycles 1 & 3: 375 mg/m² IV once per day on days 1, 8, 15, 22

28-day cycle for 4 cycles

Variant #2

Study	Evidence
Fowler et al. 2014	Phase II

Chemotherapy

Lenalidomide (Revlimid) 20 mg PO once per day on days 1 to 21
Rituximab (Rituxan) 375 mg/m² IV once on day 1

28-day cycle for up to 12 cycles

Variant #3

Study	Evidence
Martin et al. 2017 (CALGB 50803)	Phase II

Chemotherapy

Lenalidomide (Revlimid) 20 mg PO once per day on days 1 to 21
Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22
- Cycles 4, 6, 8, 10: 375 mg/m² IV once on day 1

28-day cycle for 12 cycles

Variant #4

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Morschhauser et al. 2018 (RELEVANCE)	Phase III (E-switch-ooc)	1. R-B 2. R-CHOP 3. R-CVP	Did not meet primary endpoints of CR rate/PFS	Different toxicity

Chemotherapy

Lenalidomide (Revlimid) 20 mg PO once per day on days 2 to 22
Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22
- Cycles 2 to 6: 375 mg/m² IV once on day 1

28-day cycle for 6 cycles

Subsequent treatment

Responders: Lenalidomide & Rituximab maintenance

References

Fowler NH, Davis RE, Rawal S, Nastoupil L, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale MA, Fayad LE, Westin JR, Shah J, Orlowski RZ, Wang M, Turturro F, Oki Y, Claret LC, Feng L, Baladandayuthapani V, Muzzafar T, Tsai KY, Samaniego F, Neelapu SS. Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial. Lancet Oncol. 2014 Nov;15(12):1311-8. Epub 2014 Oct 15. link to original article contains protocol link to PMC article PubMed
SAKK 35/10: Zucca E, Rondeau S, Vanazzi A, Østenstad B, Mey UJM, Rauch D, Wahlin BE, Hitz F, Hernberg M, Johansson AS, de Nully Brown P, Hagberg H, Ferreri AJM, Lohri A, Novak U, Zander T, Bersvendsen H, Bargetzi M, Mingrone W, Krasniqi F, Dirnhofer S, Hayoz S, Hawle H, Vilei SB, Ghielmini M, Kimby E; Swiss Group for Clinical Cancer Research and the Nordic Lymphoma Group. Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy. Blood. 2019 Jul 25;134(4):353-362. Epub 2019 May 17. link to original article PubMed
CALGB 50803: Martin P, Jung SH, Pitcher B, Bartlett NL, Blum KA, Shea T, Hsi ED, Ruan J, Smith SE, Leonard JP, Cheson BD. A phase II trial of lenalidomide plus rituximab in previously untreated follicular non-Hodgkin's lymphoma (NHL): CALGB 50803 (Alliance). Ann Oncol. 2017 Nov 1;28(11):2806-2812. link to original article contains protocol PubMed
RELEVANCE: Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. link to original article contains verified protocol PubMed

Observation

back to top

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Horning & Rosenberg 1984	Non-randomized
Young et al. 1988	Phase III (E-de-esc)	ProMACE-MOPP, then TNI
Brice et al. 1997	Phase III (E-de-esc)	1. Interferon alfa 2. Prednimustine	Did not meet primary endpoint of OS
Ardeshna et al. 2003	Phase III (E-de-esc)	Chlorambucil	Did not meet primary endpoint of OS
Ardeshna et al. 2014 (CRUK-2004-001621-16)	Phase III (C)	1. Rituximab induction	Inferior TTNT
Ardeshna et al. 2014 (CRUK-2004-001621-16)	Phase III (C)	2. Rituximab induction, then Rituximab maintenance	Inferior TTNT

Also known as "watchful waiting".

References

Horning SJ, Rosenberg SA. The natural history of initially untreated low-grade non-Hodgkin's lymphomas. N Engl J Med. 1984 Dec 6;311(23):1471-5. link to original article PubMed
Young RC, Longo DL, Glatstein E, Ihde DC, Jaffe ES, DeVita VT Jr. The treatment of indolent lymphomas: watchful waiting v aggressive combined modality treatment. Semin Hematol. 1988 Apr;25(2 Suppl 2):11-6. PubMed
Brice P, Bastion Y, Lepage E, Brousse N, Haïoun C, Moreau P, Straetmans N, Tilly H, Tabah I, Solal-Céligny P. Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d'Etude des Lymphomes Folliculaires; Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 1997 Mar;15(3):1110-7. link to original article PubMed
Ardeshna KM, Smith P, Norton A, Hancock BW, Hoskin PJ, MacLennan KA, Marcus RE, Jelliffe A, Vaughan G, Hudson GV, Linch DC; British National Lymphoma Investigation. Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial. Lancet. 2003 Aug 16;362(9383):516-22. link to original article PubMed
CRUK-2004-001621-16: Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P, Warden J, Stevens L, Pocock CF, Miall F, Cunningham D, Davies J, Jack A, Stephens R, Walewski J, Ferhanoglu B, Bradstock K, Linch DC. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol. 2014 Apr;15(4):424-35. Epub 2014 Mar 4. link to original article PubMed

R-CHOP

back to top

R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Variant #1, 3 cycles with prednisone 100 mg

Study	Evidence
Hainsworth et al. 2005a	Phase II
Hainsworth et al. 2009	Phase II

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Preceding treatment

Rituximab pre-phase x 4

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for 3 cycles

Subsequent treatment

Hainsworth et al. 2005a: Rituximab consolidation
Hainsworth et al. 2009: Ibritumumab tiuxetan consolidation, in 4 weeks

Variant #2, 3 cycles with prednisone 100 mg/m²

Study	Evidence
Jacobs et al. 2008	Phase II

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. R-CHOP given as per standard ECOG dosing, except that rituximab is given on day 1 of each cycle:

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg/m² PO once per day on days 1 to 5

Supportive medications

Filgrastim (Neupogen) "recommended according to guidelines"

21-day cycle for 3 cycles

Subsequent treatment

Ibritumumab tiuxetan consolidation

Variant #3, prednisone 100 mg

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Salles et al. 2010 (PRIMA)	Non-randomized portion of RCT
Flinn et al. 2014 (BRIGHT)	Phase III (C)	BR	Seems to have non-inferior CR rate
Marcus et al. 2017 (GALLIUM)	Phase III (C)	See link	See link	See link
Morschhauser et al. 2018 (RELEVANCE)	Phase III (C)	Lenalidomide & Rituximab	Did not meet primary endpoints of CR rate/PFS	Different toxicity

In PRIMA, initial therapy was investigator's choice. Patients in BRIGHT were required to be treatment-naive with a need for treatment per any of the following: B symptoms, large tumor mass (lymphomas with a diameter greater than 3 cm in 3 or more regions or diameter greater than 7 cm in 1 region), presence of lymphoma-related complications, or hyperviscosity syndrome attributed to monoclonal gammopathy. Patients in GALLIUM & RELEVANCE received rituximab only in cycles 7 & 8.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

Supportive medications

Antiemetics, antipyretics, and antibiotics per local standard of care
G-CSF "according to the American Society of Clinical Oncology guidelines"

21-day cycle for 6 to 8 cycles (see note)

Subsequent treatment

PRIMA, responders (PR or CR): Maintenance rituximab versus no further treatment
GALLIUM & RELEVANCE: Maintenance rituximab

Variant #4, prednisone 100 mg/m²

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Hiddemann et al. 2005 (GLSG '00)	Phase III (E-esc)	CHOP	Seems to have superior OS	Increased toxicity
Federico et al. 2013 (FOLL05)	Phase III (E-esc)	1. R-CVP	Seems to have superior PFS
Federico et al. 2013 (FOLL05)	Phase III (E-esc)	2. R-FM	Did not meet primary endpoint of TTF

In FOLL05, PFS was superior to R-CVP but equivalent to R-FM; risk/benefit ratio was better than R-FM. Patients in FOLL05 received a total of 8 doses of rituximab, regardless of the number of CHOP cycles.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on either day 1 or day -1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg/m² PO once per day on days 1 to 5

21-day cycle for 6 to 8 cycles

Variant #5, variant rituximab schedule

Study	Evidence	Comparator	Comparative Efficacy
Czuczman et al. 1999	Phase II
Press et al. 2012 (SWOG S0016)	Phase III (C)	CHOP, then ¹³¹Iodine-Tositumomab	Inferior PFS (*)

In SWOG S0016, this regimen was intended for patients greater than 18 years with untreated bulky stage II or stage III-IV FL (all grades) expressing CD20. Reported efficacy for SWOG S0016 is based on the 2018 update.

Chemotherapy

Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days -7 & -2
- Cycles 3 & 5: 375 mg/m² IV once on day -2
- Cycle 6*: 375 mg/m² IV once per day 8 days and 15 days after completion of cycle 6 (i.e., what would be cycle 7 days 8 & 15)
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg/m² PO once per day on days 1 to 5

21-day cycle for 6 cycles

Variant #6, 4 doses of rituximab

Study	Evidence	Comparator	Comparative Efficacy
Watanabe et al. 2011 (JCOG 0203)	Phase III (C)	R-CHOP-14	Did not meet primary endpoint of PFS

This regimen was intended for patients with previously untreated stage III to IV indolent B-cell NHL, including FL grade 3B.

Chemotherapy

Rituximab (Rituxan) as follows:
- Cycles 1, 2, 4, 6: 375 mg/m² IV once on day -2
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

Supportive medications

G-CSF "according to the [2000] American Society of Clinical Oncology guidelines," i.e., generally no routine use except for patients at high risk (>40%) for febrile neutropenia due to special circumstances

21-day cycle for 6 cycles

References

Czuczman MS, Grillo-López AJ, White CA, Saleh M, Gordon L, LoBuglio AF, Jonas C, Klippenstein D, Dallaire B, Varns C. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol. 1999 Jan;17(1):268-76. link to original article contains protocol PubMed
1. Update: Czuczman MS, Weaver R, Alkuzweny B, Berlfein J, Grillo-López AJ. Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin's lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol. 2004 Dec 1;22(23):4711 to 6. Epub 2004 Oct 13. link to original article PubMed
Hainsworth JD, Litchy S, Morrissey LH, Andrews MB, Grimaldi M, McCarty M, Greco FA. Rituximab plus short-duration chemotherapy as first-line treatment for follicular non-Hodgkin's lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Mar 1;23(7):1500-6. Epub 2005 Jan 4. link to original article contains verified protocol PubMed
GLSG '00: Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, Reiser M, Metzner B, Harder H, Hegewisch-Becker S, Fischer T, Kropff M, Reis HE, Freund M, Wörmann B, Fuchs R, Planker M, Schimke J, Eimermacher H, Trümper L, Aldaoud A, Parwaresch R, Unterhalt M. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005 Dec 1;106(12):3725-32. Epub 2005 Aug 25. link to original article contains protocol PubMed
Jacobs SA, Swerdlow SH, Kant J, Foon KA, Jankowitz R, Land SR, DeMonaco N, Joyce J, Osborn JL, Evans TL, Schaefer PM, Luong TM. Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Clin Cancer Res. 2008 Nov 1;14(21):7088-94. link to original article contains verified protocol PubMed
Hainsworth JD, Spigel DR, Markus TM, Shipley D, Thompson D, Rotman R, Dannaher C, Greco FA. Rituximab plus short-duration chemotherapy followed by yttrium-90 ibritumomab tiuxetan as first-line treatment for patients with follicular non-Hodgkin lymphoma: a phase II trial of the Sarah Cannon Oncology Research Consortium. Clin Lymphoma Myeloma. 2009 Jun;9(3):223-8. link to SD article contains verified protocol PubMed
PRIMA: Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. link to original article contains protocol PubMed
1. QoL Analysis: Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. link to original article PubMed
2. Update: Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. link to original article link to PMC article PubMed
JCOG 0203: Watanabe T, Tobinai K, Shibata T, Tsukasaki K, Morishima Y, Maseki N, Kinoshita T, Suzuki T, Yamaguchi M, Ando K, Ogura M, Taniwaki M, Uike N, Takeuchi K, Nawano S, Terauchi T, Hotta T. Phase II/III study of R-CHOP-21 versus R-CHOP-14 for untreated indolent B-cell non-Hodgkin's lymphoma: JCOG 0203 trial. J Clin Oncol. 2011 Oct 20;29(30):3990-8. Epub 2011 Sep 19. link to original article contains verified protocol PubMed
1. Update: Watanabe T, Tobinai K, Wakabayashi M, Morishima Y, Kobayashi H, Kinoshita T, Suzuki T, Yamaguchi M, Ando K, Ogura M, Taniwaki M, Uike N, Yoshino T, Nawano S, Terauchi T, Hotta T, Nagai H, Tsukasaki K; JCOG0203 Collaborators. Outcomes after R-CHOP in patients with newly diagnosed advanced follicular lymphoma: a 10-year follow-up analysis of the JCOG0203 trial. Lancet Haematol. 2018 Nov;5(11):e520-e531. link to original article PubMed
SWOG S0016: Press OW, Unger JM, Rimsza LM, Friedberg JW, LeBlanc M, Czuczman MS, Kaminski M, Braziel RM, Spier C, Gopal AK, Maloney DG, Cheson BD, Dakhil SR, Miller TP, Fisher RI. Phase III randomized intergroup trial of CHOP plus rituximab compared with CHOP chemotherapy plus 131Iodine-tositumomab for previously untreated follicular non-Hodgkin lymphoma: SWOG S0016. J Clin Oncol. 2013 Jan 20;31(3):314-20. Epub 2012 Dec 10. link to original article link to PMC article PubMed
1. Update: Shadman M, Li H, Rimsza L, Leonard JP, Kaminski MS, Braziel RM, Spier CM, Gopal AK, Maloney DG, Cheson BD, Dakhil S, LeBlanc M, Smith SM, Fisher RI, Friedberg JW, Press OW. Continued excellent outcomes in previously untreated patients with follicular lymphoma after treatment with CHOP plus rituximab or CHOP plus (131)I-tositumomab: long-term follow-up of phase III randomized study SWOG-S0016. J Clin Oncol. 2018 Mar 1;36(7):697-703. Epub 2018 Jan 22. link to original article PubMed
StiL NHL1: Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Dürk H, Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W; Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013 Apr 6;381(9873):1203-10. Epub 2013 Feb 20. Erratum in: Lancet. 2013 Apr 6;381(9873):1184. link to original article PubMed
1. Update: Abstract: Mathias J. Rummel, MD, Georg Maschmeyer, MD, Arnold Ganser, Andrea Heider, PhD, Ulrich von Grünhagen, MD, PhD5, Christoph Losem, Gerhard Heil, MD, Manfred Welslau, Christina Balser, MD, Ulrich Kaiser, MD, Eckhart Weidmann, Heinz Dürk, MD, Hans Peter Böck, Martina Beate Stauch, MD, Jürgen Barth, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Axel Hinke, PhD and Wolfram Brugger, MD. Bendamustine Plus Rituximab (B-R) Versus CHOP Plus Rituximab (CHOP-R) As First-Line Treatment in Patients with Indolent and Mantle Cell Lymphomas (MCL) – 7 Year Updated Results from the StiL NHL1 Study. Blood 2014 124:4407. link to abstract
2. Update: Abstract: Mathias J. Rummel, Georg Maschmeyer, Arnold Ganser, Andrea Heider, Ulrich von Gruenhagen, Christoph Losem, Gerhard Heil, Manfred Welslau, Christina Balser, Ulrich Kaiser, Eckhart Weidmann, Heinz Albert Dürk, Harald Ballo, Martina Stauch, Wolfgang Blau, Alexander Burchardt, Juergen Barth, Frank Kauff, and Wolfram Brugger. Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent lymphomas: Nine-year updated results from the StiL NHL1 study. Journal of Clinical Oncology 2017 35:15_suppl, 7501-7501 link to abstract
FOLL05: Federico M, Luminari S, Dondi A, Tucci A, Vitolo U, Rigacci L, Di Raimondo F, Carella AM, Pulsoni A, Merli F, Arcaini L, Angrilli F, Stelitano C, Gaidano G, Dell'olio M, Marcheselli L, Franco V, Galimberti S, Sacchi S, Brugiatelli M. R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage follicular lymphoma: results of the FOLL05 trial conducted by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Apr 20;31(12):1506-13. Epub 2013 Mar 25. Erratum in: J Clin Oncol. 2014 Apr 1;32(10):1095. Dosage error in article text. link to original article contains verified protocol PubMed
1. Update: Luminari S, Ferrari A, Manni M, Dondi A, Chiarenza A, Merli F, Rusconi C, Tarantino V, Tucci A, Vitolo U, Kovalchuk S, Angelucci E, Pulsoni A, Arcaini L, Angrilli F, Gaidano G, Stelitano C, Bertoldero G, Cascavilla N, Salvi F, Ferreri AJM, Vallisa D, Marcheselli L, Federico M. Long-term results of the FOLL05 trial comparing R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage symptomatic follicular lymphoma. J Clin Oncol. 2018 Mar 1;36(7):689-696. Epub 2017 Nov 2. link to original article PubMed
Abstract: Armando Lopez-Guillermo, MD, PhD, Miguel A. Canales, MD, PhD, Ivan Dlouhy, Javier Briones, MD, Dolores Caballero, MD, PhD, Juan Manuel Sancho Sr., MD, Santiago Mercadal Vilchez, MD, Jose María Moraleda, MD, María José Terol, MD, PhD, Antonio Salar, MD, Luis Palomera, MD, Santiago Gardella, MD, Isidro Jarque, MD, Secundino Ferrer, Joan Bargay, MD, Andres Lopez, Carlos Panizo, Anna Muntanola, MD, Carlos Montalban, Eulogio Conde, MD, PhD, Miguel Hernandez, MD, Alfons Soler, Julian Marin, MD, Jose García Marco, Guillermo Deben and José Francisco Tomas, MD, PhD. A Randomized Phase II Study Comparing Consolidation With a Single Dose Of 90y Ibritumomab Tiuxetan (Zevalin®) (Z) Vs. Maintenance With Rituximab (R) For Two Years In Patients With Newly Diagnosed Follicular Lymphoma (FL) Responding To R-CHOP. Preliminary Results At 36 Months From Randomization. Blood 2013 122:369. link to abstract
BRIGHT: Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. link to original article contains verified protocol link to PMC article PubMed
1. Update: Flinn IW, van der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, Simpson D, Kolibaba K, Issa S, Chang J, Trotman J, Hallman D, Chen L, Burke JM. First-line treatment of patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma with bendamustine plus rituximab versus R-CHOP or R-CVP: results of the BRIGHT 5-year follow-up study. J Clin Oncol. 2019 Apr 20;37(12):984-991. Epub 2019 Feb 27. link to original article link to PMC article PubMed
GALLIUM: Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. link to original article link to appendix contains verified protocol in appendix PubMed
1. Update: Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. link to original article PubMed
RELEVANCE: Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. link to original article contains verified protocol in supplement PubMed

R-CHVP+I

back to top

R-CHVP+I: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), VP-16 (Etoposide), Prednisolone, Interferon-a2a

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Salles et al. 2008 (FL2000)	Phase III (E-esc)	CHVP+I	Superior EFS

Chemotherapy

Rituximab (Rituxan) as follows:
- Cycles 3 & 4: 375 mg/m² IV once per day on days 1 and 8
- Cycles 5 & 6: 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 600 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 25 mg/m² IV once on day 1
Etoposide (Vepesid) 100 mg/m² IV once on day 1
Prednisolone (Millipred) 40 mg/m² PO once per day on days 1 to 5

28-day cycle for 6 cycles

Subsequent treatment

Interferon alfa-2a maintenance

References

FL2000: Salles G, Mounier N, de Guibert S, Morschhauser F, Doyen C, Rossi JF, Haioun C, Brice P, Mahé B, Bouabdallah R, Audhuy B, Ferme C, Dartigeas C, Feugier P, Sebban C, Xerri L, Foussard C. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood. 2008 Dec 15;112(13):4824-31. Epub 2008 Sep 17. link to original article contains verified protocol PubMed
1. Update: Bachy E, Houot R, Morschhauser F, Sonet A, Brice P, Belhadj K, Cartron G, Audhuy B, Fermé C, Feugier P, Sebban C, Delwail V, Maisonneuve H, Le Gouill S, Lefort S, Brousse N, Foussard C, Salles G; Groupe d'Etude des Lymphomes de l'Adulte (GELA). Long-term follow up of the FL2000 study comparing CHVP-interferon to CHVP-interferon plus rituximab in follicular lymphoma. Haematologica. 2013 Jul;98(7):1107-14. Epub 2013 May 3. link to original article link to PMC article PubMed

R-CVP

back to top

R-CVP: Rituximab, Cyclophosphamide, Vincristine, Prednisone

Variant #1, prednisone 40 mg/m²

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Marcus et al. 2005	Phase III (E-RT-esc)	CVP	Superior TTP	Similar toxicity
Salles et al. 2010 (PRIMA)	Non-randomized portion of RCT
Federico et al. 2013 (FOLL05)	Phase III (E-de-esc)	1. R-CHOP	Seems to have inferior PFS	See paper
Federico et al. 2013 (FOLL05)	Phase III (E-de-esc)	2. R-FM	Inferior PFS (*)	See paper
Morschhauser et al. 2018 (RELEVANCE)	Phase III (C)	Lenalidomide & Rituximab	Did not meet primary endpoints of CR rate/PFS	Different toxicity

Note: reported efficacy for FOLL05 for comparison marked with (*) is based on the 2017 update.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 5

21-day cycle for up to 8 cycles

Subsequent treatment

PRIMA, responders (PR or CR): Rituximab maintenance versus no further treatment
RELEVANCE, responders: Rituximab maintenance

Variant #2, prednisone 100 mg/day

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Flinn et al. 2014 (BRIGHT)	Phase III (C)	BR	Seems to have non-inferior CR rate
Marcus et al. 2017 (GALLIUM)	Phase III (C)	See link	See link	See link

Patients in BRIGHT were required to be treatment-naive with a need for treatment per any of the following: B symptoms, large tumor mass (lymphomas with a diameter greater than 3 cm in 3 or more regions or diameter greater than 7 cm in 1 region), presence of lymphoma-related complications, or hyperviscosity syndrome attributed to monoclonal gammopathy. Patients in GALLIUM received rituximab only in cycles 7 & 8.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
- BRIGHT: patients could receive 1000 mg/m² IV once on day 1, instead
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

Supportive medications

Antiemetics, antipyretics, and antibiotics per local standard of care
G-CSF "according to the American Society of Clinical Oncology guidelines"

21-day cycle for up to 8 cycles

Subsequent treatment

GALLIUM: Rituximab maintenance

Variant #3, 3 cycles

Study	Evidence
Hainsworth et al. 2005a	Phase II

Preceding treatment

Rituximab pre-phase x 4

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 1000 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for 3 cycles

Subsequent treatment

Rituximab consolidation

References

Hainsworth JD, Litchy S, Morrissey LH, Andrews MB, Grimaldi M, McCarty M, Greco FA. Rituximab plus short-duration chemotherapy as first-line treatment for follicular non-Hodgkin's lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Mar 1;23(7):1500-6. Epub 2005 Jan 4. link to original article contains verified protocol PubMed
Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J, Solal-Celigny P, Offner F, Walewski J, Raposo J, Jack A, Smith P. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005 Feb 15;105(4):1417-23. link to original article contains protocol PubMed
1. Update: Marcus R, Imrie K, Solal-Celigny P, Catalano JV, Dmoszynska A, Raposo JC, Offner FC, Gomez-Codina J, Belch A, Cunningham D, Wassner-Fritsch E, Stein G. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol. 2008 Oct 1;26(28):4579-86. Epub 2008 Jul 28. link to original article PubMed
PRIMA: Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. link to original article contains protocol PubMed
1. QoL Analysis: Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. link to original article PubMed
2. Update: Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. link to original article link to PMC article PubMed
FOLL05: Federico M, Luminari S, Dondi A, Tucci A, Vitolo U, Rigacci L, Di Raimondo F, Carella AM, Pulsoni A, Merli F, Arcaini L, Angrilli F, Stelitano C, Gaidano G, Dell'olio M, Marcheselli L, Franco V, Galimberti S, Sacchi S, Brugiatelli M. R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage follicular lymphoma: results of the FOLL05 trial conducted by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Apr 20;31(12):1506-13. Epub 2013 Mar 25. Erratum in: J Clin Oncol. 2014 Apr 1;32(10):1095. Dosage error in article text. link to original article contains verified protocol PubMed
1. Update: Luminari S, Ferrari A, Manni M, Dondi A, Chiarenza A, Merli F, Rusconi C, Tarantino V, Tucci A, Vitolo U, Kovalchuk S, Angelucci E, Pulsoni A, Arcaini L, Angrilli F, Gaidano G, Stelitano C, Bertoldero G, Cascavilla N, Salvi F, Ferreri AJM, Vallisa D, Marcheselli L, Federico M. Long-term results of the FOLL05 trial comparing R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage symptomatic follicular lymphoma. J Clin Oncol. 2018 Mar 1;36(7):689-696. Epub 2017 Nov 2. link to original article PubMed
BRIGHT: Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. link to original article contains verified protocol link to PMC article PubMed
1. Update: Flinn IW, van der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, Simpson D, Kolibaba K, Issa S, Chang J, Trotman J, Hallman D, Chen L, Burke JM. First-line treatment of patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma with bendamustine plus rituximab versus R-CHOP or R-CVP: results of the BRIGHT 5-year follow-up study. J Clin Oncol. 2019 Apr 20;37(12):984-991. Epub 2019 Feb 27. link to original article link to PMC article PubMed
GALLIUM: Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. link to original article link to appendix contains verified protocol in appendix PubMed
1. Update: Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. link to original article PubMed
RELEVANCE: Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. link to original article contains verified protocol in supplement PubMed

R-FM

back to top

R-FM: Rituximab, Fludarabine, Mitoxantrone
FMR: Fludarabine, Mitoxantrone, Rituximab

Variant #1, 4 cycles

Study	Evidence
Zinzani et al. 2011	Phase II

Chemotherapy

Fludarabine (Fludara) 25 mg/m² IV once per day on days 2 to 4
Mitoxantrone (Novantrone) 10 mg/m² IV once on day 2
Rituximab (Rituxan) 375 mg/m² IV once on day 1

Supportive medications

No prophylactic use of G-CSF, but patients with grade 3 or 4 neutropenia or delayed neutropenic fever could be given growth factors for later cycles at physician discretion

28-day cycle for 4 cycles

Subsequent treatment

Patients were restaged 2 to 3 weeks after finishing cycle 4. People with at least a partial response (PR), ANC greater than 1500/uL, platelet count greater than 100 x 10⁹/L, and less than 25% bone marrow involvement were eligible for consolidation therapy with ibritumomab tiuxetan, given within 12 weeks (paper does not specify "within 12 weeks" of what)

Variant #2, 8 cycles

Study	Evidence	Comparator	Comparative Efficacy
Federico et al. 2013 (FOLL05)	Phase III (E-switch-ic)	1. R-CHOP	Did not meet primary endpoint of TTF
Federico et al. 2013 (FOLL05)	Phase III (E-switch-ic)	2. R-CVP	Superior PFS (*)

Note: risk/benefit ratio was worse than R-CHOP. Reported efficacy for comparison marked with (*) is based on the 2017 update.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Fludarabine (Fludara) as follows:
- Cycles 1 to 6: 25 mg/m² IV once per day on days 1 to 3
Mitoxantrone (Novantrone) as follows:
- Cycles 1 to 6: 10 mg/m² IV once on day 1

21-day cycle for 8 cycles

References

Zinzani PL, Tani M, Pulsoni A, De Renzo A, Stefoni V, Broccoli A, Montini GC, Fina M, Pellegrini C, Gandolfi L, Cavalieri E, Torelli F, Scopinaro F, Argnani L, Quirini F, Derenzini E, Rossi M, Pileri S, Fanti S, Baccarani M. A phase II trial of short course fludarabine, mitoxantrone, rituximab followed by ⁹⁰Y-ibritumomab tiuxetan in untreated intermediate/high-risk follicular lymphoma. Ann Oncol. 2012 Feb;23(2):415-20. Epub 2011 May 2. link to original article contains verified protocol PubMed
FOLL05: Federico M, Luminari S, Dondi A, Tucci A, Vitolo U, Rigacci L, Di Raimondo F, Carella AM, Pulsoni A, Merli F, Arcaini L, Angrilli F, Stelitano C, Gaidano G, Dell'olio M, Marcheselli L, Franco V, Galimberti S, Sacchi S, Brugiatelli M. R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage follicular lymphoma: results of the FOLL05 trial conducted by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Apr 20;31(12):1506-13. Epub 2013 Mar 25. Erratum in: J Clin Oncol. 2014 Apr 1;32(10):1095. Dosage error in article text. link to original article contains verified protocol PubMed
1. Update: Luminari S, Ferrari A, Manni M, Dondi A, Chiarenza A, Merli F, Rusconi C, Tarantino V, Tucci A, Vitolo U, Kovalchuk S, Angelucci E, Pulsoni A, Arcaini L, Angrilli F, Gaidano G, Stelitano C, Bertoldero G, Cascavilla N, Salvi F, Ferreri AJM, Vallisa D, Marcheselli L, Federico M. Long-term results of the FOLL05 trial comparing R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage symptomatic follicular lymphoma. J Clin Oncol. 2018 Mar 1;36(7):689-696. Epub 2017 Nov 2. link to original article PubMed

R-FND

back to top

R-FND: Rituximab, Fludarabine, Novantrone (mitoxantrone), Dexamethasone

Regimen

Study	Evidence
Vitolo et al. 2013 (ML17638)	Non-randomized portion of RCT

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Fludarabine (Fludara) 25 mg/m² IV once per day on days 2 to 4
Mitoxantrone (Novantrone) 10 mg/m² IV once on day 2
Dexamethasone (Decadron) 10 mg (route not specified) once per day on days 2 to 4

1-month cycle for 4 cycles

Subsequent treatment

Non-progressors: Rituximab consolidation
Responders: Rituximab maintenance versus observation

References

ML17638: Vitolo U, Ladetto M, Boccomini C, Baldini L, De Angelis F, Tucci A, Botto B, Chiappella A, Chiarenza A, Pinto A, De Renzo A, Zaja F, Castellino C, Bari A, Alvarez De Celis I, Evangelista A, Parvis G, Gamba E, Lobetti-Bodoni C, Ciccone G, Rossi G. Rituximab maintenance compared with observation after brief first-line R-FND chemoimmunotherapy with rituximab consolidation in patients age older than 60 years with advanced follicular lymphoma: a phase III randomized study by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Sep 20;31(27):3351-9. Epub 2013 Aug 19. link to original article contains verified protocol PubMed
Nastoupil LJ, McLaughlin P, Feng L, Neelapu SS, Samaniego F, Hagemeister FB, Ayala A, Romaguera JE, Goy AH, Neal E, Wang M, Fayad L, Fanale MA, Oki Y, Westin JR, Rodriguez MA, Cabanillas F, Fowler NH. High ten-year remission rates following rituximab, fludarabine, mitoxantrone and dexamethasone (R-FND) with interferon maintenance in indolent lymphoma: results of a randomized study. Br J Haematol. 2017 Apr;177(2):263-270. Epub 2017 Mar 24. link to original article PubMed

R-MCP

back to top

R-MCP: Rituximab, Mitoxantrone, Chlorambucil, Prednisolone

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Herold et al. 2007 (OSHO-39)	Phase III (E-esc)	MCP	Superior OS

Note: the chlorambucil dose is written in the reference as "3 x 3 mg/m²"; total dose per day is 9 mg/m².

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Mitoxantrone (Novantrone) 8 mg/m² IV once per day on days 3 & 4
Chlorambucil (Leukeran) 3 mg/m² PO three times per day on days 3 to 7
Prednisolone (Millipred) 25 mg/m² PO once per day on days 3 to 7

28-day cycle for up to 8 cycles

Subsequent treatment

Patients who achieved a PR or CR: Interferon alfa-2a maintenance within 4 to 8 weeks of completion of chemotherapy

References

OSHO-39: Herold M, Haas A, Srock S, Neser S, Al-Ali KH, Neubauer A, Dölken G, Naumann R, Knauf W, Freund M, Rohrberg R, Höffken K, Franke A, Ittel T, Kettner E, Haak U, Mey U, Klinkenstein C, Assmann M, von Grünhagen U; East German Study Group Hematology and Oncology Study. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol. 2007 May 20;25(15):1986-92. Epub 2007 Apr 9. link to original article contains verified protocol PubMed
1. Update: Herold M, Scholz CW, Rothmann F, Hirt C, Lakner V, Naumann R. Long-term follow-up of rituximab plus first-line mitoxantrone, chlorambucil, prednisolone and interferon-alpha as maintenance therapy in follicular lymphoma. J Cancer Res Clin Oncol. 2015 Sep;141(9):1689-95. Epub 2015 Mar 25. link to original article PubMed

Rituximab monotherapy

back to top

Variant #1, 4 doses

Study	Evidence	Comparator	Comparative Efficacy
Hainsworth et al. 2000	Phase II
Colombat et al. 2001	Phase II
Hainsworth et al. 2002	Phase II
Ghielmini et al. 2004 (SAKK 35/98)	Non-randomized portion of RCT
Ardeshna et al. 2014 (CRUK-2004-001621-16)	Phase III (E-esc)	1. Observation	Superior TTNT
Ardeshna et al. 2014 (CRUK-2004-001621-16)	Phase III (E-esc)	2. Rituximab induction, then Rituximab maintenance	Did not meet primary endpoint of TTNT
Kahl et al. 2014 (RESORT)	Non-randomized portion of RCT
Taverna et al. 2015 (SAKK 35/03)	Non-randomized portion of RCT
Ogura et al. 2018 (CT-P10 3.4)	Phase III (C)	CT-P10	Equivalent ORR

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days 1, 8, 15, 22

Supportive medications

Acetaminophen (Tylenol) 650 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to Rituximab (Rituxan)
Diphenhydramine (Benadryl) 50 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to Rituximab (Rituxan)

4-week course

Subsequent treatment

Hainsworth et al. 2002 & CT-P10 3.4, SD or better: Rituximab maintenance
SAKK 35/98, SD or better: Rituximab maintenance versus no further treatment
RESORT, PR or CR: Indefinite rituximab maintenance versus salvage rituximab at time of progression
SAKK 35/03, PR or CR: Rituximab maintenance x 9 mo versus Rituximab maintenance x 5 y

Variant #2, 8 doses

Study	Evidence	Comparator	Comparative Efficacy
Kimby et al. 2015 (NLG ML16865)	Phase III (C)	Rituximab & IFN-α2a	Did not meet primary endpoint of TTF
Zucca et al. 2019 (SAKK 35/10)	Randomized Phase II (C)	Lenalidomide & Rituximab	Might have inferior CR/CRu rate

Note: only patients achieving some degree of measurable response in NLG ML16865 proceeded to the 2nd course of rituximab.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days 1, 8, 15, 22

12-week cycle for 2 cycles

References

Hainsworth JD, Burris HA 3rd, Morrissey LH, Litchy S, Scullin DC Jr, Bearden JD 3rd, Richards P, Greco FA. Rituximab monoclonal antibody as initial systemic therapy for patients with low-grade non-Hodgkin lymphoma. Blood. 2000 May 15;95(10):3052-6. link to original article PubMed
Colombat P, Salles G, Brousse N, Eftekhari P, Soubeyran P, Delwail V, Deconinck E, Haïoun C, Foussard C, Sebban C, Stamatoullas A, Milpied N, Boué F, Taillan B, Lederlin P, Najman A, Thièblemont C, Montestruc F, Mathieu-Boué A, Benzohra A, Solal-Céligny P. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation. Blood. 2001 Jan 1;97(1):101-6. link to original article contains protocol PubMed
1. Update: Colombat P, Brousse N, Salles G, Morschhauser F, Brice P, Soubeyran P, Delwail V, Deconinck E, Haioun C, Foussard C, Sebban C, Tilly H, Thieblemont C, Bergougnoux L, Lazreg F, Solal-Celigny P. Rituximab induction immunotherapy for first-line low-tumor-burden follicular lymphoma: survival analyses with 7-year follow-up. Ann Oncol. 2012 Sep;23(9):2380-5. Epub 2012 Jul 10. link to original article PubMed
Hainsworth JD, Litchy S, Burris HA 3rd, Scullin DC Jr, Corso SW, Yardley DA, Morrissey L, Greco FA. Rituximab as first-line and maintenance therapy for patients with indolent non-hodgkin's lymphoma. J Clin Oncol. 2002 Oct 15;20(20):4261-7. link to original article contains protocol PubMed
SAKK 35/98: Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. link to original article contains protocol PubMed
1. Update: Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. link to original article contains verified protocol PubMed
Meta-analysis: Vidal L, Gafter-Gvili A, Leibovici L, Dreyling M, Ghielmini M, Hsu Schmitz SF, Cohen A, Shpilberg O. Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials. J Natl Cancer Inst. 2009 Feb 18;101(4):248-55. Epub 2009 Feb 10. PubMed
CRUK-2004-001621-16: Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P, Warden J, Stevens L, Pocock CF, Miall F, Cunningham D, Davies J, Jack A, Stephens R, Walewski J, Ferhanoglu B, Bradstock K, Linch DC. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol. 2014 Apr;15(4):424-35. Epub 2014 Mar 4. link to original article contains verified protocol PubMed
ECOG E4402: Kahl BS, Hong F, Williams ME, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ. Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: Eastern Cooperative Oncology Group protocol E4402. J Clin Oncol. 2014 Oct 1;32(28):3096-102. Epub 2014 Aug 25. link to original article contains verified protocol link to PMC article PubMed
SAKK 35/10: Zucca E, Rondeau S, Vanazzi A, Østenstad B, Mey UJM, Rauch D, Wahlin BE, Hitz F, Hernberg M, Johansson AS, de Nully Brown P, Hagberg H, Ferreri AJM, Lohri A, Novak U, Zander T, Bersvendsen H, Bargetzi M, Mingrone W, Krasniqi F, Dirnhofer S, Hayoz S, Hawle H, Vilei SB, Ghielmini M, Kimby E; Swiss Group for Clinical Cancer Research and the Nordic Lymphoma Group. Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy. Blood. 2019 Jul 25;134(4):353-362. Epub 2019 May 17. link to original article PubMed
NLG ML16865: Kimby E, Östenstad B, Brown P, Hagberg H, Erlanson M, Holte H, Linden O, Johansson AS, Ahlgren T, Wader K, Wahlin BE, Delabie J, Sundström C; Nordic Lymphoma Group (NLG). Two courses of four weekly infusions of rituximab with or without interferon-α2a: final results from a randomized phase III study in symptomatic indolent B-cell lymphomas. Leuk Lymphoma. 2015;56(9):2598-607. link to original article contains verified protocol PubMed
1. Pooled Update: Lockmer S, Østenstad B, Hagberg H, Holte H, Johansson AS, Wahlin BE, Wader KF, Steen CB, Meyer P, Maisenhølder M, Smedby KE, Brown P, Kimby E. Chemotherapy-free initial treatment of advanced indolent lymphoma has durable effect with low toxicity: results from two Nordic Lymphoma Group trials with more than 10 years of follow-up. J Clin Oncol. 2018 Nov 20;36(33):3315-23. Epub 2018 Oct 4. link to original article PubMed
SAKK 35/03: Taverna C, Martinelli G, Hitz F, Mingrone W, Pabst T, Cevreska L, Del Giglio A, Vanazzi A, Laszlo D, Raats J, Rauch D, Vorobiof DA, Lohri A, Biaggi Rudolf C, Rondeau S, Rusterholz C, Heijnen IA, Zucca E, Ghielmini M. Rituximab maintenance for a maximum of 5 years after single-agent rituximab induction in follicular lymphoma: results of the randomized controlled phase III trial SAKK 35/03. J Clin Oncol. 2016 Feb 10;34(5):495-500. Epub 2015 Dec 28. link to original article contains verified protocol link to PMC article PubMed
CT-P10 3.4: Ogura M, Sancho JM, Cho SG, Nakazawa H, Suzumiya J, Tumyan G, Kim JS, Lennard A, Mariz J, Ilyin N, Jurczak W, Lopez Martinez A, Samoilova O, Zhavrid E, Yañez Ruiz E, Trneny M, Popplewell L, Coiffier B, Buske C, Kim WS, Lee SJ, Lee SY, Bae YJ, Kwak LW. Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 in comparison with rituximab in patients with previously untreated low-tumour-burden follicular lymphoma: a randomised, double-blind, parallel-group, phase 3 trial. Lancet Haematol. 2018 Nov;5(11):e543-e553. link to original article contains protocol PubMed

Advanced disease, first-line therapy, non-randomized or retrospective data

Bendamustine & Ofatumumab

back to top

Regimen

Study	Evidence
Czuczman et al. 2015 (C18083-2048)	Phase II

The subtypes of indolent lymphoma that this regimen was used for are not specified in the abstract. Given that follicular lymphoma is the most common indolent lymphoma, the regimen is included here.

Chemotherapy

Bendamustine 90 mg/m² IV once per day on days 1 & 2
Ofatumumab (Arzerra) as follows:
- Cycle 1: 300 mg IV once on day 1, then 1000 mg IV once on day 8
- Cycle 2 onwards: 1000 mg IV once on day 1

28-day cycle for 6 cycles

References

C18083-2048: Czuczman MS, Kahanic S, Forero A, Davis G, Munteanu M, Van Den Neste E, Offner F, Bron D, Quick D, Fowler N. Results of a phase II study of bendamustine and ofatumumab in untreated indolent B cell non-Hodgkin's lymphoma. Ann Hematol. 2015 Apr;94(4):633-41. Epub 2015 Jan 30. link to original article contains protocol PubMed

FR

back to top

FR: Fludarabine & Rituximab

Regimen

Study	Evidence	Efficacy
Czuczman et al. 2005	Phase II	ORR: 90%

Chemotherapy

Fludarabine (Fludara) as follows:
- Weeks 2, 6, 10, 14, 18, 22: 25 mg/m² IV once per day on days 1 to 5
Rituximab (Rituxan) as follows:
- Weeks 1 & 26: 375 mg/m² IV once per day on days 1 & 4
- Weeks 6, 14, 22: 375 mg/m² IV once 72 hours before day 1

26-week course

References

Czuczman MS, Koryzna A, Mohr A, Stewart C, Donohue K, Blumenson L, Bernstein ZP, McCarthy P, Alam A, Hernandez-Ilizaliturri F, Skipper M, Brown K, Chanan-Khan A, Klippenstein D, Loud P, Rock MK, Benyunes M, Grillo-Lopez A, Bernstein SH. Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma. J Clin Oncol. 2005 Feb 1;23(4):694-704. link to original article contains verified protocol PubMed

Ibritumomab tiuxetan monotherapy

back to top

Variant #1

Study	Evidence
Scholz et al. 2013	Phase II
Ibatici et al. 2013	Phase II

Recruitment in Scholz et al. was limited to patients at least 50 years old due to radiation safety concerns; Ibatici et al. was open to all adult patients greater than 18 years old. Treatment regimen is identical.

Radioimmunotherapy

Rituximab (Rituxan) 250 mg/m² IV once per day on days 1 & either day 8 or 9, given first on day 8 or 9
Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 15 MBq/kg (maximum dose of 1200 MBq) IV once on day 8 or 9, given second

8- to 9-day course

Variant #2, fractionated

Study	Evidence
Illidge et al. 2013 (FIZZ)	Phase II

This regimen was for patients with less than or equal to 20% bone marrow involvement; others received induction rituximab, first. See paper for details.

Radioimmunotherapy

Rituximab (Rituxan) 250 mg/m² IV once per day on day 1 & either day 8 or 9, given first on day 8 or 9
Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 11.1 MBq/kg (maximum dose of 888 MBq) IV once on either day 8 or 9, given second

8- to 12-week cycle for 2 cycles

References

Scholz CW, Pinto A, Linkesch W, Lindén O, Viardot A, Keller U, Hess G, Lastoria S, Lerch K, Frigeri F, Arcamone M, Stroux A, Frericks B, Pott C, Pezzutto A. 90Yttrium-ibritumomab-tiuxetan as first-line treatment for follicular lymphoma: 30 months of follow-up data from an international multicenter phase II clinical trial. J Clin Oncol. 2013 Jan 20;31(3):308-13. Epub 2012 Dec 10. link to original article contains verified protocol PubMed
FIZZ: Illidge TM, Mayes S, Pettengell R, Bates AT, Bayne M, Radford JA, Ryder WD, Le Gouill S, Jardin F, Tipping J, Zivanovic M, Kraeber-Bodere F, Bardies M, Bodet-Milin C, Malek E, Huglo D, Morschhauser F. Fractionated 90Y-ibritumomab tiuxetan radioimmunotherapy as an initial therapy of follicular lymphoma: an international phase II study in patients requiring treatment according to GELF/BNLI criteria. J Clin Oncol. 2014 Jan 20;32(3):212-8. Epub 2013 Dec 2. link to original article contains verified protocol PubMed
Ibatici A, Pica GM, Nati S, Vitolo U, Botto B, Ciochetto C, Petrini M, Galimberti S, Ciabatti E, Orciuolo E, Zinzani PL, Cascavilla N, Guolo F, Fraternali Orcioni G, Carella AM. Safety and efficacy of (90) Yttrium-ibritumomab-tiuxetan for untreated follicular lymphoma patients: an Italian cooperative study. Br J Haematol. 2014 Mar;164(5):710-6. Epub 2013 Dec 17. link to original article contains verified protocol PubMed

O-CHOP

back to top

O-CHOP: Ofatumumab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone

Regimen

Study	Evidence
Czuczman et al. 2012 (409 Study)	Phase II

Note: both 500 mg and 1000 mg doses of ofatumumab were tested, but since there was no increase in toxicity in patients receiving the 1000 mg dose, the 1000 mg dose was chosen for future ofatumumab trials "to avoid underdosing patients"

Chemotherapy

Ofatumumab (Arzerra) as follows:
- Cycle 1: 300 mg IV once on day 1
- Cycles 2 to 6: 1000 mg IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 3
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 3
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 3
Prednisone (Sterapred) 100 mg PO once per day on days 3 to 7

Supportive medications

Acetaminophen (Tylenol) 1000 mg (no route specified) before each dose of Ofatumumab (Arzerra)
Cetirizine (Zyrtec) 10 mg (or equivalent) PO before each dose of Ofatumumab (Arzerra)
Prednisolone (Millipred) (or equivalent) 100 mg before dose 1 and 2 of Ofatumumab (Arzerra)

21-day cycle for 6 cycles

References

Czuczman MS, Hess G, Gadeberg OV, Pedersen LM, Goldstein N, Gupta I, Jewell RC, Lin TS, Lisby S, Strange C, Windfeld K, Viardot A; 409 Study Investigators. Chemoimmunotherapy with ofatumumab in combination with CHOP in previously untreated follicular lymphoma. Br J Haematol. 2012 May;157(4):438-45. Epub 2012 Mar 13. link to original article contains verified protocol PubMed

PCR

back to top

PCR: Pentostatin, Cyclophosphamide, Rituximab

Regimen

Study	Evidence
Samaniego et al. 2015 (MDACC 2004-0818)	Phase II

Chemotherapy

Pentostatin (Nipent) 4 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 600 mg/m² IV once on day 1
Rituximab (Rituxan) 375 mg/m² IV once on day 1

Supportive medications

Ondansetron (Zofran) 8 mg (route not specified) prior to chemo
Diphenhydramine (Benadryl) 25 mg (route not specified) prior to chemo
500 ml of 5% dextrose/one-half normal saline before and after each pentostatin dose
Filgrastim (Neupogen) at the discretion of the treating physician
Cycle 1: Allopurinol (Zyloprim) 300 mg PO once per day on days 1 to 15
Trimethoprim-Sulfamethoxazole (Bactrim DS) once per day three days per week during and for 1 month following therapy
Acyclovir (Zovirax) 400 mg PO twice per day during and for 1 month following therapy

21-day cycle for 6 cycles

References

MDACC 2004-0818: Samaniego F, Hagemeister F, Romaguera JE, Fanale MA, Pro B, McLaughlin P, Rodriguez MA, Neelapu SS, Fayad L, Younes A, Feng L, Berkova Z, Khashab T, Sehgal L, Vega-Vasquez F, Kwak LW. Pentostatin, cyclophosphamide and rituximab for previously untreated advanced stage, low-grade B-cell lymphomas. Br J Haematol. 2015 Jun;169(6):814-23. Epub 2015 Mar 31. link to original article contains verified protocol link to PMC article PubMed
1. Update: Khashab T, Hagemeister F, Romaguera JE, Fanale MA, Pro B, McLaughlin P, Rodriguez MA, Neelapu SS, Fayad L, Younes A, Feng L, Vega F, Kwak LW, Samaniego F. Long-term overall- and progression-free survival after pentostatin, cyclophosphamide and rituximab therapy for indolent non-Hodgkin lymphoma. Br J Haematol. 2019 May;185(4):670-678. Epub 2019 Feb 28. link to original article PubMed

R-CMD

back to top

R-CMD: Rituximab, Cladribine, Mitoxantrone, Dexamethasone

Regimen

Study	Evidence
Sakai et al. 2015	Phase II

Note: the dose of dexamethasone in the manuscript text as well as the accompanying table is listed as 8 mg/body. It is unclear to us what this means.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cladribine (Leustatin) 0.10 mg/kg IV once per day on days 1 to 3
Mitoxantrone (Novantrone) 8 mg/m² IV once on day 1
Dexamethasone (Decadron) 8 mg/body (route not specified) on days 1 to 3

21-day cycle for 4 cycles

Subsequent treatment

Rituximab consolidation

References

Sakai T, Masaki Y, Otsuki N, Sakamaki I, Kishi S, Miyazono T, Urasaki Y, Murakami J, Satoh T, Nakamura T, Iwao H, Nakajima A, Kawanami T, Miki M, Fujita Y, Tanaka M, Fukushima T, Okazaki T, Ueda T. Prospective clinical study of R-CMD therapy for indolent B cell lymphoma and mantle cell lymphoma from the Hokuriku Hematology Oncology Study Group. Med Oncol. 2015 Sep;32(9):232. contains verified protocol link to PMC article PubMed

R-FCM

back to top

R-FCM: Rituximab, Fludarabine, Cyclophosphamide, Mitoxantrone

Regimen

Study	Evidence
Salles et al. 2010 (PRIMA)	Non-randomized portion of RCT

Chemotherapy

Rituximab (Rituxan) as follows:
- Cycles 1, 3, 5, 6: 375 mg/m² IV once on day 1
- Cycles 2 & 4: 375 mg/m² IV once per day on days 1 & 15
Fludarabine (Fludara) 25 mg/m² IV once per day on days 1 to 3
Cyclophosphamide (Cytoxan) 200 mg/m² PO once per day on days 1 to 3
Mitoxantrone (Novantrone) 6 mg/m² IV once on day 1

28-day cycle for 6 cycles

Subsequent treatment

Responders (PR or CR): Rituximab maintenance versus no further treatment

References

PRIMA: Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. link to original article contains protocol PubMed
1. QoL Analysis: Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. link to original article PubMed
2. Update: Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. link to original article link to PMC article PubMed

VR

back to top

VR: Velcade (Bortezomib) & Rituximab

Regimen

Study	Evidence
Evens et al. 2014	Phase II

Chemotherapy

Bortezomib (Velcade) 1.6 mg/m² IV once per day on days 1, 8, 15, 22
Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22
- Cycles 2 & 3: 375 mg/m² IV once on day 1

35-day cycle for 3 cycles

Subsequent treatment

VR consolidation

References

Evens AM, Smith MR, Lossos IS, Helenowski I, Millenson M, Winter JN, Rosen ST, Gordon LI. Frontline bortezomib and rituximab for the treatment of newly diagnosed high tumour burden indolent non-hodgkin lymphoma: a multicentre phase II study. Br J Haematol. 2014 Aug;166(4):514-20. Epub 2014 Apr 25. link to original article contains verified protocol PubMed

VR-CHOP

back to top

VR-CHOP: Velcade (Bortezomib) Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne

Regimen

Study	Evidence
Cohen et al. 2015	Phase II

The largest group of patients studied in this trial had follicular lymphoma. Note the decreased cap on vincristine.

Chemotherapy

Bortezomib (Velcade) 1.6 mg/m² IV once per day on days 1 & 8
Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 1.5 mg) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for up to 8 cycles

Subsequent treatment

Patients with CR: Rituximab maintenance
Patients with SD/PR: VR maintenance

References

Cohen JB, Switchenko JM, Koff JL, Sinha R, Kaufman JL, Khoury HJ, Bumpers N, Colbert A, Hutchison-Rzepka A, Nastoupil LJ, Heffner LT, Langston AA, Lechowicz MJ, Lonial S, Flowers CR. A phase II study of bortezomib added to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients with previously untreated indolent non-Hodgkin's lymphoma. Br J Haematol. 2015 Nov;171(4):539-46. Epub 2015 Aug 7. link to original article contains protocol link to PMC article PubMed

Consolidation after first-line therapy

Note: consolidation here is defined as any regimen with an intended length of treatment of 12 months or less.

Ibritumomab tiuxetan monotherapy

back to top

An abstract presented at ASH 2013 from the ZAR2007 trial has preliminary results that R-CHOP followed by Zevalin is inferior to R-CHOP followed by rituximab maintenance; detailed results are not yet available and therefore only the reference is provided, here.

Variant #1

Study	Evidence	Comparator	Comparative Efficacy
Morschhauser et al. 2008 (FIT)	Phase III (E-RT-esc)	Observation	Superior PFS

Preceding treatment

First-line therapy (most received CHOP or CVP; some received "CHOP-like", "rituximab combination", "fludarabine combination", or chlorambucil), with PR/CR

Radioimmunotherapy

Rituximab (Rituxan) 250 mg/m² IV once per day on days 1 & 8
Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 14.8 MBq/kg (maximum dose of 1184 MBq) IV over 10 minutes once on day 8, immediately following Rituximab (Rituxan)

8-day course

Variant #2

Study	Evidence	Efficacy
Zinzani et al. 2011	Phase II	ORR: 89%

Preceding treatment

FMR

Radioimmunotherapy

Rituximab (Rituxan) 250 mg/m² IV once per day on days 1 & 8 +/- 1 day (total dose: 500 mg/m²)
Ibritumomab tiuxetan & Yttrium-90 (Zevalin) given immediately following second dose of rituximab, as follows:
- Platelet count greater than 150 x 10⁹/L: 14.8 MBq/kg (maximum dose of 1184 MBq) IV over 10 minutes once on day 8
- Platelet count of 100 to 149 x 10⁹/L: 11.1 MBq/kg (maximum dose of 1184 MBq) IV over 10 minutes once on day 8

8-day course

Variant #3

Study	Evidence
Hainsworth et al. 2009	Phase II

See text for further information about Zevalin eligbility criteria. If patient did not meet criteria within 7 weeks after final R-CHOP, Zevalin was omitted.

Preceding treatment

R-CHOP x 3

Radioimmunotherapy

Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg
- Dose reduced to 0.3 mCi/kg if platelet count 100 to 149 x 10⁹/L)

8-day course

Variant #4

Study	Evidence	Efficacy
Zinzani et al. 2008 (FLUMIZ)	Phase II	ORR: 98%

Preceding treatment

FM

Radioimmunotherapy

Rituximab (Rituxan) 250 mg/m² IV once per day on days 1 & 8 +/- 1 day (total dose: 500 mg/m²)
Ibritumomab tiuxetan & Yttrium-90 (Zevalin) given immediately following second dose of rituximab, as follows:
- Platelet count greater than 150 x 10⁹/L: 14.8 MBq/kg (maximum dose of 1184 MBq) IV over 10 minutes once on day 8
- Platelet count of 100 to 149 x 10⁹/L: 11.1 MBq/kg (maximum dose of 1184 MBq) IV over 10 minutes once on day 8

8-day course

Variant #5

Study	Evidence	Efficacy
Jacobs et al. 2008	Phase II	ORR: 89%

Preceding treatment

R-CHOP x 3

Radioimmunotherapy

Rituximab (Rituxan) 250 mg/m² IV once per day on days 1 & 8
Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (15 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV over 10 minutes once on day 8, given immediately following rituximab

8-day course, followed in 1 to 2 weeks by:

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days 1, 8, 15, 22

28-day course

Variant #6

Study	Evidence	Efficacy
Provencio et al. 2013	Phase II	ORR: 93%

To be completed; further details are not available in the abstract.

Preceding treatment

R-CHOP x 4, then CHOP x 2

Radioimmunotherapy

Ibritumomab tiuxetan (Zevalin)

References

FLUMIZ: Zinzani PL, Tani M, Pulsoni A, Gobbi M, Perotti A, De Luca S, Fabbri A, Zaccaria A, Voso MT, Fattori P, Guardigni L, Ronconi S, Cabras MG, Rigacci L, De Renzo A, Marchi E, Stefoni V, Fina M, Pellegrini C, Musuraca G, Derenzini E, Pileri S, Fanti S, Piccaluga PP, Baccarani M. Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase II non-randomised trial (FLUMIZ). Lancet Oncol. 2008 Apr;9(4):352-8. Epub 2008 Mar 14. link to original article contains verified protocol PubMed
FIT: Morschhauser F, Radford J, Van Hoof A, Vitolo U, Soubeyran P, Tilly H, Huijgens PC, Kolstad A, d'Amore F, Gonzalez Diaz M, Petrini M, Sebban C, Zinzani PL, van Oers MH, van Putten W, Bischof-Delaloye A, Rohatiner A, Salles G, Kuhlmann J, Hagenbeek A. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol. 2008 Nov 10;26(32):5156-64. Epub 2008 Oct 14. link to original article contains protocol PubMed
1. Update: Morschhauser F, Radford J, Van Hoof A, Botto B, Rohatiner AZ, Salles G, Soubeyran P, Tilly H, Bischof-Delaloye A, van Putten WL, Kylstra JW, Hagenbeek A. 90Yttrium-ibritumomab tiuxetan consolidation of first remission in advanced-stage follicular non-Hodgkin lymphoma: updated results after a median follow-up of 7.3 years from the international, randomized, phase III First-Line Indolent Trial. J Clin Oncol. 2013 Jun 1;31(16):1977-83. Epub 2013 Apr 1. link to original article contains protocol PubMed
Jacobs SA, Swerdlow SH, Kant J, Foon KA, Jankowitz R, Land SR, DeMonaco N, Joyce J, Osborn JL, Evans TL, Schaefer PM, Luong TM. Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Clin Cancer Res. 2008 Nov 1;14(21):7088-94. link to original article contains verified protocol PubMed
Hainsworth JD, Spigel DR, Markus TM, Shipley D, Thompson D, Rotman R, Dannaher C, Greco FA. Rituximab plus short-duration chemotherapy followed by yttrium-90 ibritumomab tiuxetan as first-line treatment for patients with follicular non-Hodgkin lymphoma: a phase II trial of the Sarah Cannon Oncology Research Consortium. Clin Lymphoma Myeloma. 2009 Jun;9(3):223-8. link to SD article contains verified protocol PubMed
Zinzani PL, Tani M, Pulsoni A, De Renzo A, Stefoni V, Broccoli A, Montini GC, Fina M, Pellegrini C, Gandolfi L, Cavalieri E, Torelli F, Scopinaro F, Argnani L, Quirini F, Derenzini E, Rossi M, Pileri S, Fanti S, Baccarani M. A phase II trial of short course fludarabine, mitoxantrone, rituximab followed by ⁹⁰Y-ibritumomab tiuxetan in untreated intermediate/high-risk follicular lymphoma. Ann Oncol. 2012 Feb;23(2):415-20. Epub 2011 May 2. link to original article contains verified protocol PubMed
Provencio M, Cruz Mora MÁ, Gómez-Codina J, Quero Blanco C, Llanos M, García-Arroyo FR, de la Cruz L, Gumá Padró J, Delgado Pérez JR, Sánchez A, Alvarez Cabellos R, Rueda A; Gotel (Spanish Lymphoma Oncology Group). Consolidation treatment with Yttrium-90 ibritumomab tiuxetan after new induction regimen in patients with intermediate- and high-risk follicular lymphoma according to the follicular lymphoma international prognostic index: a multicenter, prospective phase II trial of the Spanish Lymphoma Oncology Group. Leuk Lymphoma. 2014 Jan;55(1):51-5. Epub 2013 Jun 12. link to original article PubMed
Abstract: Armando Lopez-Guillermo, MD, PhD, Miguel A. Canales, MD, PhD, Ivan Dlouhy, Javier Briones, MD, Dolores Caballero, MD, PhD, Juan Manuel Sancho Sr., MD, Santiago Mercadal Vilchez, MD, Jose María Moraleda, MD, María José Terol, MD, PhD, Antonio Salar, MD, Luis Palomera, MD, Santiago Gardella, MD, Isidro Jarque, MD, Secundino Ferrer, Joan Bargay, MD, Andres Lopez, Carlos Panizo, Anna Muntanola, MD, Carlos Montalban, Eulogio Conde, MD, PhD, Miguel Hernandez, MD, Alfons Soler, Julian Marin, MD, Jose García Marco, Guillermo Deben and José Francisco Tomas, MD, PhD. A Randomized Phase II Study Comparing Consolidation With a Single Dose Of 90y Ibritumomab Tiuxetan (Zevalin®) (Z) Vs. Maintenance With Rituximab (R) For Two Years In Patients With Newly Diagnosed Follicular Lymphoma (FL) Responding To R-CHOP. Preliminary Results At 36 Months From Randomization. Blood 2013 122:369. link to abstract

Observation

back to top

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Hagenbeek et al. 1998	Phase III (C)	Interferon alfa	Might have inferior TTP
Fisher et al. 2000 (SWOG S8809)	Phase III (C)	Interferon alfa	Did not meet primary endpoints of PFS/OS
Ghielmini et al. 2004 (SAKK 35/98)	Phase III (C)	Rituximab	Seems to have inferior EFS
Morschhauser et al. 2008 (FIT)	Phase III (C)	Ibritumomab tiuxetan	Inferior PFS
Hochster et al. 2009 (ECOG E1496)	Phase III (C)	Rituximab	Inferior PFS
Salles et al. 2010 (PRIMA)	Phase III (C)	Rituximab	Inferior PFS
Vitolo et al. 2013 (ML17638)	Phase III (C)	Rituximab	Did not meet primary endpoint of PFS

No further treatment after induction therapy.

Preceding treatment

SAKK 35/98: R x 4
FIT: First-line therapy (most received CHOP or CVP; some received "CHOP-like", "rituximab combination", "fludarabine combination", or chlorambucil), with PR/CR
ECOG E1496: CVP x 6 to 8
PRIMA: R-CHOP or R-CVP or R-FCM
ML17638: R-FND x 4

References

Hagenbeek A, Carde P, Meerwaldt JH, Somers R, Thomas J, De Bock R, Raemaekers JM, van Hoof A, De Wolf-Peeters C, van Glabbeke M; European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group. Maintenance of remission with human recombinant interferon alfa-2a in patients with stages III and IV low-grade malignant non-Hodgkin's lymphoma. J Clin Oncol. 1998 Jan;16(1):41-7. link to original article PubMed
SWOG S8809: Fisher RI, Dana BW, LeBlanc M, Kjeldsberg C, Forman JD, Unger JM, Balcerzak SP, Gaynor ER, Roy V, Miller T. Interferon alpha consolidation after intensive chemotherapy does not prolong the progression-free survival of patients with low-grade non-Hodgkin's lymphoma: results of the Southwest Oncology Group randomized phase III study 8809. J Clin Oncol. 2000 May;18(10):2010-6. link to original article PubMed
SAKK 35/98: Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. link to original article contains protocol PubMed
1. Update: Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. link to original article contains verified protocol PubMed
FIT: Morschhauser F, Radford J, Van Hoof A, Vitolo U, Soubeyran P, Tilly H, Huijgens PC, Kolstad A, d'Amore F, Gonzalez Diaz M, Petrini M, Sebban C, Zinzani PL, van Oers MH, van Putten W, Bischof-Delaloye A, Rohatiner A, Salles G, Kuhlmann J, Hagenbeek A. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol. 2008 Nov 10;26(32):5156-64. Epub 2008 Oct 14. link to original article contains protocol PubMed
1. Update: Morschhauser F, Radford J, Van Hoof A, Botto B, Rohatiner AZ, Salles G, Soubeyran P, Tilly H, Bischof-Delaloye A, van Putten WL, Kylstra JW, Hagenbeek A. 90Yttrium-ibritumomab tiuxetan consolidation of first remission in advanced-stage follicular non-Hodgkin lymphoma: updated results after a median follow-up of 7.3 years from the international, randomized, phase III First-Line Indolent Trial. J Clin Oncol. 2013 Jun 1;31(16):1977-83. Epub 2013 Apr 1. link to original article contains protocol PubMed
ECOG E1496: Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. Epub 2009 Mar 2. link to original article contains verified protocol link to PMC article PubMed
1. Update: Barta SK, Li H, Hochster HS, Hong F, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Colocci N, Bengtson EM, Horning SJ, Kahl BS. Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496). Cancer. 2016 Oct;122(19):2996-3004. Epub 2016 Jun 28. link to original article link to PMC article PubMed
PRIMA: Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. link to original article contains protocol PubMed
1. QoL Analysis: Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. link to original article PubMed
2. Update: Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. link to original article link to PMC article PubMed
ML17638: Vitolo U, Ladetto M, Boccomini C, Baldini L, De Angelis F, Tucci A, Botto B, Chiappella A, Chiarenza A, Pinto A, De Renzo A, Zaja F, Castellino C, Bari A, Alvarez De Celis I, Evangelista A, Parvis G, Gamba E, Lobetti-Bodoni C, Ciccone G, Rossi G. Rituximab maintenance compared with observation after brief first-line R-FND chemoimmunotherapy with rituximab consolidation in patients age older than 60 years with advanced follicular lymphoma: a phase III randomized study by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Sep 20;31(27):3351-9. Epub 2013 Aug 19. link to original article contains verified protocol PubMed

Rituximab monotherapy, abbreviated course

back to top

Consolidation or maintenance regimens of less than one year duration or less than 12 total doses.

Variant #1, 2 doses in 2 weeks

Study	Evidence
Hainsworth et al. 2005a	Phase II

Counting from the beginning, this is given in weeks 14 & 15.

Preceding treatment

Rituximab pre-phase x 4, then R-CHOP x 3

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days 1 & 8

14-day course

Variant #2, 4 doses in 4 weeks

Study	Evidence
Rambaldi et al. 2002	Phase II
Hainsworth et al. 2002	Phase II
Ladetto et al. 2008	Non-randomized portion of RCT

Preceding treatment

Rambaldi et al. 2002 & Ladetto et al. 2008: CHOP x 6
Hainsworth et al. 2002: Rituximab
Zinzani et al. 2004: CHOP x 6 versus FM x 6

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days 1, 8, 15, 22

Supportive medications

Acetaminophen (Tylenol) 650 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to Rituximab (Rituxan)
Diphenhydramine (Benadryl) 50 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to Rituximab (Rituxan)

4-week course

Variant #3, 4 doses in 4 months

Study	Evidence
Sakai et al. 2015	Phase II

Preceding treatment

R-CMD x 4

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

28-day cycle for 4 cycles

Variant #4, 8 doses in 8 months

Study	Evidence	Comparator	Comparative Efficacy
Vitolo et al. 2013 (ML17638)	Phase III (E-esc)	Observation	Did not meet primary endpoint of PFS

Preceding treatment

R-FND

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

2-month cycle for 4 cycles

Variant #5, 8 doses in 9 months

Study	Evidence	Comparator	Comparative Efficacy
Ghielmini et al. 2004 (SAKK 35/98)	Phase III (E-esc)	Observation	Seems to have superior EFS
Taverna et al. 2015 (SAKK 35/03)	Phase III (C)	Rituximab x 5 y	Did not meet primary endpoint of EFS

Note: maintenance treatment begins in week 12.

Preceding treatment

Rituximab

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

2-month cycle for 4 cycles

References

Rambaldi A, Lazzari M, Manzoni C, Carlotti E, Arcaini L, Baccarani M, Barbui T, Bernasconi C, Dastoli G, Fuga G, Gamba E, Gargantini L, Gattei V, Lauria F, Lazzarino M, Mandelli F, Morra E, Pulsoni A, Ribersani M, Rossi-Ferrini PL, Rupolo M, Tura S, Zagonel V, Zaja F, Zinzani P, Reato G, Foa R. Monitoring of minimal residual disease after CHOP and rituximab in previously untreated patients with follicular lymphoma. Blood. 2002 Feb 1;99(3):856-62. link to original article contains verified protocol PubMed
Hainsworth JD, Litchy S, Burris HA 3rd, Scullin DC Jr, Corso SW, Yardley DA, Morrissey L, Greco FA. Rituximab as first-line and maintenance therapy for patients with indolent non-hodgkin's lymphoma. J Clin Oncol. 2002 Oct 15;20(20):4261-7. link to original article contains protocol PubMed
SAKK 35/98: Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. link to original article contains protocol PubMed
1. Update: Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. link to original article contains verified protocol PubMed
Hainsworth JD, Litchy S, Morrissey LH, Andrews MB, Grimaldi M, McCarty M, Greco FA. Rituximab plus short-duration chemotherapy as first-line treatment for follicular non-Hodgkin's lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Mar 1;23(7):1500-6. Epub 2005 Jan 4. link to original article contains verified protocol PubMed
Ladetto M, De Marco F, Benedetti F, Vitolo U, Patti C, Rambaldi A, Pulsoni A, Musso M, Liberati AM, Olivieri A, Gallamini A, Pogliani E, Rota Scalabrini D, Callea V, Di Raimondo F, Pavone V, Tucci A, Cortelazzo S, Levis A, Boccadoro M, Majolino I, Pileri A, Gianni AM, Passera R, Corradini P, Tarella C; Gruppo Italiano Trapianto di Midollo Osseo (GITMO); Intergruppo Italiano Linfomi (IIL). Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage. Blood. 2008 Apr 15;111(8):4004-13. Epub 2008 Jan 31. link to original article contains protocol PubMed
ML17638: Vitolo U, Ladetto M, Boccomini C, Baldini L, De Angelis F, Tucci A, Botto B, Chiappella A, Chiarenza A, Pinto A, De Renzo A, Zaja F, Castellino C, Bari A, Alvarez De Celis I, Evangelista A, Parvis G, Gamba E, Lobetti-Bodoni C, Ciccone G, Rossi G. Rituximab maintenance compared with observation after brief first-line R-FND chemoimmunotherapy with rituximab consolidation in patients age older than 60 years with advanced follicular lymphoma: a phase III randomized study by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Sep 20;31(27):3351-9. Epub 2013 Aug 19. link to original article contains verified protocol PubMed
Sakai T, Masaki Y, Otsuki N, Sakamaki I, Kishi S, Miyazono T, Urasaki Y, Murakami J, Satoh T, Nakamura T, Iwao H, Nakajima A, Kawanami T, Miki M, Fujita Y, Tanaka M, Fukushima T, Okazaki T, Ueda T. Prospective clinical study of R-CMD therapy for indolent B cell lymphoma and mantle cell lymphoma from the Hokuriku Hematology Oncology Study Group. Med Oncol. 2015 Sep;32(9):232. contains verified protocol link to PMC article PubMed
SAKK 35/03: Taverna C, Martinelli G, Hitz F, Mingrone W, Pabst T, Cevreska L, Del Giglio A, Vanazzi A, Laszlo D, Raats J, Rauch D, Vorobiof DA, Lohri A, Biaggi Rudolf C, Rondeau S, Rusterholz C, Heijnen IA, Zucca E, Ghielmini M. Rituximab maintenance for a maximum of 5 years after single-agent rituximab induction in follicular lymphoma: results of the randomized controlled phase III trial SAKK 35/03. J Clin Oncol. 2016 Feb 10;34(5):495-500. Epub 2015 Dec 28. link to original article contains verified protocol link to PMC article PubMed

VR

back to top

VR: Velcade (Bortezomib) & Rituximab

Regimen

Study	Evidence
Evens et al. 2014	Phase II

Preceding treatment

VR induction

Chemotherapy

Bortezomib (Velcade) 1.6 mg/m² IV once on day 1
Rituximab (Rituxan) 375 mg/m² IV once on day 1

2-month cycle for 4 cycles

References

Evens AM, Smith MR, Lossos IS, Helenowski I, Millenson M, Winter JN, Rosen ST, Gordon LI. Frontline bortezomib and rituximab for the treatment of newly diagnosed high tumour burden indolent non-hodgkin lymphoma: a multicentre phase II study. Br J Haematol. 2014 Aug;166(4):514-20. Epub 2014 Apr 25. link to original article contains verified protocol PubMed

Maintenance after first-line therapy

Lenalidomide & Rituximab

back to top

R²: Rituximab & Revlimid (Lenalidomide)

Regimen

Study	Evidence
Morschhauser et al. 2018 (RELEVANCE)	Non-randomized portion of RCT

Preceding treatment

Lenalidomide & Rituximab induction

Chemotherapy

Lenalidomide (Revlimid) 10 mg PO once per day
Rituximab (Rituxan) 375 mg/m² IV once on day 1

8-week cycle for 12 cycles

References

RELEVANCE: Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. link to original article contains verified protocol PubMed

Obinutuzumab monotherapy

back to top

Regimen

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Marcus et al. 2017 (GALLIUM)	Phase III (E-RT-switch-ic)	See link	See link	style="background-color:#d73027" \|See link

Preceding treatment

G-B x 6 or G-CHOP x 6 or G-CVP x 6

Chemotherapy

Obinutuzumab (Gazyva) 1000 mg IV once on day 1

2-month cycle for 12 cycles

References

GALLIUM: Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. link to original article link to appendix contains verified protocol in appendix PubMed
1. Update: Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. link to original article PubMed

Placebo

back to top

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Freedman et al. 2009	Phase III (C)	Mitumprotimut-T & GM-CSF	Seems to have superior TTP

No active antineoplastic treatment.

Preceding treatment

Rituximab x 4

References

Freedman A, Neelapu SS, Nichols C, Robertson MJ, Djulbegovic B, Winter JN, Bender JF, Gold DP, Ghalie RG, Stewart ME, Esquibel V, Hamlin P. Placebo-controlled phase III trial of patient-specific immunotherapy with mitumprotimut-T and granulocyte-macrophage colony-stimulating factor after rituximab in patients with follicular lymphoma. J Clin Oncol. 2009 Jun 20;27(18):3036-43. Epub 2009 May 4. link to original article link to PMC article PubMed

Rituximab monotherapy, extended course

back to top

Maintenance regimens of one to two years duration or 12 to 16 total doses.

Variant #1, q8wk cycles

Study	Evidence	Comparator	Comparative Efficacy
Salles et al. 2010 (PRIMA)	Phase III (E-RT-esc)	Observation	Superior PFS
Davies et al. 2017 (SABRINA)	Phase III (C)	SC Rituximab	Similar efficacy

Starts 8 weeks after the last induction treatment.

Preceding treatment

PRIMA: R-CHOP or R-CVP or R-FCM
SABRINA: R-CHOP or R-CVP

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

8-week cycle for 12 cycles

Variant #2, q6mo cycles

Study	Evidence	Comparator	Comparative Efficacy
Hochster et al. 2009 (ECOG E1496)	Phase III (E-RT-esc)	Observation	Superior PFS

Preceding treatment

CVP x 6 to 8 cycles

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days 1, 8, 15, 22

6-month cycle for 4 cycles (2 years)

Variant #3

Study	Evidence	Comparator	Comparative Efficacy
Ardeshna et al. 2014 (CRUK-2004-001621-16)	Phase III (E-esc)	1. Observation	Superior TTNT
Ardeshna et al. 2014 (CRUK-2004-001621-16)	Phase III (E-esc)	2. Rituximab induction, no maintenance	Did not meet primary endpoint of TTNT

Preceding treatment

Rituximab induction

Chemotherapy

Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22
- Cycles 2 to 13: 375 mg/m² IV once on day 1

28-day cycle for 1 cycle, then 2-month cycle for 12 cycles

Variant #4

Study	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Rummel et al. 2014 (MAINTAIN)	Phase III (C)	Rituximab x 4y	TBD
Witzens-Harig et al. 2014 (MAXIMA)	Non-randomized
Marcus et al. 2017 (GALLIUM)	Phase III (C)	See link	See link	See link

Preceding treatment

MAINTAIN: BR x 6 and 2 doses of rituximab
MAXIMA: Rituximab monotherapy or rituximab and chemotherapy (Most patients, 62%, received an anthracycline-based regimen)
GALLIUM: BR x 6 or R-CHOP x 8 or R-CVP x 8

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

2-month cycle for 12 cycles (2 years)

References

Meta-analysis: Vidal L, Gafter-Gvili A, Leibovici L, Dreyling M, Ghielmini M, Hsu Schmitz SF, Cohen A, Shpilberg O. Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials. J Natl Cancer Inst. 2009 Feb 18;101(4):248-55. Epub 2009 Feb 10. PubMed
ECOG E1496: Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. Epub 2009 Mar 2. link to original article contains verified protocol link to PMC article PubMed
1. Update: Barta SK, Li H, Hochster HS, Hong F, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Colocci N, Bengtson EM, Horning SJ, Kahl BS. Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496). Cancer. 2016 Oct;122(19):2996-3004. Epub 2016 Jun 28. link to original article link to PMC article PubMed
PRIMA: Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. link to original article contains protocol PubMed
1. QoL Analysis: Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. link to original article PubMed
2. Update: Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. link to original article link to PMC article PubMed
CRUK-2004-001621-16: Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P, Warden J, Stevens L, Pocock CF, Miall F, Cunningham D, Davies J, Jack A, Stephens R, Walewski J, Ferhanoglu B, Bradstock K, Linch DC. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol. 2014 Apr;15(4):424-35. Epub 2014 Mar 4. link to original article contains verified protocol PubMed
MAXIMA: Witzens-Harig M, Foá R, Di Rocco A, van Hazel G, Chamone DF, Rowe JM, Arcaini L, Poddubnaya I, Ho AD, Ivanova V, Vranovsky A, Thurley D, Oertel S. Maintenance with rituximab is safe and not associated with severe or uncommon infections in patients with follicular lymphoma: results from the phase IIIb MAXIMA study. Ann Hematol. 2014 Oct;93(10):1717-24. Epub 2014 May 14. Erratum in: Ann Hematol. 2014 Oct;93(10):1807. link to original article contains verified protocol PubMed
Abstract: Mathias J. Rummel, MD, Andreas Viardot, Richard Greil, MD, Bernd Hertenstein, MD, Christian Lerchenmüller, MD, Arnold Ganser, Manfred Reeb, MD, Ulrich Kaiser, MD, Christina Balser, MD, Georg Maschmeyer, MD, Heinz Dürk, MD, Georg Schliesser, MD, Tobias Gaska, MD, Jan Dürig, MD, Axel C. Matzdorff, MD, Rudolf Weide, MD, Axel Hinke, PhD, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Jürgen Barth and Wolfram Brugger, MD. Bendamustine Plus Rituximab Followed By Rituximab Maintenance for Patients with Untreated Advanced Follicular Lymphomas. Results from the StiL NHL 7-2008 Trial (MAINTAIN trial) (ClinicalTrials.gov Identifier: NCT00877214). Blood 2014 124:3052. link to abstract
SABRINA: Davies A, Merli F, Mihaljević B, Mercadal S, Siritanaratkul N, Solal-Céligny P, Boehnke A, Berge C, Genevray M, Zharkov A, Dixon M, Brewster M, Barrett M, MacDonald D. Efficacy and safety of subcutaneous rituximab versus intravenous rituximab for first-line treatment of follicular lymphoma (SABRINA): a randomised, open-label, phase 3 trial. Lancet Haematol. 2017 Jun;4(6):e272-e282. Epub 2017 May 2. link to original article does not contain protocol PubMed
GALLIUM: Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. link to original article link to appendix contains verified protocol in appendix PubMed
1. Update: Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. link to original article PubMed

Rituximab monotherapy, very extended course

back to top

Maintenance regimens of more than two years duration.

Variant #1, 4 years

Study	Evidence	Comparator	Comparative Efficacy
Rummel et al. 2014 (MAINTAIN)	Phase III (E-esc)	Rituximab x 2 y	TBD

Preceding treatment

BR x 6 and 2 doses of rituximab

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

2-month cycle for 24 cycles (4 years)

Variant #2, 5 years

Study	Evidence	Comparator	Comparative Efficacy
Taverna et al. 2015 (SAKK 35/03)	Phase III (E-esc)	Rituximab x 9 mo	Did not meet primary endpoint of EFS

Preceding treatment

Rituximab

Chemotherapy

Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22
- Cycles 2 to 30: 375 mg/m² IV once on day 1

2-month cycle for up to 30 cycles (5 years)

Variant #3, indefinite

Study	Evidence	Comparator	Comparative Efficacy
Kahl et al. 2014 (RESORT)	Phase III (E-esc)	Rituximab; salvage	Did not meet primary endpoint of TTF

Preceding treatment

Rituximab

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

13-week cycles

References

Abstract: Mathias J. Rummel, MD, Andreas Viardot, Richard Greil, MD, Bernd Hertenstein, MD, Christian Lerchenmüller, MD, Arnold Ganser, Manfred Reeb, MD, Ulrich Kaiser, MD, Christina Balser, MD, Georg Maschmeyer, MD, Heinz Dürk, MD, Georg Schliesser, MD, Tobias Gaska, MD, Jan Dürig, MD, Axel C. Matzdorff, MD, Rudolf Weide, MD, Axel Hinke, PhD, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Jürgen Barth and Wolfram Brugger, MD. Bendamustine Plus Rituximab Followed By Rituximab Maintenance for Patients with Untreated Advanced Follicular Lymphomas. Results from the StiL NHL 7-2008 Trial (MAINTAIN trial) (ClinicalTrials.gov Identifier: NCT00877214). Blood 2014 124:3052. link to abstract
ECOG E4402: Kahl BS, Hong F, Williams ME, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ. Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: Eastern Cooperative Oncology Group protocol E4402. J Clin Oncol. 2014 Oct 1;32(28):3096-102. Epub 2014 Aug 25. link to original article contains verified protocol link to PMC article PubMed
SAKK 35/03: Taverna C, Martinelli G, Hitz F, Mingrone W, Pabst T, Cevreska L, Del Giglio A, Vanazzi A, Laszlo D, Raats J, Rauch D, Vorobiof DA, Lohri A, Biaggi Rudolf C, Rondeau S, Rusterholz C, Heijnen IA, Zucca E, Ghielmini M. Rituximab maintenance for a maximum of 5 years after single-agent rituximab induction in follicular lymphoma: results of the randomized controlled phase III trial SAKK 35/03. J Clin Oncol. 2016 Feb 10;34(5):495-500. Epub 2015 Dec 28. link to original article contains verified protocol link to PMC article PubMed

Rituximab and hyaluronidase monotherapy

back to top

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Davies et al. 2017 (SABRINA)	Phase III (E-RT-switch-ic)	IV Rituximab	Similar efficacy

Starts 8 weeks after the last induction treatment.

Preceding treatment

R-CHOP or R-CVP

Chemotherapy

Rituximab and hyaluronidase human (Rituxan Hycela) 1400 mg SC once on day 1

8-week cycle for 12 cycles

References

SABRINA: Davies A, Merli F, Mihaljević B, Mercadal S, Siritanaratkul N, Solal-Céligny P, Boehnke A, Berge C, Genevray M, Zharkov A, Dixon M, Brewster M, Barrett M, MacDonald D. Efficacy and safety of subcutaneous rituximab versus intravenous rituximab for first-line treatment of follicular lymphoma (SABRINA): a randomised, open-label, phase 3 trial. Lancet Haematol. 2017 Jun;4(6):e272-e282. Epub 2017 May 2. link to original article does not contain protocol PubMed

VR

back to top

VR: Velcade (Bortezomib) & Rituximab

Regimen

Study	Evidence
Cohen et al. 2015	Phase II

Preceding treatment

VR-CHOP x 6 to 8

Chemotherapy

Bortezomib (Velcade) 1.6 mg/m² IV once per day on days 1, 8, 15, 22
Rituximab (Rituxan) 375 mg/m² IV once per day on days 1, 8, 15, 22

6-month cycle for up to 4 cycles (2 years)

References

Cohen JB, Switchenko JM, Koff JL, Sinha R, Kaufman JL, Khoury HJ, Bumpers N, Colbert A, Hutchison-Rzepka A, Nastoupil LJ, Heffner LT, Langston AA, Lechowicz MJ, Lonial S, Flowers CR. A phase II study of bortezomib added to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients with previously untreated indolent non-Hodgkin's lymphoma. Br J Haematol. 2015 Nov;171(4):539-46. Epub 2015 Aug 7. link to original article link to PMC article contains verified protocol PubMed

Relapsed or refractory, randomized data

Bendamustine monotherapy

back to top

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Friedberg et al. 2008	Phase II
Kahl et al. 2010	Phase II (RT)
Sehn et al. 2016 (GADOLIN)	Phase III (C)	Bendamustine & Obinutuzumab	Seems to have inferior OS (*)

Note: efficacy in GADOLIN is based on the 2018 update.

Chemotherapy

Bendamustine 120 mg/m² IV once per day on days 1 & 2

21- to 28-day cycle for 6 to 8 cycles (up to 12 in Friedberg et al. 2008)

References

Friedberg JW, Cohen P, Chen L, Robinson KS, Forero-Torres A, La Casce AS, Fayad LE, Bessudo A, Camacho ES, Williams ME, van der Jagt RH, Oliver JW, Cheson BD. Bendamustine in patients with rituximab-refractory indolent and transformed non-Hodgkin's lymphoma: results from a phase II multicenter, single-agent study. J Clin Oncol. 2008 Jan 10;26(2):204-10. Erratum in: J Clin Oncol. 2008 Apr 10;26(11) 1911. link to original article contains verified protocol PubMed
Kahl BS, Bartlett NL, Leonard JP, Chen L, Ganjoo K, Williams ME, Czuczman MS, Robinson KS, Joyce R, van der Jagt RH, Cheson BD. Bendamustine is effective therapy in patients with rituximab-refractory, indolent B-cell non-Hodgkin lymphoma: results from a multicenter study. Cancer. 2010 Jan 1;116(1):106-14. link to original article contains verified protocol link to PMC article PubMed
GADOLIN: Sehn LH, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben J, Lennard A, Lugtenburg PJ, Dimier N, Wassner-Fritsch E, Fingerle-Rowson G, Cheson BD. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1081-93. Epub 2016 Jun 23. link to original article contains protocol PubMed
1. Update: Cheson BD, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben JG, Lennard A, Lugtenburg PJ, Fingerle-Rowson G, Mattiello F, Knapp A, Sehn LH. Overall survival benefit in patients with rituximab-refractory indolent non-Hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study. J Clin Oncol. 2018 Aug 1;36(22):2259-2266. Epub 2018 Mar 27. link to original article PubMed

Bendamustine & Obinutuzumab

back to top

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Sehn et al. 2016 (GADOLIN)	Phase III (E-RT-esc)	Bendamustine	Seems to have superior OS

Note: efficacy is based on the 2018 update.

Chemotherapy

Bendamustine 90 mg/m² IV once per day on days 1 & 2
Obinutuzumab (Gazyva) as follows:
- Cycle 1: 1000 mg IV once per day on days 1, 8, 15
- Cycles 2 to 6: 1000 mg IV once on day 1

28-day cycle for 6 cycles

Subsequent treatment

Obinutuzumab maintenance

References

GADOLIN: Sehn LH, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben J, Lennard A, Lugtenburg PJ, Dimier N, Wassner-Fritsch E, Fingerle-Rowson G, Cheson BD. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1081-93. Epub 2016 Jun 23. link to original article contains protocol PubMed
1. Update: Cheson BD, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben JG, Lennard A, Lugtenburg PJ, Fingerle-Rowson G, Mattiello F, Knapp A, Sehn LH. Overall survival benefit in patients with rituximab-refractory indolent non-Hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study. J Clin Oncol. 2018 Aug 1;36(22):2259-2266. Epub 2018 Mar 27. link to original article PubMed

Bevacizumab & Rituximab

back to top

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Hainsworth et al. 2014	Randomized (E-esc)	Rituximab	Seems to have superior PFS

Chemotherapy

Bevacizumab (Avastin) as follows:
- Cycle 1: 10 mg/kg IV once per day on days 3 & 15
- Cycles 2 to 5: 10 mg/kg IV once per day on days 1, 15, 29, 43
Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22
- Cycles 2 to 5: 375 mg/m² IV once on day 1

12-week cycle for 1 cycle, then 2-month cycle for 4 cycles

References

Hainsworth JD, Greco FA, Raefsky EL, Thompson DS, Lunin S, Reeves J Jr, White L, Quinn R, DeBusk LM, Flinn IW. Rituximab with or without bevacizumab for the treatment of patients with relapsed follicular lymphoma. Clin Lymphoma Myeloma Leuk. 2014 Aug;14(4):277-83. Epub 2014 Feb 28. link to original article contains verified protocol PubMed

BR

back to top

BR: Bendamustine, Rituximab

Variant #1, 4 cycles

Study	Evidence
Matsumoto et al. 2015 (BRB)	Phase II

Note: rituximab could be given on day 0, 1, 2, or 3 "according to the clinical convenience of each institution."

Chemotherapy

Bendamustine 90 mg/m² IV once per day on days 1 & 2
Rituximab (Rituxan) 375 mg/m² IV once on day 1

28-day cycle for 4 cycles

Variant #2, 4 cycles with rituximab lead-in

Study	Evidence
Rummel et al. 2005	Phase II
Robinson et al. 2008	Phase II

Note: Robinson et al. 2008 said that patients "could receive up to six cycles if disease regression was evident between the second and fourth cycles".

Chemotherapy

Rituximab (Rituxan) as follows:
- One week prior to start of cycle 1: 375 mg/m² IV once
- Cycles 1 to 4: 375 mg/m² IV once on day 1
- 4 weeks after cycle 4: 375 mg/m² IV once
Bendamustine 90 mg/m² IV once per day on days 2 & 3

28-day cycle for 4 cycles (see note)

Variant #3, 6 cycles

Study	Evidence	Comparator	Comparative Efficacy
Rummel et al. 2015 (StiL NHL 2-2003)	Phase III (E-switch-ic)	FR	Superior PFS

Chemotherapy

Bendamustine 90 mg/m² IV once per day on days 1 & 2
Rituximab (Rituxan) 375 mg/m² IV once on day 1

28-day cycle for up to 6 cycles

References

Rummel MJ, Al-Batran SE, Kim SZ, Welslau M, Hecker R, Kofahl-Krause D, Josten KM, Dürk H, Rost A, Neise M, von Grünhagen U, Chow KU, Hansmann ML, Hoelzer D, Mitrou PS. Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin's lymphoma. J Clin Oncol. 2005 May 20;23(15):3383-9. link to original article contains verified protocol PubMed
Robinson KS, Williams ME, van der Jagt RH, Cohen P, Herst JA, Tulpule A, Schwartzberg LS, Lemieux B, Cheson BD. Phase II multicenter study of bendamustine plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin's lymphoma. J Clin Oncol. 2008 Sep 20;26(27):4473-9. Epub 2008 Jul 14. link to original article contains verified protocol PubMed
BRB: Matsumoto K, Takayama N, Aisa Y, Ueno H, Hagihara M, Watanabe K, Nakaya A, Chen K, Shimizu T, Tsukada Y, Yamada Y, Nakazato T, Ishida A, Miyakawa Y, Yokoyama K, Nakajima H, Masuda Y, Yano T, Okamoto S; Keio BRB Study Group. A phase II study of bendamustine plus rituximab in Japanese patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma previously treated with rituximab: BRB study. Int J Hematol. 2015 Jun;101(6):554-62. Epub 2015 Mar 19. link to original article contains verified protocol PubMed
StiL NHL 2-2003: Rummel M, Kaiser U, Balser C, Stauch M, Brugger W, Welslau M, Niederle N, Losem C, Boeck HP, Weidmann E, von Gruenhagen U, Mueller L, Sandherr M, Hahn L, Vereshchagina J, Kauff F, Blau W, Hinke A, Barth J; Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial. Lancet Oncol. 2016 Jan;17(1):57-66. Epub 2015 Dec 5. link to original article contains protocol PubMed

Ibritumomab tiuxetan monotherapy

back to top

Variant #1, 0.3 mCi/kg

Study	Evidence
Wiseman et al. 2002	Phase II (RT)

Note: this dosing was intended for patients with mild thrombocytopenia.

Radioimmunotherapy

Rituximab (Rituxan) 250 mg/m² IV once per day on days 1 & 8
Ibritumomab tiuxetan 1.6 mg & Indium-111 5 mCi IV over 10 minutes once on day 1
Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.3 mCi/kg (11 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV over 10 minutes once on day 8, given immediately following rituximab

8-day course

Variant #2, 0.4 mCi/kg

Study	Evidence	Comparator	Comparative Efficacy
Witzig et al. 1999	Phase I/II
Witzig et al. 2002a	Phase III (E-RT-switch-ic)	Rituximab	Superior ORR
Witzig et al. 2002b	Phase II (RT)

Witzig et al. 2002b was intended for patients with rituximab-refractory disease.

Radioimmunotherapy

Rituximab (Rituxan) 250 mg/m² IV once per day on days 1 & 8
Ibritumomab tiuxetan 1.6 mg & Indium-111 5 mCi IV over 10 minutes once on day 1
Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (15 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV over 10 minutes once on day 8, given immediately following rituximab

8-day course

References

Witzig TE, White CA, Wiseman GA, Gordon LI, Emmanouilides C, Raubitschek A, Janakiraman N, Gutheil J, Schilder RJ, Spies S, Silverman DH, Parker E, Grillo-López AJ. Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec;17(12):3793-803. link to original article contains verified protocol PubMed
Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, Pohlman BL, Bartlett NL, Wiseman GA, Padre N, Grillo-López AJ, Multani P, White CA. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2002 May 15;20(10):2453-63. link to original article contains verified protocol PubMed
Wiseman GA, Gordon LI, Multani PS, Witzig TE, Spies S, Bartlett NL, Schilder RJ, Murray JL, Saleh M, Allen RS, Grillo-López AJ, White CA. Ibritumomab tiuxetan radioimmunotherapy for patients with relapsed or refractory non-Hodgkin lymphoma and mild thrombocytopenia: a phase II multicenter trial. Blood. 2002 Jun 15;99(12):4336-42. link to original article PubMed
Witzig TE, Flinn IW, Gordon LI, Emmanouilides C, Czuczman MS, Saleh MN, Cripe L, Wiseman G, Olejnik T, Multani PS, White CA. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin's lymphoma. J Clin Oncol. 2002 Aug 1;20(15):3262-9. link to original article contains verified protocol PubMed

Lenalidomide monotherapy

back to top

Variant #1, up to 12 cycles

Study	Evidence	Comparator	Comparative Efficacy
Leonard et al. 2015 (CALGB 50401)	Randomized Phase II (E-de-esc)	Lenalidomide & Rituximab	Inferior TTP

Chemotherapy

Lenalidomide (Revlimid) as follows:
- Cycle 1: 15 mg PO once per day on days 1 to 21
- Cycles 2 (if prior dose tolerated): 20 mg PO once per day on days 1 to 21
- Cycles 3 to 12 (if prior dose tolerated): 25 mg PO once per day on days 1 to 21

Supportive medications

Aspirin or LMWH recommended for patients at high risk of thrombosis (see paper for details)

28-day cycle for 12 cycles

Variant #2, indefinite

Study	Evidence
Witzig et al. 2009 (NHL-001)	Phase II

Chemotherapy

Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21

28-day cycles

References

Witzig TE, Wiernik PH, Moore T, Reeder C, Cole C, Justice G, Kaplan H, Voralia M, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Vose JM. Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin's Lymphoma. J Clin Oncol. 2009 Nov 10;27(32):5404-9. Epub 2009 Oct 5. link to original article contains verified protocol PubMed
Leonard JP, Jung SH, Johnson J, Pitcher BN, Bartlett NL, Blum KA, Czuczman M, Giguere JK, Cheson BD. Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). J Clin Oncol. 2015 Nov 1;33(31):3635-40. Epub 2015 Aug 24. link to full article contains verified protocol link to PMC article PubMed

Lenalidomide & Rituximab

back to top

Variant #1, len 10

Study	Evidence
Chong et al. 2015	Phase II

Chemotherapy

Lenalidomide (Revlimid) 10 mg PO once per day
Rituximab (Rituxan) as follows:
- Cycle 3: 375 mg/m² IV once per day on days 1, 8, 15, 22

28-day cycles

Variant #2, len dose escalation 15 -> 25 x 12

Study	Evidence	Comparator	Comparative Efficacy
Leonard et al. 2015 (CALGB 50401)	Randomized Phase II (E-esc)	Lenalidomide	Superior TTP

Chemotherapy

Lenalidomide (Revlimid) as follows:
- Cycle 1: 15 mg PO once per day on days 1 to 21
- Cycles 2 (if prior dose tolerated): 20 mg PO once per day on days 1 to 21
- Cycles 3 to 12 (if prior dose tolerated): 25 mg PO once per day on days 1 to 21
Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days 8, 15, 22, 29

Supportive medications

Aspirin or LMWH recommended for patients at high risk of thrombosis (see paper for details)

28-day cycle for 12 cycles

Variant #3, len 20 x 2

Study	Evidence
Tuscano et al. 2014	Phase II

Chemotherapy

Lenalidomide (Revlimid) 20 mg PO once per day on days 1 to 21
Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once on day 15
- Cycle 2: 375 mg/m² IV once per day on days 1, 8, 15, 22

Supportive medications

Allopurinol (Zyloprim) as follows:
- Cycle 1: 300 mg PO once per day
Aspirin 81 mg PO once per day

28-day cycle for 2 cycles

Subsequent treatment

Responders: Lenalidomide maintenance
Patients with less than a CR after induction: more rituximab could be given at the discretion of the treating physician. Dosing details not provided in the reference

Variant #4, len 20 x 12

FDA-recommended dose

Study	Evidence	Comparator	Comparative Efficacy
Leonard et al. 2019 (AUGMENT)	Phase III (E-RT-esc)	Lenalidomide	Superior PFS

Chemotherapy

Lenalidomide (Revlimid) 20 mg PO once per day on days 1 to 21
Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22
- Cycles 2 to 5: 375 mg/m² IV once on day 1

28-day cycle for 12 cycles

References

Tuscano JM, Dutia M, Chee K, Brunson A, Reed-Pease C, Abedi M, Welborn J, O'Donnell RT. Lenalidomide plus rituximab can produce durable clinical responses in patients with relapsed or refractory, indolent non-Hodgkin lymphoma. Br J Haematol. 2014 May;165(3):375-81. Epub 2014 Mar 7. link to original article contains verified protocol PubMed
Chong EA, Ahmadi T, Aqui NA, Svoboda J, Nasta SD, Mato AR, Walsh KM, Schuster SJ. Combination of lenalidomide and rituximab overcomes rituximab resistance in patients with indolent B-cell and mantle cell lymphomas. Clin Cancer Res. 2015 Apr 15;21(8):1835-42. Epub 2015 Jan 28. link to original article contains verified protocol PubMed
Leonard JP, Jung SH, Johnson J, Pitcher BN, Bartlett NL, Blum KA, Czuczman M, Giguere JK, Cheson BD. Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). J Clin Oncol. 2015 Nov 1;33(31):3635-40. Epub 2015 Aug 24. link to full article contains verified protocol link to PMC article PubMed
AUGMENT: Leonard JP, Trneny M, Izutsu K, Fowler NH, Hong X, Zhu J, Zhang H, Offner F, Scheliga A, Nowakowski GS, Pinto A, Re F, Fogliatto LM, Scheinberg P, Flinn IW, Moreira C, Cabeçadas J, Liu D, Kalambakas S, Fustier P, Wu C, Gribben JG; AUGMENT Trial Investigators. AUGMENT: a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019 May 10;37(14):1188-1199. Epub 2019 Mar 21. link to original article PubMed

Obinutuzumab monotherapy

back to top

Variant #1

Study	Evidence	Comparator	Comparative Efficacy
Sehn et al. 2015 (GAUSS)	Randomized Phase II (E-switch-ic)	Rituximab	Might have superior ORR

Chemotherapy

Obinutuzumab (Gazyva) 1000 mg IV once per day on days 1, 8, 15, 22

28-day course

Subsequent treatment

Patients with SD or better: Optional maintenance obinutuzumab

Variant #2

Study	Evidence
Salles et al. 2012 (GAUGUIN)	Phase I/II

Note: Dose here is that recommended by Salles et al. 2013 as having "encouraging activity with an acceptable safety profile"

Chemotherapy

Obinutuzumab (Gazyva) as follows:
- Cycle 1: 1600 mg (diluted to 10 mg/mL) IV once per day on days 1 & 7
- Cycles 2 to 8: 800 mg IV once on day 1
- Initial infusion rate is 50 mg/hour. In the absence of infusion-related reactions (IRRs), the rate is then increased by 50 mg/hour every 30 minutes, up to a maximum of 400 mg/hour.

Supportive medications

Acetaminophen (Tylenol) (no dose specified) PO once per infusion; 30 minutes prior to Obinutuzumab (Gazyva)
Antihistamine (no drug or dose specified) PO once per infusion; 30 minutes prior to Obinutuzumab (Gazyva)
Corticosteroids before Obinutuzumab (Gazyva) for patients at "high risk" of infusion reaction

21-day cycle for 8 cycles

References

GAUGUIN: Salles G, Morschhauser F, Lamy T, Milpied N, Thieblemont C, Tilly H, Bieska G, Asikanius E, Carlile D, Birkett J, Pisa P, Cartron G. Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients. Blood. 2012 May 31;119(22):5126-32. Epub 2012 Mar 19. link to original article PubMed
1. Subgroup analysis: Morschhauser FA, Cartron G, Thieblemont C, Solal-Céligny P, Haioun C, Bouabdallah R, Feugier P, Bouabdallah K, Asikanius E, Lei G, Wenger M, Wassner-Fritsch E, Salles GA. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large B-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2912-9. Epub 2013 Jul 8. link to original article contains verified protocol PubMed
2. Subgroup analysis: Salles GA, Morschhauser F, Solal-Céligny P, Thieblemont C, Lamy T, Tilly H, Gyan E, Lei G, Wenger M, Wassner-Fritsch E, Cartron G. Obinutuzumab (GA101) in patients with relapsed/refractory indolent non-Hodgkin lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2920-6. Epub 2013 Jul 8. link to original article contains verified protocol PubMed
3. Subgroup analysis: Cartron G, de Guibert S, Dilhuydy MS, Morschhauser F, Leblond V, Dupuis J, Mahe B, Bouabdallah R, Lei G, Wenger M, Wassner-Fritsch E, Hallek M. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study. Blood. 2014 Oct 2;124(14):2196-202. Epub 2014 Aug 20. link to original article contains verified protocol PubMed
GAUSS: Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: final analysis of the GAUSS study. J Clin Oncol. 2015 Oct 20;33(30):3467-74. Epub 2015 Aug 17. link to original article] contains verified protocol link to PMC article PubMed

R-CHOP

back to top

R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Variant #1, 3 cycles

Study	Evidence
Illidge et al. 2016 (UK NCRI LG)	Phase II

Dosing details for R-CHOP were not available in the abstract; this is a typical R-CHOP regimen.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for 3 cycles

Subsequent treatment

Ibritumomab tiuxetan consolidation

Variant #2, 6 cycles with prednisone 100 mg

Study	Evidence	Comparator	Comparative Efficacy
Van Oers et al. 2006 (EORTC 20981)	Phase III (E-esc)	CHOP	Superior PFS

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for 6 cycles

Subsequent treatment

Responders (PR or CR): Rituximab maintenance versus no further treatment

Variant #3, 6 cycles with prednisone 100 mg/m²

Study	Evidence
Czuczman et al. 1999	Phase II

Chemotherapy

Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days -6 & -1 (7 and 2 days before cycle 1 day 1)
- Cycles 3 & 5: 375 mg/m² IV once on day -2
- Cycle 6*: 375 mg/m² IV once per day on days 29 & 36 (i.e., what would be cycle 7 days 8 & 15)
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg/m² PO once per day on days 1 to 5

21-day cycle for 6 cycles

References

Czuczman MS, Grillo-López AJ, White CA, Saleh M, Gordon L, LoBuglio AF, Jonas C, Klippenstein D, Dallaire B, Varns C. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol. 1999 Jan;17(1):268-76. link to original article contains protocol PubMed
1. Update: Czuczman MS, Weaver R, Alkuzweny B, Berlfein J, Grillo-López AJ. Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin's lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol. 2004 Dec 1;22(23):4711 to 6. Epub 2004 Oct 13. link to original article PubMed
EORTC 20981: van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van 't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27. link to original article contains verified protocol PubMed
1. Update: van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. Epub 2010 May 3. link to original article contains verified protocol link to PMC article PubMed
Illidge TM, McKenzie HS, Mayes S, Bates A, Davies AJ, Pettengell R, Stanton L, Cozens K, Hampson G, Dive C, Zivanovic M, Tipping J, Gallop-Evans E, Radford JA, Johnson PW. Short duration immunochemotherapy followed by radioimmunotherapy consolidation is effective and well tolerated in relapsed follicular lymphoma: 5-year results from a UK National Cancer Research Institute Lymphoma Group study. Br J Haematol. 2016 Apr;173(2):274-82. Epub 2016 Feb 5. link to original article contains protocol PubMed

R-FCM

back to top

R-FCM: Rituximab, Fludarabine, Cyclophosphamide, Mitoxantrone

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Forstpointner et al. 2004	Phase III (E-esc)	FCM	Seems to have superior PFS

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day -1 (the day before FCM)
Fludarabine (Fludara) 25 mg/m² IV over 30 minutes once per day on days 1 to 3
Cyclophosphamide (Cytoxan) 200 mg/m² IV over 4 hours once per day on days 1 to 3
Mitoxantrone (Novantrone) 8 mg/m² IV over 30 minutes once on day 1

28-day cycle for 4 cycles

Subsequent treatment

PR or CR: Rituximab maintenance versus no further treatment

References

Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Böck HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. Epub 2004 Jul 29. link to original article contains verified protocol PubMed
1. Update: Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group (GLSG). Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. Epub 2006 Aug 31. link to original article contains verified protocol PubMed

Rituximab monotherapy

back to top

Variant #1

Study	Evidence	Comparator	Comparative Efficacy
Hainsworth et al. 2014	Randomized (C)	Bevacizumab & Rituximab	Seems to have inferior PFS

Chemotherapy

Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22
- Cycles 2 to 5: 375 mg/m² IV once on day 1

12-week cycle for 1 cycle, then 2-month cycle for 4 cycles

Variant #2

Study	Evidence	Comparator	Comparative Efficacy
Maloney et al. 1994	Phase 1, <20 pts
Maloney et al. 1997a	Phase II (RT)
Maloney et al. 1997b	Phase 1, <20 pts
McLaughlin et al. 1998	Phase II (RT)
Witzig et al. 2002a	Phase III (C)	Ibritumomab tiuxetan	Inferior ORR
Ghielmini et al. 2004 (SAKK 35/98)	Non-randomized portion of RCT
Hainsworth et al. 2005b	Non-randomized portion of RCT
Sehn et al. 2015 (GAUSS)	Randomized Phase II (C)	Obinutuzumab	Might have inferior ORR

Note: the phase 1 described by Maloney et al. 1994 did not actually employ this dosing level, but is included here for reference purposes.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days 1, 8, 15, 22

Supportive medications

(not explicitly mentioned in all references)
Acetaminophen (Tylenol) 650 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to Rituximab (Rituxan)
Diphenhydramine (Benadryl) 50 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to Rituximab (Rituxan)

4-week course

Subsequent treatment

SAKK 35/98, patients with SD or better at 12 weeks: Rituximab maintenance versus no further treatment
Hainsworth et al. 2005b, patients with SD or better: Rituximab maintenance versus re-treatment with rituximab at time of progression
GAUSS, SD or better: Optional rituximab maintenance

Variant #3

Study	Evidence	Comparator	Comparative Efficacy
Coiffier et al. 2011 (LYM-3001)	Phase III (C)	VR	Seems to have inferior PFS

Chemotherapy

Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22
- Cycles 2 to 6: 375 mg/m² IV once on day 1

Supportive medications

Acetaminophen (Tylenol) 650 mg PO once per infusion; 30 minutes prior to Rituximab (Rituxan)
Diphenhydramine (Benadryl) 50 mg PO once per infusion; 30 minutes prior to Rituximab (Rituxan)

35-day cycle for 6 cycles

Variant #4

Study	Evidence	Comparator	Comparative Efficacy
Kahl et al. 2014 (RESORT)	Phase III (C)	Rituximab; indefinite	Did not meet primary endpoint of TTF

Preceding treatment

Rituximab

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days 1, 8, 15, 22

4-week course, repeated every progression until treatment failure

References

Phase 1: Maloney DG, Liles TM, Czerwinski DK, Waldichuk C, Rosenberg J, Grillo-Lopez A, Levy R. Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood. 1994 Oct 15;84(8):2457-66. link to original article PubMed
Maloney DG, Grillo-López AJ, White CA, Bodkin D, Schilder RJ, Neidhart JA, Janakiraman N, Foon KA, Liles TM, Dallaire BK, Wey K, Royston I, Davis T, Levy R. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood. 1997 Sep 15;90(6):2188-95. link to original article contains protocol PubMed
Phase 1: Maloney DG, Grillo-López AJ, Bodkin DJ, White CA, Liles TM, Royston I, Varns C, Rosenberg J, Levy R. IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma. J Clin Oncol. 1997 Oct;15(10):3266-74. link to original article PubMed
McLaughlin P, Grillo-López AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998 Aug;16(8):2825-33. link to original article contains verified protocol PubMed
Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, Pohlman BL, Bartlett NL, Wiseman GA, Padre N, Grillo-López AJ, Multani P, White CA. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2002 May 15;20(10):2453-63. link to original article contains verified protocol PubMed
SAKK 35/98: Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. link to original article contains protocol PubMed
1. Update: Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. link to original article contains verified protocol PubMed
Hainsworth JD, Litchy S, Shaffer DW, Lackey VL, Grimaldi M, Greco FA. Maximizing therapeutic benefit of rituximab: maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin's lymphoma--a randomized phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Feb 20;23(6):1088-95. Epub 2005 Jan 18. link to original article contains protocol PubMed
Coiffier B, Osmanov EA, Hong X, Scheliga A, Mayer J, Offner F, Rule S, Teixeira A, Walewski J, de Vos S, Crump M, Shpilberg O, Esseltine DL, Zhu E, Enny C, Theocharous P, van de Velde H, Elsayed YA, Zinzani PL; LYM-3001 study investigators. Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial. Lancet Oncol. 2011 Aug;12(8):773-84. Epub 2011 Jul 1. link to original article contains verified protocol PubMed
1. Subgroup analysis: Zinzani PL, Khuageva NK, Wang H, Garicochea B, Walewski J, Van Hoof A, Soubeyran P, Caballero D, Buckstein R, Esseltine DL, Theocharous P, Enny C, Zhu E, Elsayed YA, Coiffier B. Bortezomib plus rituximab versus rituximab in patients with high-risk, relapsed, rituximab-naïve or rituximab-sensitive follicular lymphoma: subgroup analysis of a randomized phase 3 trial. J Hematol Oncol. 2012 Oct 22;5:67. link to original article link to PMC article PubMed
ECOG E4402: Kahl BS, Hong F, Williams ME, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ. Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: Eastern Cooperative Oncology Group protocol E4402. J Clin Oncol. 2014 Oct 1;32(28):3096-102. Epub 2014 Aug 25. link to original article contains verified protocol link to PMC article PubMed
Hainsworth JD, Greco FA, Raefsky EL, Thompson DS, Lunin S, Reeves J Jr, White L, Quinn R, DeBusk LM, Flinn IW. Rituximab with or without bevacizumab for the treatment of patients with relapsed follicular lymphoma. Clin Lymphoma Myeloma Leuk. 2014 Aug;14(4):277-83. Epub 2014 Feb 28. link to original article contains verified protocol PubMed
GAUSS: Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: final analysis of the GAUSS study. J Clin Oncol. 2015 Oct 20;33(30):3467-74. Epub 2015 Aug 17. link to original article] contains verified protocol link to PMC article PubMed

VR

back to top

VR: Velcade (Bortezomib), Rituximab

Variant #1

Study	Evidence	Comparator	Comparative Efficacy
Coiffier et al. 2011 (LYM-3001)	Phase III (E-esc)	Rituximab	Seems to have superior PFS

Chemotherapy

Bortezomib (Velcade) 1.6 mg/m² IV over 3 to 5 seconds once per day on days 1, 8, 15, 22
Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22
- Cycles 2 to 5: 375 mg/m² IV once on day 1

Supportive medications

No routine antiviral prophylaxis was mandated

35-day cycle for 5 cycles

Variant #2

Study	Evidence
Agathocleous et al. 2010	Phase II

Chemotherapy

Bortezomib (Velcade) 1.6 mg/m² IV once per day on days 1, 8, 15, 22
Rituximab (Rituxan) as follows:
- Cycles 1 & 4: 375 mg/m² IV once per day on days 1, 8, 15, 22

35-day cycle for up to 6 cycles

Variant #3

Study	Evidence
de Vos et al. 2009	Phase II

Chemotherapy

Bortezomib (Velcade) 1.6 mg/m² IV once per day on days 1, 8, 15, 22
Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22

35-day cycle for 3 cycles

Variant #4

Study	Evidence
Baiocchi et al. 2011 (OSU-0430)	Phase II, <20 patients reported

Bortezomib dose was initially 1.5 mg/m² but was reduced due to excess grade 3 neurotoxicity.

Chemotherapy

Bortezomib (Velcade) 1.3 mg/m² IV once per day on days 1, 4, 8, 11
Rituximab (Rituxan) as follows:
- Cycle 2 onwards: 375 mg/m² IV once per day on days 1 & 8

21-day cycle for up to 5 cycles.

Subsequent treatment

SD or better: optional VR maintenance

References

de Vos S, Goy A, Dakhil SR, Saleh MN, McLaughlin P, Belt R, Flowers CR, Knapp M, Hart L, Patel-Donnelly D, Glenn M, Gregory SA, Holladay C, Zhang T, Boral AL. Multicenter randomized phase II study of weekly or twice-weekly bortezomib plus rituximab in patients with relapsed or refractory follicular or marginal-zone B-cell lymphoma. J Clin Oncol. 2009 Oct 20;27(30):5023-30. Epub 2009 Sep 21. link to original article contains verified protocol PubMed
Agathocleous A, Rohatiner A, Rule S, Hunter H, Kerr JP, Neeson SM, Matthews J, Strauss S, Montoto S, Johnson P, Radford J, Lister A. Weekly versus twice weekly bortezomib given in conjunction with rituximab, in patients with recurrent follicular lymphoma, mantle cell lymphoma and Waldenström macroglobulinaemia. Br J Haematol. 2010 Nov;151(4):346-53. Epub 2010 Sep 29. link to original article contains verified protocol PubMed
OSU-0430: Baiocchi RA, Alinari L, Lustberg ME, Lin TS, Porcu P, Li X, Johnston JS, Byrd JC, Blum KA. Phase 2 trial of rituximab and bortezomib in patients with relapsed or refractory mantle cell and follicular lymphoma. Cancer. 2011 Jun 1;117(11):2442-51. Epub 2010 Dec 14. link to original article contains verified protocol link to PMC article PubMed
Coiffier B, Osmanov EA, Hong X, Scheliga A, Mayer J, Offner F, Rule S, Teixeira A, Walewski J, de Vos S, Crump M, Shpilberg O, Esseltine DL, Zhu E, Enny C, Theocharous P, van de Velde H, Elsayed YA, Zinzani PL; LYM-3001 study investigators. Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial. Lancet Oncol. 2011 Aug;12(8):773-84. Epub 2011 Jul 1. link to original article contains verified protocol PubMed
1. Subgroup analysis: Zinzani PL, Khuageva NK, Wang H, Garicochea B, Walewski J, Van Hoof A, Soubeyran P, Caballero D, Buckstein R, Esseltine DL, Theocharous P, Enny C, Zhu E, Elsayed YA, Coiffier B. Bortezomib plus rituximab versus rituximab in patients with high-risk, relapsed, rituximab-naïve or rituximab-sensitive follicular lymphoma: subgroup analysis of a randomized phase 3 trial. J Hematol Oncol. 2012 Oct 22;5:67. link to original article link to PMC article PubMed

Relapsed or refractory, non-randomized or retrospective data

Bortezomib monotherapy

back to top

Regimen

Study	Evidence
O'Connor et al. 2005	Phase II, <20 patients reported

Chemotherapy

Bortezomib (Velcade) 1.5 mg/m² IV once per day on days 1, 4, 8, 11

Supportive medications

"Use of antiemetics, erythropoietin, and Filgrastim (Neupogen) was allowed if deemed necessary by the treating physician."

21-day cycles

References

O'Connor OA, Wright J, Moskowitz C, Muzzy J, MacGregor-Cortelli B, Stubblefield M, Straus D, Portlock C, Hamlin P, Choi E, Dumetrescu O, Esseltine D, Trehu E, Adams J, Schenkein D, Zelenetz AD. Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol. 2005 Feb 1;23(4):676-84. Epub 2004 Dec 21. link to original article contains verified protocol PubMed

BVR

back to top

BVR: Bendamustine, Velcade (Bortezomib), Rituximab
VBR: Velcade (Bortezomib), Bendamustine, Rituximab

Variant #1, 1.3/90/375

Study	Evidence
Friedberg et al. 2011	Phase II, <20 patients in this subgroup

Chemotherapy

Bortezomib (Velcade) 1.3 mg/m² IV once per day on days 1, 4, 8, 11, given first
Bendamustine 90 mg/m² IV once per day on days 1 & 4, given third
Rituximab (Rituxan) 375 mg/m² IV once on day 1, given second

Supportive medications

Premedications, antiemetic therapy, and growth factor support per institutional guidelines
No routine antibiotic or antiviral prophylaxis was given

28-day cycle for 6 cycles

Variant #2, 1.6/90/375

Study	Evidence
Fowler et al. 2011 (VERTICAL)	Phase II

Note: Bendamustine was dose-escalated in the first phase of the trial and the 90 mg/m² dose is the MTD.

Chemotherapy

Bortezomib (Velcade) 1.6 mg/m² IV once per day on days 1, 8, 15, 22, given first
Bendamustine 90 mg/m² IV once per day on days 1 & 2, given second
Rituximab (Rituxan) as follows, given third:
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22
- Cycles 2 to 5: 375 mg/m² IV once on day 1

Supportive medications

Antiviral prophylaxis at physician discretion

35-day cycle for 5 cycles

References

Friedberg JW, Vose JM, Kelly JL, Young F, Bernstein SH, Peterson D, Rich L, Blumel S, Proia NK, Liesveld J, Fisher RI, Armitage JO, Grant S, Leonard JP. The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma. Blood. 2011 Mar 10;117(10):2807-12. Epub 2011 Jan 14. link to original article contains verified protocol link to PMC article PubMed
VERTICAL: Fowler N, Kahl BS, Lee P, Matous JV, Cashen AF, Jacobs SA, Letzer J, Amin B, Williams ME, Smith S, Saleh A, Rosen P, Shi H, Parasuraman S, Cheson BD. Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II VERTICAL study. J Clin Oncol. 2011 Sep 1;29(25):3389-95. Epub 2011 Aug 1. link to original article contains verified protocol PubMed

Copanlisib monotherapy

back to top

Variant #1, flat dose

FDA-recommended dose

Study	Evidence	Efficacy
CHRONOS-1 (*)	Phase II	ORR: 59% (95% CI, 49-68)

Note: this is the FDA-recommended dose and the dose used for most of the patients enrolled in this trial; however, the publication to date only details the weight-based dosing (see below).

Chemotherapy

Copanlisib (Aliqopa) 60 mg IV over 60 minutes once per day on days 1, 8, 15

28-day cycles

Variant #2, weight-based

Study	Evidence	Efficacy
Dreyling et al. 2017 (CHRONOS-1)	Phase II (RT)	ORR: 59% (95% CI, 49-68)

Chemotherapy

Copanlisib (Aliqopa) 0.8 mg/kg IV over 60 minutes once per day on days 1, 8, 15

28-day cycles

References

CHRONOS-1: Dreyling M, Morschhauser F, Bouabdallah K, Bron D, Cunningham D, Assouline SE, Verhoef G, Linton K, Thieblemont C, Vitolo U, Hiemeyer F, Giurescu M, Garcia-Vargas J, Gorbatchevsky I, Liu L, Koechert K, Peña C, Neves M, Childs BH, Zinzani PL. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Ann Oncol. 2017 Sep 1;28(9):2169-2178. link to original article link to PMC article contains verified protocol PubMed

Duvelisib monotherapy

back to top

Regimen

Study	Evidence
DYNAMO	Phase II, 83 patients reported

Chemotherapy

Duvelisib 25 mg PO twice per day continuously until progression

References

Flint IW, Miller CB, Ardeshna KM, Tetreault S, Assouline SE, Mayer J, Merli M, Lunin SD, Pettitt AR, Nagy Z, Tournilhac O, Abou-Nassar KE, Crump M, Jacobsen ED, de Vos S, Kelly VM, Shi W, Steelman L, Le N, Weaver DT, Lustgarten S, Wagner-Johnston ND, Zinzani PL. DYNAMO: A Phase II Study of Duvelisib (IPI-145) in Patients With Refractory Indolent Non-Hodgkin Lymphoma. J Clin Oncol. 2019 Apr 10;37(11):912-922. Epub 2019 Feb 11. link to original article contains verified protocol PubMed

FR

back to top

FR: Fludarabine & Rituximab

Regimen

Study	Evidence	Efficacy
Czuczman et al. 2005	Phase II	ORR: 90%

Chemotherapy

Fludarabine (Fludara) as follows:
- Weeks 2, 6, 10, 14, 18, 22: 25 mg/m² IV once per day on days 1 to 5
Rituximab (Rituxan) as follows:
- Weeks 1 & 26: 375 mg/m² IV once per day on days 1 & 4
- Weeks 6, 14, 22: 375 mg/m² IV once 72 hours before day 1

26-week course

References

Czuczman MS, Koryzna A, Mohr A, Stewart C, Donohue K, Blumenson L, Bernstein ZP, McCarthy P, Alam A, Hernandez-Ilizaliturri F, Skipper M, Brown K, Chanan-Khan A, Klippenstein D, Loud P, Rock MK, Benyunes M, Grillo-Lopez A, Bernstein SH. Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma. J Clin Oncol. 2005 Feb 1;23(4):694-704. link to original article contains verified protocol PubMed

Ibrutinib monotherapy

back to top

Regimen

Study	Evidence	Efficacy
Bartlett et al. 2017	Phase II	ORR: 37.5% (95% CI, 23-54)
Gopal et al. 2018 (DAWN)	Phase II	ORR: 21% (95% CI, 14-30)

Chemotherapy

Ibrutinib (Imbruvica) 560 mg PO once per day

28-day cycles

References

Bartlett NL, Costello BA, LaPlant BR, Ansell SM, Kuruvilla JG, Reeder CB, Thye LS, Anderson DM, Krysiak K, Ramirez C, Qi J, Siegel BA, Griffith M, Griffith OL, Gomez F, Fehniger TA. Single-agent ibrutinib in relapsed or refractory follicular lymphoma: a phase 2 consortium trial. Blood. 2018 Jan 11;131(2):182-190. Epub 2017 Oct 26. link to original article contains verified protocol PubMed
DAWN: Gopal AK, Schuster SJ, Fowler NH, Trotman J, Hess G, Hou JZ, Yacoub A, Lill M, Martin P, Vitolo U, Spencer A, Radford J, Jurczak W, Morton J, Caballero D, Deshpande S, Gartenberg GJ, Wang SS, Damle RN, Schaffer M, Balasubramanian S, Vermeulen J, Cheson BD, Salles G. Ibrutinib as treatment for patients with relapsed/refractory follicular lymphoma: results from the open-label, multicenter, phase II DAWN study. J Clin Oncol. 2018 Aug 10;36(23):2405-2412. Epub 2018 May 31. link to original article contains protocol PubMed

Idelalisib monotherapy

back to top

On 3/21/2016 Gilead announced that they were stopping seven clinical trials of idelalisib in patients with CLL, SLL, and iNHL due to excess deaths and increased rates of SAEs. A REMS program has also been announced.

Regimen

Study	Evidence
Gopal et al. 2014 (DELTA)	Phase II (RT)

Chemotherapy

Idelalisib (Zydelig) 150 mg PO twice per day

Continued indefinitely

References

DELTA: Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. PI3Kd inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014 Mar 13;370(11):1008-18. Epub 2014 Jan 22. link to original article contains verified protocol link to PMC article PubMed
1. Update: Abstract: Ajay K. Gopal, MD, Brad S. Kahl, MD, Sven de Vos, MD, PhD, Nina D. Wagner-Johnston, MD, Stephen J. Schuster, MD, Wojciech Jurczak, MD, PhD, Ian W. Flinn, MD, PhD, Christopher R. Flowers, MD, Peter Martin, MD, Andreas Viardot, MD, Kristie A. Blum, MD, Andre Goy, MD, Andrew Davies, BM PhD, Pier Luigi Zinzani, MD, Martin H. Dreyling, MD, PhD, Leanne M. Holes, Bess Sorensen, PhD, Wayne R. Godfrey, MD and Gilles Andre Salles, MD, PhD. Mature Follow up from a Phase 2 Study of PI3K-Delta Inhibitor Idelalisib in Patients with Double (Rituximab and Alkylating agent)-Refractory Indolent B-Cell Non-Hodgkin Lymphoma (iNHL). Blood 2014 124:1708. link to abstract

Inotuzumab ozogamicin monotherapy

back to top

Regimen

Study	Evidence
Goy et al. 2016	Phase II

Chemotherapy

Inotuzumab ozogamicin (Besponsa) 1.8 mg/m² IV once on day 1

28-day cycle for 4 to 8 cycles

References

Goy A, Forero A, Wagner-Johnston N, Christopher Ehmann W, Tsai M, Hatake K, Ananthakrishnan R, Volkert A, Vandendries E, Ogura M. A phase 2 study of inotuzumab ozogamicin in patients with indolent B-cell non-Hodgkin lymphoma refractory to rituximab alone, rituximab and chemotherapy, or radioimmunotherapy. Br J Haematol. 2016 Aug;174(4):571-81. Epub 2016 Apr 22. link to original article PubMed

Lenalidomide, Dexamethasone, Rituximab

back to top

Regimen

Study	Evidence
Ahmadi et al. 2013	Phase II, <20 pts in subgroup

Chemotherapy

Lenalidomide (Revlimid) 10 mg PO once per day
Dexamethasone (Decadron) 8 mg (route not specified) once per day on days 1, 8, 15, 22
Rituximab (Rituxan) as follows:
- Cycle 3: 375 mg/m² IV once per day on days 1, 8, 15, 22

28-day cycles

References

Ahmadi T, Chong EA, Gordon A, Aqui NA, Nasta SD, Svoboda J, Mato AR, Schuster SJ. Combined lenalidomide, low-dose dexamethasone, and rituximab achieves durable responses in rituximab-resistant indolent and mantle cell lymphomas. Cancer. 2014 Jan 15;120(2):222-8. Epub 2013 Oct 7. link to original article contains verified protocol PubMed

Ofatumumab monotherapy

back to top

Regimen

Study	Evidence
Hagenbeek et al. 2008 (Hx-CD20-001)	Phase I/II
Czucman et al. 2012 (405 Study)	Phase II

Note: there was no MTD determined in Hx-CD20-001.

Chemotherapy

Ofatumumab (Arzerra) as follows:
- Cycle 1: 300 mg IV once on day 1, then 1000 mg IV once per day on days 8, 15, 22
- Cycle 2: 1000 mg IV once per day on days 1, 8, 15, 22

Supportive medications

Acetaminophen (Tylenol) 1000 mg (no route specified) before each dose of Ofatumumab (Arzerra)
Cetirizine (Zyrtec) 10 mg (or equivalent) PO before each dose of Ofatumumab (Arzerra)
Prednisolone (Millipred) (or equivalent) 100 mg before dose 1 and 2 of Ofatumumab (Arzerra)

28-day cycle for 2 cycles

References

Hx-CD20-001: Hagenbeek A, Gadeberg O, Johnson P, Pedersen LM, Walewski J, Hellmann A, Link BK, Robak T, Wojtukiewicz M, Pfreundschuh M, Kneba M, Engert A, Sonneveld P, Flensburg M, Petersen J, Losic N, Radford J. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. Blood. 2008 Jun 15;111(12):5486-95. Epub 2008 Apr 4. link to original article PubMed
405 Study: Czuczman MS, Fayad L, Delwail V, Cartron G, Jacobsen E, Kuliczkowski K, Link BK, Pinter-Brown L, Radford J, Hellmann A, Gallop-Evans E, DiRienzo CG, Goldstein N, Gupta I, Jewell RC, Lin TS, Lisby S, Schultz M, Russell CA, Hagenbeek A; 405 Study Investigators. Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study. Blood. 2012 Apr 19;119(16):3698-704. Epub 2012 Mar 2. link to original article contains verified protocol PubMed

PEP-C

back to top

PEP-C: Prednisone, Etoposide, Procarbazine, Cyclophosphamide

Regimen

Study	Evidence
Coleman et al. 2008	Retrospective

Chemotherapy, induction phase

Prednisone (Sterapred) 20 mg PO once per day after breakfast
Etoposide (Vepesid) 50 mg PO once per day after dinner
Procarbazine (Matulane) 50 mg PO once per day at bedtime
Cyclophosphamide (Cytoxan) 50 mg PO once per day after lunch

Supportive medications

Ondansetron (Zofran) (dose not specified, presumably PO) with each Procarbazine (Matulane) dose

Continue until WBC count less than 3 x 10⁹/L, hold until WBC count recovery, then titrate in maintenance phase per paper (see publication for details)

Chemotherapy, maintenance phase

Same medications and doses given per day as used in the induction phase, but the number of days per week they are used is titrated to maintain a WBC count of at least 3 x 10⁹/L; for example, 5 out of 7 days, every other day, once per week, etc.

References

Retrospective: Coleman M, Martin P, Ruan J, Furman R, Niesvizky R, Elstrom R, George P, Kaufman TP, Leonard JP. Prednisone, etoposide, procarbazine, and cyclophosphamide (PEP-C) oral combination chemotherapy regimen for recurring/refractory lymphoma: low-dose metronomic, multidrug therapy. Cancer. 2008 May 15;112(10):2228-32. link to original article contains verified protocol PubMed

R-CVP

back to top

R-CVP: Rituximab, Cyclophosphamide, Vincristine, Prednisone

Regimen

Study	Evidence
Illidge et al. 2016 (UK NCRI LG)	Phase II

Dosing details for R-CVP were not available in the abstract; this is a typical R-CVP regimen.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

21-day cycle for 3 cycles

Subsequent treatment

Ibritumomab tiuxetan consolidation

References

UK NCRI LG: Illidge TM, McKenzie HS, Mayes S, Bates A, Davies AJ, Pettengell R, Stanton L, Cozens K, Hampson G, Dive C, Zivanovic M, Tipping J, Gallop-Evans E, Radford JA, Johnson PW. Short duration immunochemotherapy followed by radioimmunotherapy consolidation is effective and well tolerated in relapsed follicular lymphoma: 5-year results from a UK National Cancer Research Institute Lymphoma Group study. Br J Haematol. 2016 Apr;173(2):274-82. Epub 2016 Feb 5. link to original article contains protocol PubMed

R-DexaBEAM

back to top

R-DexaBEAM: Rituximab, Dexamethasone, BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan

Regimen

Study	Evidence
Kirschey et al. 2014	Phase II

Note: the dosing in the manuscript is different than below. The below are the correct doses as verified by the authors.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days 1 & 8
Dexamethasone (Decadron) 8 mg PO three times per day on days 1 to 10
Carmustine (BCNU) 60 mg/m² IV once on day 3
Etoposide (Vepesid) 75 mg/m² IV once per day on days 4 to 7
Cytarabine (Ara-C) 100 mg/m² IV twice per day on days 4 to 7
Melphalan (Alkeran) 20 mg/m² IV once on day 2

3- to 4-week cycle for 2 cycles

Subsequent treatment

R-BEAM with autologous hematopoietic stem cell transplant or R-TBI/Cy with autologous hematopoietic stem cell transplant

References

Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. link to original article contains verified protocol PubMed

R-FND

back to top

R-FND: Rituximab, Fludarabine, Novantrone, Dexamethasone

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Nastoupil et al. 2017	Randomized (E-switch-ic)	FND, then R	Did not meet primary endpoint of CR rate

Note: although this is the experimental arm of a negative study, the concurrent approach is the standard approach now.

Chemotherapy

Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days 1 & 8
- Cycles 2 to 5: 375 mg/m² IV once on day 1
Fludarabine (Fludara) 25 mg/m² IV once per day on days 2 to 4
Mitoxantrone (Novantrone) 10 mg/m² IV once on day 2
Dexamethasone (Decadron) 20 mg IV or PO once per day on days 1 to 5

28-day cycle for up to 8 cycles

Subsequent treatment

Interferon alfa maintenance

References

Review: Hagemeister F, Cabanillas F, Coleman M, Gregory SA, Zinzani PL. The role of mitoxantrone in the treatment of indolent lymphomas. Oncologist. 2005 Feb;10(2):150-9. link to original article PubMed content property of HemOnc.org
Retrospective: Liu Q, Fayad L, Cabanillas F, Hagemeister FB, Ayers GD, Hess M, Romaguera J, Rodriguez MA, Tsimberidou AM, Verstovsek S, Younes A, Pro B, Lee MS, Ayala A, McLaughlin P. Improvement of overall and failure-free survival in stage IV follicular lymphoma: 25 years of treatment experience at The University of Texas M.D. Anderson Cancer Center. J Clin Oncol. 2006 Apr 1;24(10):1582-9. link to original article PubMed
Nastoupil LJ, McLaughlin P, Feng L, Neelapu SS, Samaniego F, Hagemeister FB, Ayala A, Romaguera JE, Goy AH, Neal E, Wang M, Fayad L, Fanale MA, Oki Y, Westin JR, Rodriguez MA, Cabanillas F, Fowler NH. High ten-year remission rates following rituximab, fludarabine, mitoxantrone and dexamethasone (R-FND) with interferon maintenance in indolent lymphoma: results of a randomized study. Br J Haematol. 2017 Apr;177(2):263-270. Epub 2017 Mar 24. link to original article link to PMC article contains verified protocol PubMed

R-INO

back to top

R-INO: Rituximab, INOtuzumab ozogamicin

Regimen

Study	Evidence	Efficacy
Fayad et al. 2013 (B1931004)	Phase I/II	ORR: 87%

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1
Inotuzumab ozogamicin (Besponsa) 1.8 mg/m² IV once on day 2

28-day cycle for up to 8 cycles

References

B1931004: Fayad L, Offner F, Smith MR, Verhoef G, Johnson P, Kaufman JL, Rohatiner A, Advani A, Foran J, Hess G, Coiffier B, Czuczman M, Giné E, Durrant S, Kneissl M, Luu KT, Hua SY, Boni J, Vandendries E, Dang NH. Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with rituximab. J Clin Oncol. 2013 Feb 10;31(5):573-83. Epub 2013 Jan 7. link to original article link to PMC article contains verified protocol PubMed

Temsirolimus monotherapy

back to top

Regimen

Study	Evidence
Smith et al. 2010	Phase II

Chemotherapy

Temsirolimus (Torisel) 25 mg IV over 30 minutes once per day on days 1, 8, 15, 22

28-day cycle for at least 2 cycles

References

Smith SM, van Besien K, Karrison T, Dancey J, McLaughlin P, Younes A, Smith S, Stiff P, Lester E, Modi S, Doyle LA, Vokes EE, Pro B. Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: The University of Chicago phase II consortium. J Clin Oncol. 2010 Nov 1;28(31):4740-6. Epub 2010 Sep 13. link to original article contains verified protocol link to PMC article PubMed

Vorinostat monotherapy

back to top

Regimen

Study	Evidence
Kirschbaum et al. 2011	Phase II, <20 pts in subgroup
Ogura et al. 2014	Phase II

Chemotherapy

Vorinostat (Zolinza) 200 mg PO twice per day on days 1 to 14

21-day cycles

References

Kirschbaum M, Frankel P, Popplewell L, Zain J, Delioukina M, Pullarkat V, Matsuoka D, Pulone B, Rotter AJ, Espinoza-Delgado I, Nademanee A, Forman SJ, Gandara D, Newman E. Phase II study of vorinostat for treatment of relapsed or refractory indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol. 2011 Mar 20;29(9):1198-203. Epub 2011 Feb 7. link to original article contains verified protocol link to PMC article PubMed
Ogura M, Ando K, Suzuki T, Ishizawa K, Oh SY, Itoh K, Yamamoto K, Au WY, Tien HF, Matsuno Y, Terauchi T, Yamamoto K, Mori M, Tanaka Y, Shimamoto T, Tobinai K, Kim WS. A multicentre phase II study of vorinostat in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma. Br J Haematol. 2014 Jun;165(6):768-776. Epub 2014 Mar 12. link to original article contains verified protocol link to PMC article PubMed

Vorinostat & Rituximab

back to top

Regimen

Study	Evidence
Chen et al. 2015 (CoH 07195)	Phase II, <20 patients in this subgroup

Chemotherapy

Vorinostat (Zolinza) 200 mg PO twice per day on days 1 to 14
Rituximab (Rituxan) 375 mg/m² IV once on day 1

21-day cycles until progression or two cycles past documented CR

References

CoH 07195: Chen R, Frankel P, Popplewell L, Siddiqi T, Ruel N, Rotter A, Thomas SH, Mott M, Nathwani N, Htut M, Nademanee A, Forman SJ, Kirschbaum M. A phase II study of vorinostat and rituximab for treatment of newly diagnosed and relapsed/refractory indolent non-Hodgkin lymphoma. Haematologica. 2015 Mar;100(3):357-62. Epub 2015 Jan 16. link to original article contains verified protocol link to PMC article PubMed

VR-CP

back to top

VR-CP: Velcade (Bortezomib), Rituximab, Cyclophosphamide, Prednisone

Regimen

Study	Evidence
Craig et al. 2014 (C05012)	Phase II

Chemotherapy

Bortezomib (Velcade) 1.6 mg/m² IV once per day on days 1 & 8
Rituximab (Rituxan) 375 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 1000 mg/m² IV once on day 1
Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

Supportive medications

Antiviral prophylaxis against VZV recommended for all patients

21-day cycle for 6 cycles

References

C05012: Craig M, Hanna WT, Cabanillas F, Chen CS, Esseltine DL, Neuwirth R, O'Connor OA. Phase II study of bortezomib in combination with rituximab, cyclophosphamide and prednisone with or without doxorubicin followed by rituximab maintenance in patients with relapsed or refractory follicular lymphoma. Br J Haematol. 2014 Sep;166(6):920-8. Epub 2014 Jul 9. link to original article contains verified protocol PubMed

Consolidation after subsequent lines of therapy

FCR, then allo HSCT

back to top

FCR: Fludarabine, Cyclophosphamide, Rituximab

Regimen

Study	Evidence
Khouri et al. 2001	Phase II

Details are best described in the 2008 update.

Chemotherapy

Fludarabine (Fludara) 30 mg/m² IV once per day on days -5 to -3
Cyclophosphamide (Cytoxan) 750 mg/m² IV once per day on days -5 to -3

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV once on day -13, then 1000 mg/m² IV once per day on days -6, +1, +8

Immunotherapy

Allogeneic stem cells transfused on day 0

GVHD prophylaxis

Antithymocyte globulin, horse ATG (Atgam) by the following donor-based criteria:
- Matched unrelated donor: 15 mg/kg IV once per day on days -5 to -3
Tacrolimus (Prograf) adjusted to level of 5 to 10 ng/mL for 6 months in patients in remission
Methotrexate (MTX) by the following donor-based criteria:
- Related donors: 5 mg/m² IV once per day on days +1, +3, +6
- Unrelated donors: 5 mg/m² IV once per day on days +1, +3, +6, +11

One course

Immunotherapy

Allogeneic stem cells

Stem cells transfused on day 0

References

Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB, Korbling M, Younes A, Ippoliti C, Gajewski JL, McLaughlin P, Anderlini P, Donato ML, Cabanillas FF, Champlin RE. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood. 2001 Dec 15;98(13):3595-9. link to original article PubMed
1. Update: Khouri IF, McLaughlin P, Saliba RM, Hosing C, Korbling M, Lee MS, Medeiros LJ, Fayad L, Samaniego F, Alousi A, Anderlini P, Couriel D, de Lima M, Giralt S, Neelapu SS, Ueno NT, Samuels BI, Hagemeister F, Kwak LW, Champlin RE. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood. 2008 Jun 15;111(12):5530-6. Epub 2008 Apr 14. Erratum in: Blood. 2009 Feb 12;113(7):1613. link to original article contains verified protocol link to PMC article PubMed
2. Update: Khouri IF, Saliba RM, Erwin WD, Samuels BI, Korbling M, Medeiros LJ, Valverde R, Alousi AM, Anderlini P, Bashir Q, Ciurea S, Gulbis AM, de Lima M, Hosing C, Kebriaei P, Popat UR, Fowler N, Neelapu SS, Samaniego F, Champlin RE, Macapinlac HA. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood. 2012 Jun 28;119(26):6373-8. Epub 2012 May 14. link to original article contains verified protocol link to PMC article PubMed

Ibritumomab tiuxetan monotherapy

back to top

Regimen

Study	Evidence
Illidge et al. 2016 (UK NCRI LG)	Phase II

Preceding treatment

R-CHOP x 3 or R-CVP x 3

Radioimmunotherapy

Rituximab (Rituxan) 250 mg/m² IV once per day on days 1 & 8
Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 15 MBq/kg (maximum dose of 1200 MBq) IV once on day 8, given immediately after rituximab

8-day course

References

UK NCRI LG: Illidge TM, McKenzie HS, Mayes S, Bates A, Davies AJ, Pettengell R, Stanton L, Cozens K, Hampson G, Dive C, Zivanovic M, Tipping J, Gallop-Evans E, Radford JA, Johnson PW. Short duration immunochemotherapy followed by radioimmunotherapy consolidation is effective and well tolerated in relapsed follicular lymphoma: 5-year results from a UK National Cancer Research Institute Lymphoma Group study. Br J Haematol. 2016 Apr;173(2):274-82. Epub 2016 Feb 5. link to original article contains protocol PubMed

Observation

back to top

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Ghielmini et al. 2004 (SAKK 35/98)	Phase III (C)	Rituximab	Seems to have inferior EFS
Forstpointner et al. 2004	Phase III (C)	Rituximab	Seems to have inferior PFS
Van Oers et al. 2006 (EORTC 20981)	Phase III (C)	Rituximab	Seems to have inferior OS
Pettengell et al. 2013 (EBMT Lym-1)	Phase III (C)	Rituximab	Seems to have inferior PFS

No further treatment after second-line therapy.

Preceding treatment

SAKK 35/98: R x 4
Forstpointner et al. 2004: R-FCM x 4 versus FCM x 4
EORTC 20981: CHOP versus R-CHOP
EBMT Lym-1: BEAM with auto HSCT

References

SAKK 35/98: Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. link to original article contains protocol PubMed
1. Update: Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. link to original article contains verified protocol PubMed
Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Böck HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. Epub 2004 Jul 29. link to original article contains verified protocol PubMed
1. Update: Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group (GLSG). Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. Epub 2006 Aug 31. link to original article contains verified protocol PubMed
EORTC 20981: van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van 't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27. link to original article contains verified protocol PubMed
1. Update: van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. Epub 2010 May 3. link to original article contains verified protocol link to PMC article PubMed
EBMT Lym-1: Pettengell R, Schmitz N, Gisselbrecht C, Smith G, Patton WN, Metzner B, Caballero D, Tilly H, Walewski JA, Bence-Bruckler I, To B, Geisler CH, Schots R, Kimby E, Taverna CJ, Kozák T, Dreger P, Uddin R, Ruiz de Elvira C, Goldstone AH. Rituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma: a prospective randomized trial from the lymphoma working party of the European group for blood and marrow transplantation. J Clin Oncol. 2013 May 1;31(13):1624-30. Epub 2013 Apr 1. link to original article PubMed

Rituximab monotherapy, abbreviated course

back to top

Maintenance regimens of less than one year duration or less than 12 total doses.

Variant #1, 4 doses

Study	Evidence	Comparator	Comparative Efficacy
Ghielmini et al. 2004 (SAKK 35/98)	Phase III (E-esc)	Observation	Seems to have superior EFS
Pettengell et al. 2013 (EBMT Lym-1)	Phase III (E-esc)	Observation	Seems to have superior EFS

Note: SAKK 35/98 specifies that treatment is to be given at week 12, month 5, 7, 9. Pettengell et al. 2013 does not specify when the maintenance rituximab is to begin post-auto HSCT.

Preceding treatment

SAKK 35/98: Rituximab re-induction
EBMT Lym-1: BEAM with auto HSCT

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

2-month cycle for 4 cycles

Variant #2, 8 doses

Study	Evidence	Comparator	Comparative Efficacy
Forstpointner et al. 2004	Phase III (E-esc)	Observation	Seems to have superior PFS

Note: first cycle begins 3 months after completion of salvage therapy.

Preceding treatment

R-FCM x 4 versus FCM x 4

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days 1, 8, 15, 22

6-month cycle for 2 cycles

References

SAKK 35/98: Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. link to original article contains protocol PubMed
1. Update: Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. link to original article contains verified protocol PubMed
Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Böck HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. Epub 2004 Jul 29. link to original article contains verified protocol PubMed
1. Update: Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group (GLSG). Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. Epub 2006 Aug 31. link to original article contains verified protocol PubMed
EBMT Lym-1: Pettengell R, Schmitz N, Gisselbrecht C, Smith G, Patton WN, Metzner B, Caballero D, Tilly H, Walewski JA, Bence-Bruckler I, To B, Geisler CH, Schots R, Kimby E, Taverna CJ, Kozák T, Dreger P, Uddin R, Ruiz de Elvira C, Goldstone AH. Rituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma: a prospective randomized trial from the lymphoma working party of the European group for blood and marrow transplantation. J Clin Oncol. 2013 May 1;31(13):1624-30. Epub 2013 Apr 1. link to original article PubMed

R-BEAM, then auto HSCT

back to top

R-BEAM: Rituximab, BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan

Regimen

Study	Evidence
Kirschey et al. 2014	Phase II

A minimum number of 2 × 10⁶/kg bw CD34-positive cells were required to proceed.

Preceding treatment

R-DexaBEAM x 2

Autologous HSCT conditioning regimens

References

Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. link to original article contains verified protocol PubMed

R-TBI/Cy, then auto HSCT

back to top

R-TBI/Cy: Rituximab, Total, Body, Irradiation, Cyclophosphamide

Regimen

Study	Evidence
Kirschey et al. 2014	Phase II

Preceding treatment

R-DexaBEAM x 2

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days -8 & -2

Chemotherapy

Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2

Radiotherapy

Total body irradiation (TBI) with a total dose of 1200 cGy over 3 days (days -6 to -4) in fractions

Supportive therapy

Autologous stem cells re-infused on day 0

One course

Stem cells reinfused on day 0

References

Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. link to original article contains verified protocol PubMed

Cyclophosphamide & TBI, then auto HSCT

back to top

Cy/TBI: Cyclophosphamide & Total Body Irradiation

Regimen

Study	Evidence	Comparator	Comparative Efficacy
Schouten et al. 2003 (CUP)	Phase III (E-esc)	CHOP x 3	Might have superior OS

Chemotherapy

Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2

Radiotherapy

Total body irradiation (TBI) 1200 cGy in fractions on days –6 to –4 (pulmonary dosage was limited to 800 cGy)

Supportive therapy

Autologous stem cells re-infused on day 0

One course

References

CUP: Schouten HC, Qian W, Kvaloy S, Porcellini A, Hagberg H, Johnsen HE, Doorduijn JK, Sydes MR, Kvalheim G. High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial. J Clin Oncol. 2003 Nov 1;21(21):3918-27. Epub 2003 Sep 29. link to original article PubMed

(90)YFC, then allo HSCT

back to top

(90)YFC: Ibritumomab tiuxetan, Fludarabine, Cyclophosphamide

Regimen

Study	Evidence
Khouri et al. 2001	Non-randomized

Targeted therapy

Rituximab (Rituxan) 250 mg/m² IV once per day on days -14 & -7

Radioconjugate therapy

Ibritumomab tiuxetan & Indium-111 5 mCi IV once on day -14 for dosimetry
Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (15 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV once on day -7

Chemotherapy

Fludarabine (Fludara) 30 mg/m² IV once per day on days -5 to -3
Cyclophosphamide (Cytoxan) 750 mg/m² IV once per day on days -5 to -3

Immunotherapy

Allogeneic stem cells transfused on day 0

GVHD prophylaxis

Antithymocyte globulin, rabbit ATG (Thymoglobulin) by the following donor-based criteria:
- Matched unrelated or mismatched donors: 1 mg/kg IV once per day on days -2 & -1
Tacrolimus (Prograf)
Methotrexate (MTX)

One course

Immunotherapy

Allogeneic stem cells

Stem cells transfused on day 0

References

Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB, Korbling M, Younes A, Ippoliti C, Gajewski JL, McLaughlin P, Anderlini P, Donato ML, Cabanillas FF, Champlin RE. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood. 2001 Dec 15;98(13):3595-9. link to original article PubMed
1. Update: Khouri IF, McLaughlin P, Saliba RM, Hosing C, Korbling M, Lee MS, Medeiros LJ, Fayad L, Samaniego F, Alousi A, Anderlini P, Couriel D, de Lima M, Giralt S, Neelapu SS, Ueno NT, Samuels BI, Hagemeister F, Kwak LW, Champlin RE. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood. 2008 Jun 15;111(12):5530-6. Epub 2008 Apr 14. Erratum in: Blood. 2009 Feb 12;113(7):1613. link to original article contains verified protocol link to PMC article PubMed
2. Update: Khouri IF, Saliba RM, Erwin WD, Samuels BI, Korbling M, Medeiros LJ, Valverde R, Alousi AM, Anderlini P, Bashir Q, Ciurea S, Gulbis AM, de Lima M, Hosing C, Kebriaei P, Popat UR, Fowler N, Neelapu SS, Samaniego F, Champlin RE, Macapinlac HA. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood. 2012 Jun 28;119(26):6373-8. Epub 2012 May 14. link to original article contains verified protocol link to PMC article PubMed

Maintenance after subsequent lines of therapy

Lenalidomide monotherapy

back to top

Regimen

Study	Evidence
Tuscano et al. 2014	Phase II

Preceding treatment

Lenalidomide & Rituximab

Chemotherapy

Lenalidomide (Revlimid) 20 mg PO once per day on days 1 to 21

Supportive medications

Aspirin 81 mg PO once per day

28-day cycles

References

Tuscano JM, Dutia M, Chee K, Brunson A, Reed-Pease C, Abedi M, Welborn J, O'Donnell RT. Lenalidomide plus rituximab can produce durable clinical responses in patients with relapsed or refractory, indolent non-Hodgkin lymphoma. Br J Haematol. 2014 May;165(3):375-81. Epub 2014 Mar 7. link to original article contains verified protocol PubMed

Obinutuzumab monotherapy

back to top

Regimen

Study	Evidence
Sehn et al. 2015 (GAUSS)	Non-randomized portion of RCT
Sehn et al. 2016 (GADOLIN)	Non-randomized portion of RCT

Preceding treatment

GAUSS: Obinutuzumab induction
GADOLIN: Bendamustine & Obinutuzumab x 6

Chemotherapy

Obinutuzumab (Gazyva) 1000 mg IV once on day 1

2-month cycle for 12 cycles

References

GAUSS: Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: final analysis of the GAUSS study. J Clin Oncol. 2015 Oct 20;33(30):3467-74. Epub 2015 Aug 17. link to original article] contains verified protocol link to PMC article PubMed
GADOLIN: Sehn LH, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben J, Lennard A, Lugtenburg PJ, Dimier N, Wassner-Fritsch E, Fingerle-Rowson G, Cheson BD. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1081-93. Epub 2016 Jun 23. link to original article contains protocol PubMed
1. Update: Cheson BD, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben JG, Lennard A, Lugtenburg PJ, Fingerle-Rowson G, Mattiello F, Knapp A, Sehn LH. Overall survival benefit in patients with rituximab-refractory indolent non-Hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study. J Clin Oncol. 2018 Aug 1;36(22):2259-2266. Epub 2018 Mar 27. link to original article PubMed

Rituximab monotherapy, extended course

back to top

Maintenance regimens of one to two years duration or 12 to 16 total doses.

Variant #1, 3-month cycles

Study	Evidence	Comparator	Comparative Efficacy
Van Oers et al. 2006 (EORTC 20981)	Phase III (E-esc)	Observation	Seems to have superior OS

Preceding treatment

CHOP versus R-CHOP

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

3-month cycle for up to 8 cycles (2 years)

Variant #2, 2-month cycles

Study	Evidence
Witzens-Harig et al. 2014 (MAXIMA)	Non-randomized
Sehn et al. 2015 (GAUSS)	Non-randomized portion of RCT

Preceding treatment

MAXIMA: Rituximab monotherapy or rituximab and chemotherapy (Most patients, 62%, received an anthracycline-based regimen)
GAUSS: Rituximab

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

2-month cycle for up to 12 cycles (2 years)

References

EORTC 20981: van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van 't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27. link to original article contains verified protocol PubMed
1. Update: van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. Epub 2010 May 3. link to original article contains verified protocol link to PMC article PubMed
Witzens-Harig M, Foá R, Di Rocco A, van Hazel G, Chamone DF, Rowe JM, Arcaini L, Poddubnaya I, Ho AD, Ivanova V, Vranovsky A, Thurley D, Oertel S. Maintenance with rituximab is safe and not associated with severe or uncommon infections in patients with follicular lymphoma: results from the phase IIIb MAXIMA study. Ann Hematol. 2014 Oct;93(10):1717-24. Epub 2014 May 14. Erratum in: Ann Hematol. 2014 Oct;93(10):1807. link to original article contains verified protocol PubMed
GAUSS: Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: final analysis of the GAUSS study. J Clin Oncol. 2015 Oct 20;33(30):3467-74. Epub 2015 Aug 17. link to original article] contains verified protocol link to PMC article PubMed

VR

back to top

VR: Velcade (Bortezomib), Rituximab

Regimen

Study	Evidence
Baiocchi et al. 2011 (OSU-0430)	Phase II, <20 patients reported

Preceding treatment

VR re-induction

Chemotherapy

Bortezomib (Velcade) 1.3 mg/m² IV once per day on days 1 & 8
Rituximab (Rituxan) 375 mg/m² IV once per day on days 1 & 8

6-month cycle for up to 4 cycles (2 years)

References

OSU-0430: Baiocchi RA, Alinari L, Lustberg ME, Lin TS, Porcu P, Li X, Johnston JS, Byrd JC, Blum KA. Phase 2 trial of rituximab and bortezomib in patients with relapsed or refractory mantle cell and follicular lymphoma. Cancer. 2011 Jun 1;117(11):2442-51. Epub 2010 Dec 14. link to original article contains verified protocol link to PMC article PubMed

Prognosis

Follicular lymphoma international prognostic index (FLIPI - 1)

back to top

Each category is assigned 0 or 1 points:

Age
- Less than 60 years (0 points)
- Greater than or equal to 60 years (1 point)
Ann Arbor stage
- I or II (0 points)
- III or IV (1 point)
Hemoglobin level
- Less than 12 g/dL (1 point)
- Greater than or equal to 12 g/dL (0 points)
Serum LDH level (note that reference ranges can vary widely!)
- Less than or equal to upper limit of normal (0 points)
- Greater than upper limit of normal (1 point)
Number of nodal sites
- Less than 5 (0 points)
- Greater than or equal to 5 (1 point)

Risk stratification:

0 or 1 points: Low risk
2 points: Intermediate risk
Greater than or equal to 3 points: High risk

References

Solal-Céligny P, Roy P, Colombat P, White J, Armitage JO, Arranz-Saez R, Au WY, Bellei M, Brice P, Caballero D, Coiffier B, Conde-Garcia E, Doyen C, Federico M, Fisher RI, Garcia-Conde JF, Guglielmi C, Hagenbeek A, Haïoun C, LeBlanc M, Lister AT, Lopez-Guillermo A, McLaughlin P, Milpied N, Morel P, Mounier N, Proctor SJ, Rohatiner A, Smith P, Soubeyran P, Tilly H, Vitolo U, Zinzani PL, Zucca E, Montserrat E. Follicular lymphoma international prognostic index. Blood. 2004 Sep 1;104(5):1258-65. Epub 2004 May 4. link to original article PubMed

Follicular lymphoma international prognostic index (FLIPI - 2)

back to top

Each category is assigned 0 or 1 points:

Age
- Less than 60 years (0 points)
- Greater than or equal to 60 years (1 point)
Hemoglobin level
- Less than 12 g/dL (1 point)
- Greater than or equal to 12 g/dL (0 points)
β2-microglobulin level (note that reference ranges can vary)
- Less than or equal to upper limit of normal (0 points)
- Greater than upper limit of normal (1 point)
Longest diameter of the largest involved node
- Less than or equal to 6 cm (0 points)
- Greater than 6 cm (1 point)
Bone marrow involvement
- No (0 points)
- Yes (1 point)

Risk stratification:

0 points: Low risk
1 or 2 points: Intermediate risk
Greater than or equal to 3 points: High risk

References

Federico M, Bellei M, Marcheselli L, Luminari S, Lopez-Guillermo A, Vitolo U, Pro B, Pileri S, Pulsoni A, Soubeyran P, Cortelazzo S, Martinelli G, Martelli M, Rigacci L, Arcaini L, Di Raimondo F, Merli F, Sabattini E, McLaughlin P, Solal-Céligny P. Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. J Clin Oncol. 2009 Sep 20;27(27):4555-62. Epub 2009 Aug 3. link to original article PubMed

Response criteria

NCI Sponsored International Working Group Criteria (1999)

Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351. link to original article PubMed

Investigational agents

These are drugs under study with at least some promising results for this disease.

@@ Line 1: / Line 1: @@
 {| class="wikitable" style="text-align:center; width:50%;"
-!colspan="2" align="center" style="color:white; font-size:125%; background-color:#de2d26"|'''Section editor'''
+! colspan="2" align="center" style="color:white; font-size:125%; background-color:#de2d26" |'''Section editor'''
 |-
-|style="background-color:#F0F0F0"|[[File:Sanjaisharma.jpg|frameless|upright=0.3|center]]
+| style="background-color:#F0F0F0" |[[File:Sanjaisharma.jpg|frameless|upright=0.3|center]]
 |<big>[[User:Sanjaisharma|Sanjai Sharma, MD]]<br>Sequoia Regional Cancer Center<br>Visalia, CA</big>
 |-
@@ Line 19: / Line 19: @@
 ==[http://www.esmo.org/ ESMO]==
 ===Current===
 *'''2016:''' Dreyling et al. [https://www.esmo.org/Guidelines/Haematological-Malignancies/Newly-Diagnosed-and-Relapsed-Follicular-Lymphoma Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 ===Older===
 *'''2014:''' Dreyling et al. [https://academic.oup.com/annonc/article-lookup/doi/10.1093/annonc/mdu200 Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/25122695 PubMed]
 *'''2013:''' Ghielmini et al. [http://annonc.oxfordjournals.org/content/24/3/561.full.pdf+html ESMO Guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL)] [https://www.ncbi.nlm.nih.gov/pubmed/23175624 PubMed]
 ==[https://www.nccn.org/ NCCN]==
 *[https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf NCCN Guidelines - B-cell Lymphomas]
@@ Line 36: / Line 39: @@
 ===Regimen {{#subobject:4eac5|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13021/full Samaniego et al. 2014 (MDACC 2005-0512)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Radioimmunotherapy====
 *[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8, '''given first'''
-*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] '''given second''', as follows:
+*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] '''given second''', as follows:
 **Platelet count greater than 150 x 10<sup>9</sup>/L: 14.8 MBq/kg (maximum dose of 1184 MBq) IV once on day 8
 **Platelet count between 100 and 149 x 10<sup>9</sup>/L: 11.1 MBq/kg (maximum dose of 1184 MBq) IV once on day 8
 ===References===
 <!-- Study results were presented at 12th International Conference on Malignant Lymphoma Lugano, Switzerland, 2013. -->
-# '''MDACC 2005-0512:''' Samaniego F, Berkova Z, Romaguera JE, Fowler N, Fanale MA, Pro B, Shah JJ, McLaughlin P, Sehgal L, Selvaraj V, Braun FK, Mathur R, Feng L, Neelapu SS, Kwak LW. 90Y-ibritumomab tiuxetan radiotherapy as first-line therapy for early stage low-grade B-cell lymphomas, including bulky disease. Br J Haematol. 2014 Oct;167(2):207-13. Epub 2014 Jul 8. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13021/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25040450 PubMed]
+#'''MDACC 2005-0512:''' Samaniego F, Berkova Z, Romaguera JE, Fowler N, Fanale MA, Pro B, Shah JJ, McLaughlin P, Sehgal L, Selvaraj V, Braun FK, Mathur R, Feng L, Neelapu SS, Kwak LW. 90Y-ibritumomab tiuxetan radiotherapy as first-line therapy for early stage low-grade B-cell lymphomas, including bulky disease. Br J Haematol. 2014 Oct;167(2):207-13. Epub 2014 Jul 8. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13021/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25040450 PubMed]
 ==Radiation therapy {{#subobject:6298df|Regimen=1}}==
@@ Line 60: / Line 66: @@
 ===Regimen {{#subobject:904206|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19930401)71:7%3C2342::AID-CNCR2820710728%3E3.0.CO;2-I Yahalom et al. 1993]
@@ Line 92: / Line 98: @@
 ''This is the current "standard dose" radiotherapy - dose varies per protocol and location radiated.''
 ====Radiotherapy====
 *[[External beam radiotherapy]] 24 to 36 Gy
 ====Subsequent treatment====
 *Yahalom et al. 1993: CHOP versus [[#Observation|no further treatment]]
 *Kelsey et al. 1994: Chlorambucil versus [[#Observation|no further treatment]]
 *TROG 99.03: CVP or R-CVP versus [[#Observation|no further treatment]]
 ===References===
-# Yahalom J, Varsos G, Fuks Z, Myers J, Clarkson BD, Straus DJ. Adjuvant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy after radiation therapy in stage I low-grade and intermediate-grade non-Hodgkin lymphoma: results of a prospective randomized study. Cancer. 1993 Apr 1;71(7):2342-50. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19930401)71:7%3C2342::AID-CNCR2820710728%3E3.0.CO;2-I link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8453557 PubMed]
-# Kelsey SM, Newland AC, Hudson GV, Jelliffe AM. A British National Lymphoma Investigation randomised trial of single agent chlorambucil plus radiotherapy versus radiotherapy alone in low grade, localised non-Hodgkins lymphoma. Med Oncol. 1994;11(1):19-25. [https://link.springer.com/article/10.1007/BF02990087 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7921924 PubMed]
+#Yahalom J, Varsos G, Fuks Z, Myers J, Clarkson BD, Straus DJ. Adjuvant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy after radiation therapy in stage I low-grade and intermediate-grade non-Hodgkin lymphoma: results of a prospective randomized study. Cancer. 1993 Apr 1;71(7):2342-50. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19930401)71:7%3C2342::AID-CNCR2820710728%3E3.0.CO;2-I link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8453557 PubMed]
-# Lowry L, Smith P, Qian W, Falk S, Benstead K, Illidge T, Linch D, Robinson M, Jack A, Hoskin P. Reduced dose radiotherapy for local control in non-Hodgkin lymphoma: a randomised phase III trial. Radiother Oncol. 2011 Jul;100(1):86-92. Epub 2011 Jun 12. [https://www.thegreenjournal.com/article/S0167-8140(11)00205-2/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21664710 PubMed]
+#Kelsey SM, Newland AC, Hudson GV, Jelliffe AM. A British National Lymphoma Investigation randomised trial of single agent chlorambucil plus radiotherapy versus radiotherapy alone in low grade, localised non-Hodgkins lymphoma. Med Oncol. 1994;11(1):19-25. [https://link.springer.com/article/10.1007/BF02990087 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7921924 PubMed]
-# '''FORT:''' Hoskin PJ, Kirkwood AA, Popova B, Smith P, Robinson M, Gallop-Evans E, Coltart S, Illidge T, Madhavan K, Brammer C, Diez P, Jack A, Syndikus I. 4 Gy versus 24 Gy radiotherapy for patients with indolent lymphoma (FORT): a randomised phase 3 non-inferiority trial. Lancet Oncol. 2014 Apr;15(4):457-63. Epub 2014 Feb 24. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70036-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24572077 PubMed]
+#Lowry L, Smith P, Qian W, Falk S, Benstead K, Illidge T, Linch D, Robinson M, Jack A, Hoskin P. Reduced dose radiotherapy for local control in non-Hodgkin lymphoma: a randomised phase III trial. Radiother Oncol. 2011 Jul;100(1):86-92. Epub 2011 Jun 12. [https://www.thegreenjournal.com/article/S0167-8140(11)00205-2/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21664710 PubMed]
-# '''TROG 99.03:''' MacManus M, Fisher R, Roos D, O'Brien P, Macann A, Davis S, Tsang R, Christie D, McClure B, Joseph D, Jayamohan J, Seymour JF. Randomized trial of systemic therapy after involved-field radiotherapy in patients with early-stage follicular lymphoma: TROG 99.03. J Clin Oncol. 2018 Oct 10;36(29):2918-2925. Epub 2018 Jul 5. [https://ascopubs.org/doi/full/10.1200/JCO.2018.77.9892 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29975623 PubMed]
+#'''FORT:''' Hoskin PJ, Kirkwood AA, Popova B, Smith P, Robinson M, Gallop-Evans E, Coltart S, Illidge T, Madhavan K, Brammer C, Diez P, Jack A, Syndikus I. 4 Gy versus 24 Gy radiotherapy for patients with indolent lymphoma (FORT): a randomised phase 3 non-inferiority trial. Lancet Oncol. 2014 Apr;15(4):457-63. Epub 2014 Feb 24. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70036-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24572077 PubMed]
+#'''TROG 99.03:''' MacManus M, Fisher R, Roos D, O'Brien P, Macann A, Davis S, Tsang R, Christie D, McClure B, Joseph D, Jayamohan J, Seymour JF. Randomized trial of systemic therapy after involved-field radiotherapy in patients with early-stage follicular lymphoma: TROG 99.03. J Clin Oncol. 2018 Oct 10;36(29):2918-2925. Epub 2018 Jul 5. [https://ascopubs.org/doi/full/10.1200/JCO.2018.77.9892 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29975623 PubMed]
 =Early disease, adjuvant therapy=
@@ Line 108: / Line 119: @@
 ===Regimen===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://link.springer.com/article/10.1007/BF02990087 Kelsey et al. 1994]
@@ Line 131: / Line 142: @@
 ''No further treatment. Note that in TROG 99.03, patients enrolled after 2006 were randomized between this arm and R-CVP.''
 ====Preceding treatment====
 *[[#Radiation_therapy|Radiation therapy]]
 ===References===
-# Yahalom J, Varsos G, Fuks Z, Myers J, Clarkson BD, Straus DJ. Adjuvant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy after radiation therapy in stage I low-grade and intermediate-grade non-Hodgkin lymphoma: results of a prospective randomized study. Cancer. 1993 Apr 1;71(7):2342-50. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19930401)71:7%3C2342::AID-CNCR2820710728%3E3.0.CO;2-I link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8453557 PubMed]
-# Kelsey SM, Newland AC, Hudson GV, Jelliffe AM. A British National Lymphoma Investigation randomised trial of single agent chlorambucil plus radiotherapy versus radiotherapy alone in low grade, localised non-Hodgkins lymphoma. Med Oncol. 1994;11(1):19-25. [https://link.springer.com/article/10.1007/BF02990087 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7921924 PubMed]
+#Yahalom J, Varsos G, Fuks Z, Myers J, Clarkson BD, Straus DJ. Adjuvant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy after radiation therapy in stage I low-grade and intermediate-grade non-Hodgkin lymphoma: results of a prospective randomized study. Cancer. 1993 Apr 1;71(7):2342-50. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19930401)71:7%3C2342::AID-CNCR2820710728%3E3.0.CO;2-I link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8453557 PubMed]
-# '''TROG 99.03:''' MacManus M, Fisher R, Roos D, O'Brien P, Macann A, Davis S, Tsang R, Christie D, McClure B, Joseph D, Jayamohan J, Seymour JF. Randomized trial of systemic therapy after involved-field radiotherapy in patients with early-stage follicular lymphoma: TROG 99.03. J Clin Oncol. 2018 Oct 10;36(29):2918-2925. Epub 2018 Jul 5. [https://ascopubs.org/doi/full/10.1200/JCO.2018.77.9892 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29975623 PubMed]
+#Kelsey SM, Newland AC, Hudson GV, Jelliffe AM. A British National Lymphoma Investigation randomised trial of single agent chlorambucil plus radiotherapy versus radiotherapy alone in low grade, localised non-Hodgkins lymphoma. Med Oncol. 1994;11(1):19-25. [https://link.springer.com/article/10.1007/BF02990087 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7921924 PubMed]
+#'''TROG 99.03:''' MacManus M, Fisher R, Roos D, O'Brien P, Macann A, Davis S, Tsang R, Christie D, McClure B, Joseph D, Jayamohan J, Seymour JF. Randomized trial of systemic therapy after involved-field radiotherapy in patients with early-stage follicular lymphoma: TROG 99.03. J Clin Oncol. 2018 Oct 10;36(29):2918-2925. Epub 2018 Jul 5. [https://ascopubs.org/doi/full/10.1200/JCO.2018.77.9892 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29975623 PubMed]
 =Advanced disease, pre-phase=
@@ Line 145: / Line 159: @@
 ===Regimen {{#subobject:9134b2|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://jco.ascopubs.org/content/23/7/1500.long Hainsworth et al. 2005a]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |[http://www.sciencedirect.com/science/article/pii/S1557919011701962 Hainsworth et al. 2009]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 '''28-day course'''
 ====Subsequent treatment====
 *Hainsworth et al. 2005a: [[#R-CHOP|R-CHOP]] x 3 or [[#R-CVP|R-CVP]] x 3, then [[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab consolidation]]
 *Hainsworth et al. 2009: [[#R-CHOP|R-CHOP]] x 3, then [[#Ibritumomab_tiuxetan_monotherapy_3|Ibritumumab tiuxetan consolidation]]
 ===References===
-# Hainsworth JD, Litchy S, Morrissey LH, Andrews MB, Grimaldi M, McCarty M, Greco FA. Rituximab plus short-duration chemotherapy as first-line treatment for follicular non-Hodgkin's lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Mar 1;23(7):1500-6. Epub 2005 Jan 4. [http://jco.ascopubs.org/content/23/7/1500.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15632411 PubMed]
-# Hainsworth JD, Spigel DR, Markus TM, Shipley D, Thompson D, Rotman R, Dannaher C, Greco FA. Rituximab plus short-duration chemotherapy followed by yttrium-90 ibritumomab tiuxetan as first-line treatment for patients with follicular non-Hodgkin lymphoma: a phase II trial of the Sarah Cannon Oncology Research Consortium. Clin Lymphoma Myeloma. 2009 Jun;9(3):223-8. [http://www.sciencedirect.com/science/article/pii/S1557919011701962 link to SD article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19525191 PubMed]
+#Hainsworth JD, Litchy S, Morrissey LH, Andrews MB, Grimaldi M, McCarty M, Greco FA. Rituximab plus short-duration chemotherapy as first-line treatment for follicular non-Hodgkin's lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Mar 1;23(7):1500-6. Epub 2005 Jan 4. [http://jco.ascopubs.org/content/23/7/1500.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15632411 PubMed]
+#Hainsworth JD, Spigel DR, Markus TM, Shipley D, Thompson D, Rotman R, Dannaher C, Greco FA. Rituximab plus short-duration chemotherapy followed by yttrium-90 ibritumomab tiuxetan as first-line treatment for patients with follicular non-Hodgkin lymphoma: a phase II trial of the Sarah Cannon Oncology Research Consortium. Clin Lymphoma Myeloma. 2009 Jun;9(3):223-8. [http://www.sciencedirect.com/science/article/pii/S1557919011701962 link to SD article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19525191 PubMed]
 =Advanced disease, first-line therapy, randomized data=
@@ Line 176: / Line 194: @@
 ===Regimen {{#subobject:59f68f|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://www.nejm.org/doi/10.1056/NEJMoa1614598 Marcus et al. 2017 (GALLIUM)]
@@ Line 186: / Line 204: @@
 |[[Complex_multipart_regimens#GALLIUM|See link]]
 | style="background-color:#1a9850" |[[Complex_multipart_regimens#GALLIUM|See link]]
-| style="background-color:#1a9850" | style="background-color:#d73027" |[[Complex_multipart_regimens#GALLIUM|See link]]
+| style="background-color:#1a9850" |<nowiki>style="background-color:#d73027" |</nowiki>[[Complex_multipart_regimens#GALLIUM|See link]]
 |-
 |}
 ====Chemotherapy====
 *[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 *[[Obinutuzumab (Gazyva)]] as follows:
@@ Line 197: / Line 216: @@
 '''28-day cycle for 6 cycles'''
 ====Subsequent treatment====
 *[[#Obinutuzumab_monotherapy|Obinutuzumab maintenance]]
 ===References===
-# '''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://www.nejm.org/doi/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains verified protocol in appendix''' [https://www.ncbi.nlm.nih.gov/pubmed/28976863 PubMed]
-## '''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8960 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29856692 PubMed]
+#'''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://www.nejm.org/doi/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains verified protocol in appendix''' [https://www.ncbi.nlm.nih.gov/pubmed/28976863 PubMed]
+##'''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8960 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29856692 PubMed]
 ==BR {{#subobject:256065|Regimen=1}}==
@@ Line 211: / Line 233: @@
 ===Variant #1, 6 cycles {{#subobject:9e770b|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2961763-2/fulltext Rummel et al. 2013 (StiL NHL1)]
-|style="background-color:#1a9851"|Phase III (E-de-esc)
+| style="background-color:#1a9851" |Phase III (E-de-esc)
 |[[#R-CHOP|R-CHOP]]
-|style="background-color:#1a9850"|Superior PFS
+| style="background-color:#1a9850" |Superior PFS
 |
 |-
@@ Line 237: / Line 259: @@
 |}
 ====Chemotherapy====
 *[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 ====Supportive medications====
 *Antiemetics, antipyretics, and antibiotics according to local standard of care
 *Prophylactic use of [[:Category:Granulocyte colony-stimulating factors|G-CSF]] allowed according [http://jop.ascopubs.org/content/2/4/196.full ASCO guidelines] (2006)
@@ Line 246: / Line 270: @@
 '''28-day cycle for up to 6 cycles'''
 ====Subsequent treatment====
 *GALLIUM & RELEVANCE: [[#Rituximab_monotherapy.2C_extended_course|Rituximab maintenance]]
 ===Variant #2, 6 cycles with rituximab extension {{#subobject:503b17|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.bloodjournal.org/content/124/21/3052 Rummel et al. 2014 (MAINTAIN)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
 ====Chemotherapy====
 *[[Bendamustine]] as follows:
 **Cycles 1 to 6: 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
@@ Line 265: / Line 291: @@
 '''28-day cycle for 8 cycles'''
 ====Subsequent treatment====
 *[[#Rituximab_monotherapy.2C_extended_course|Rituximab maintenance]] x 2 y versus [[#Rituximab_monotherapy.2C_very_extended_course|rituximab maintenance]] x 4 y
 ===Variant #3, 8 cycles {{#subobject:9e89cz|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ Flinn et al. 2014 (BRIGHT)]
-|style="background-color:#1a9851"|Phase III (E-de-esc)
+| style="background-color:#1a9851" |Phase III (E-de-esc)
 |1. [[#R-CHOP|R-CHOP]]<br> 2. [[#R-CVP|R-CVP]]
-|style="background-color:#1a9850"|Superior PFS (*)
+| style="background-color:#1a9850" |Superior PFS (*)
 |-
 |}
 ''Efficacy in BRIGHT is based on the 2019 update. Patients in BRIGHT were required to be treatment-naive with a need for treatment per any of the following: B symptoms, large tumor mass (lymphomas with a diameter greater than 3 cm in 3 or more regions or diameter greater than 7 cm in 1 region), presence of lymphoma-related complications, or hyperviscosity syndrome attributed to monoclonal gammopathy.''
 ====Chemotherapy====
 *[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 ====Supportive medications====
 *Antiemetics, antipyretics, and antibiotics according to local standard of care
 *Prophylactic use of [[:Category:Granulocyte colony-stimulating factors|G-CSF]] allowed according [http://jop.ascopubs.org/content/2/4/196.full ASCO guidelines] (2006)
@@ Line 293: / Line 322: @@
 ===References===
 <!-- # '''Abstract:''' Mathias J. Rummel, Norbert Niederle, Georg Maschmeyer, Andre G. Banat, Ulrich von Gruenhagen, Christoph Losem, Dorothea Kofahl-Krause, Gerhard Heil, Manfred Welslau, Christina Balser, Ulrich Kaiser, Eckhart Weidmann, Heinz A. Duerk, Harald Ballo, Martina Stauch, Juergen Barth, Axel Hinke, Wolfram Brugger, Study Group Indolent Lymphomas (StiL). Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent and mantle cell lymphomas (MCL): Updated results from the StiL NHL1 study. 2012 ASCO Annual Meeting abstract 3. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview==abst_detail_view&confID==114&abstractID==95807 link to abstract] [http://www.ascopost.com/issues/july-1-2012/german-study-finds-bendamustine-improves-progression-free-survival-in-patients-with-non-hodgkin-lymphoma.aspx ASCO Post article] [http://www.asco.org/ASCOv2/MultiMedia/Virtual%20Meeting?&vmview==vm_session_presentations_view&confID==114&sessionID==4807 ASCO plenary session video] -->
-# '''StiL NHL1:''' Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Dürk H, Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W; Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013 Apr 6;381(9873):1203-10. Epub 2013 Feb 20. Erratum in: Lancet. 2013 Apr 6;381(9873):1184. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2961763-2/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23433739 PubMed]
-## '''Update: Abstract:''' Mathias J. Rummel, MD, Georg Maschmeyer, MD, Arnold Ganser, Andrea Heider, PhD, Ulrich von Grünhagen, MD, PhD5, Christoph Losem, Gerhard Heil, MD, Manfred Welslau, Christina Balser, MD, Ulrich Kaiser, MD, Eckhart Weidmann, Heinz Dürk, MD, Hans Peter Böck, Martina Beate Stauch, MD, Jürgen Barth, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Axel Hinke, PhD and Wolfram Brugger, MD. Bendamustine Plus Rituximab (B-R) Versus CHOP Plus Rituximab (CHOP-R) As First-Line Treatment in Patients with Indolent and Mantle Cell Lymphomas (MCL) – 7 Year Updated Results from the StiL NHL1 Study. Blood 2014 124:4407. [http://www.bloodjournal.org/content/124/21/4407 link to abstract]
+#'''StiL NHL1:''' Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Dürk H, Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W; Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013 Apr 6;381(9873):1203-10. Epub 2013 Feb 20. Erratum in: Lancet. 2013 Apr 6;381(9873):1184. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2961763-2/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23433739 PubMed]
-## '''Update: Abstract:''' Mathias J. Rummel, Georg Maschmeyer, Arnold Ganser, Andrea Heider, Ulrich von Gruenhagen, Christoph Losem, Gerhard Heil, Manfred Welslau, Christina Balser, Ulrich Kaiser, Eckhart Weidmann, Heinz Albert Dürk, Harald Ballo, Martina Stauch, Wolfgang Blau, Alexander Burchardt, Juergen Barth, Frank Kauff, and Wolfram Brugger. Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent lymphomas: Nine-year updated results from the StiL NHL1 study. Journal of Clinical Oncology 2017 35:15_suppl, 7501-7501 [https://ascopubs.org/doi/full/10.1200/JCO.2017.35.15_suppl.7501 link to abstract]
+##'''Update: Abstract:''' Mathias J. Rummel, MD, Georg Maschmeyer, MD, Arnold Ganser, Andrea Heider, PhD, Ulrich von Grünhagen, MD, PhD5, Christoph Losem, Gerhard Heil, MD, Manfred Welslau, Christina Balser, MD, Ulrich Kaiser, MD, Eckhart Weidmann, Heinz Dürk, MD, Hans Peter Böck, Martina Beate Stauch, MD, Jürgen Barth, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Axel Hinke, PhD and Wolfram Brugger, MD. Bendamustine Plus Rituximab (B-R) Versus CHOP Plus Rituximab (CHOP-R) As First-Line Treatment in Patients with Indolent and Mantle Cell Lymphomas (MCL) – 7 Year Updated Results from the StiL NHL1 Study. Blood 2014 124:4407. [http://www.bloodjournal.org/content/124/21/4407 link to abstract]
+##'''Update: Abstract:''' Mathias J. Rummel, Georg Maschmeyer, Arnold Ganser, Andrea Heider, Ulrich von Gruenhagen, Christoph Losem, Gerhard Heil, Manfred Welslau, Christina Balser, Ulrich Kaiser, Eckhart Weidmann, Heinz Albert Dürk, Harald Ballo, Martina Stauch, Wolfgang Blau, Alexander Burchardt, Juergen Barth, Frank Kauff, and Wolfram Brugger. Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent lymphomas: Nine-year updated results from the StiL NHL1 study. Journal of Clinical Oncology 2017 35:15_suppl, 7501-7501 [https://ascopubs.org/doi/full/10.1200/JCO.2017.35.15_suppl.7501 link to abstract]
 <!-- # '''Abstract:''' Ian Flinn et al. An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study. 2012 ASH Annual Meeting abstract 902. [https://ash.confex.com/ash/2012/webprogram/Paper51442.html link to abstract] -->
-# '''BRIGHT:''' Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. [http://bloodjournal.org/content/123/19/2944.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24591201 PubMed]
+#'''BRIGHT:''' Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. [http://bloodjournal.org/content/123/19/2944.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24591201 PubMed]
 <!-- ## '''Update: Abstract:''' Ian Flinn, Richard van der Jagt, Julie E. Chang, Peter Wood, Tim E. Hawkins, David MacDonald, Judith Trotman, David Simpson, Kathryn S. Kolibaba, Samar Issa, Doreen M. Hallman, Ling Chen, and John M. Burke. First-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP: Results of the BRIGHT 5-year follow-up study. Journal of Clinical Oncology 2017 35:15_suppl, 7500-7500 [https://ascopubs.org/doi/full/10.1200/JCO.2017.35.15_suppl.7500 link to abstract] -->
-## '''Update:''' Flinn IW, van der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, Simpson D, Kolibaba K, Issa S, Chang J, Trotman J, Hallman D, Chen L, Burke JM. First-line treatment of patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma with bendamustine plus rituximab versus R-CHOP or R-CVP: results of the BRIGHT 5-year follow-up study. J Clin Oncol. 2019 Apr 20;37(12):984-991. Epub 2019 Feb 27. [https://ascopubs.org/doi/full/10.1200/JCO.18.00605 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494265/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30811293 PubMed]
+##'''Update:''' Flinn IW, van der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, Simpson D, Kolibaba K, Issa S, Chang J, Trotman J, Hallman D, Chen L, Burke JM. First-line treatment of patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma with bendamustine plus rituximab versus R-CHOP or R-CVP: results of the BRIGHT 5-year follow-up study. J Clin Oncol. 2019 Apr 20;37(12):984-991. Epub 2019 Feb 27. [https://ascopubs.org/doi/full/10.1200/JCO.18.00605 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494265/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30811293 PubMed]
-# '''Abstract:''' Mathias J. Rummel, MD, Andreas Viardot, Richard Greil, MD, Bernd Hertenstein, MD, Christian Lerchenmüller, MD, Arnold Ganser, Manfred Reeb, MD, Ulrich Kaiser, MD, Christina Balser, MD, Georg Maschmeyer, MD, Heinz Dürk, MD, Georg Schliesser, MD, Tobias Gaska, MD, Jan Dürig, MD, Axel C. Matzdorff, MD, Rudolf Weide, MD, Axel Hinke, PhD, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Jürgen Barth and Wolfram Brugger, MD. Bendamustine Plus Rituximab Followed By Rituximab Maintenance for Patients with Untreated Advanced Follicular Lymphomas. Results from the StiL NHL 7-2008 Trial (MAINTAIN trial) (ClinicalTrials.gov Identifier: NCT00877214). Blood 2014 124:3052 [http://www.bloodjournal.org/content/124/21/3052 link to abstract]
+#'''Abstract:''' Mathias J. Rummel, MD, Andreas Viardot, Richard Greil, MD, Bernd Hertenstein, MD, Christian Lerchenmüller, MD, Arnold Ganser, Manfred Reeb, MD, Ulrich Kaiser, MD, Christina Balser, MD, Georg Maschmeyer, MD, Heinz Dürk, MD, Georg Schliesser, MD, Tobias Gaska, MD, Jan Dürig, MD, Axel C. Matzdorff, MD, Rudolf Weide, MD, Axel Hinke, PhD, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Jürgen Barth and Wolfram Brugger, MD. Bendamustine Plus Rituximab Followed By Rituximab Maintenance for Patients with Untreated Advanced Follicular Lymphomas. Results from the StiL NHL 7-2008 Trial (MAINTAIN trial) (ClinicalTrials.gov Identifier: NCT00877214). Blood 2014 124:3052 [http://www.bloodjournal.org/content/124/21/3052 link to abstract]
-# '''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://www.nejm.org/doi/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains verified protocol in appendix''' [https://www.ncbi.nlm.nih.gov/pubmed/28976863 PubMed]
+#'''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://www.nejm.org/doi/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains verified protocol in appendix''' [https://www.ncbi.nlm.nih.gov/pubmed/28976863 PubMed]
-## '''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8960 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29856692 PubMed]
+##'''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8960 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29856692 PubMed]
-# '''RELEVANCE:''' Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. [https://www.nejm.org/doi/full/10.1056/NEJMoa1805104 link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/30184451 PubMed]
+#'''RELEVANCE:''' Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. [https://www.nejm.org/doi/full/10.1056/NEJMoa1805104 link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/30184451 PubMed]
 ==Chlorambucil monotherapy {{#subobject:c89ee2|Regimen=1}}==
@@ Line 313: / Line 343: @@
 ===Regimen {{#subobject:6f7a21|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(03)14110-4/abstract Ardeshna et al. 2003]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Observation_2|Observation]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
 ''This is the comparator arm to the "watch and wait" strategy, and is not commonly used.''
 ====Chemotherapy====
 *[[Chlorambucil (Leukeran)]] 10 mg PO once per day
@@ Line 331: / Line 362: @@
 ===References===
-# Ardeshna KM, Smith P, Norton A, Hancock BW, Hoskin PJ, MacLennan KA, Marcus RE, Jelliffe A, Vaughan G, Hudson GV, Linch DC; British National Lymphoma Investigation. Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial. Lancet. 2003 Aug 16;362(9383):516-22. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(03)14110-4/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12932382 PubMed]
+#Ardeshna KM, Smith P, Norton A, Hancock BW, Hoskin PJ, MacLennan KA, Marcus RE, Jelliffe A, Vaughan G, Hudson GV, Linch DC; British National Lymphoma Investigation. Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial. Lancet. 2003 Aug 16;362(9383):516-22. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(03)14110-4/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12932382 PubMed]
 ==Cyclophosphamide monotherapy {{#subobject:4a0ab|Regimen=1}}==
@@ Line 341: / Line 373: @@
 ===Regimen {{#subobject:9b4e41|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/21/1/5.long Peterson et al. 2003 (CALGB 7951)]
-|style="background-color:#1a9851"|Phase III (E-de-esc)
+| style="background-color:#1a9851" |Phase III (E-de-esc)
 |[[Follicular_lymphoma_-_historical#CHOP-B|CHOP-B]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765852/ Smith et al. 2009 (CALGB 8691)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |Cyclophosphamide & Interferon alfa-2a
-|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 |-
 |}
 ''Note: this is an experimental arm that did not meet its primary endpoint; included here because it was eventually used to establish this regimen as a standard comparator.''
 ====Chemotherapy====
 *[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day
 **Dose modifications according to WBC and platelet count as listed in Table 1 of Peterson et al. 2003
@@ Line 365: / Line 398: @@
 ===References===
-# '''CALGB 7951:''' Peterson BA, Petroni GR, Frizzera G, Barcos M, Bloomfield CD, Nissen NI, Hurd DD, Henderson ES, Sartiano GP, Johnson JL, Holland JF, Gottlieb AJ. Prolonged single-agent versus combination chemotherapy in indolent follicular lymphomas: a study of the Cancer and Leukemia Group B. J Clin Oncol. 2003 Jan 1;21(1):5-15. [http://jco.ascopubs.org/content/21/1/5.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12506163 PubMed]
-# '''CALGB 8691:''' Smith SM, Johnson J, Cheson BD, Canellos G, Petroni G, Oken M, Duggan D, Hurd D, Gockerman JP, Parker B, Prchal J, Peterson BA; Cancer and Leukemia Group B; Eastern Cooperative Oncology Group. Recombinant interferon-alpha2b added to oral cyclophosphamide either as induction or maintenance in treatment-naive follicular lymphoma: final analysis of CALGB 8691. Leuk Lymphoma. 2009 Oct;50(10):1606-17. [https://www.tandfonline.com/doi/abs/10.1080/10428190903093807 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765852/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19626540 PubMed]
+#'''CALGB 7951:''' Peterson BA, Petroni GR, Frizzera G, Barcos M, Bloomfield CD, Nissen NI, Hurd DD, Henderson ES, Sartiano GP, Johnson JL, Holland JF, Gottlieb AJ. Prolonged single-agent versus combination chemotherapy in indolent follicular lymphomas: a study of the Cancer and Leukemia Group B. J Clin Oncol. 2003 Jan 1;21(1):5-15. [http://jco.ascopubs.org/content/21/1/5.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12506163 PubMed]
+#'''CALGB 8691:''' Smith SM, Johnson J, Cheson BD, Canellos G, Petroni G, Oken M, Duggan D, Hurd D, Gockerman JP, Parker B, Prchal J, Peterson BA; Cancer and Leukemia Group B; Eastern Cooperative Oncology Group. Recombinant interferon-alpha2b added to oral cyclophosphamide either as induction or maintenance in treatment-naive follicular lymphoma: final analysis of CALGB 8691. Leuk Lymphoma. 2009 Oct;50(10):1606-17. [https://www.tandfonline.com/doi/abs/10.1080/10428190903093807 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765852/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19626540 PubMed]
 ==G-CVP {{#subobject:3a87a2|Regimen=1}}==
@@ Line 376: / Line 410: @@
 ===Regimen {{#subobject:9a74a2|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://www.nejm.org/doi/10.1056/NEJMoa1614598 Marcus et al. 2017 (GALLIUM)]
@@ Line 386: / Line 420: @@
 |[[Complex_multipart_regimens#GALLIUM|See link]]
 | style="background-color:#1a9850" |[[Complex_multipart_regimens#GALLIUM|See link]]
-| style="background-color:#1a9850" | style="background-color:#d73027" |[[Complex_multipart_regimens#GALLIUM|See link]]
+| style="background-color:#1a9850" |<nowiki>style="background-color:#d73027" |</nowiki>[[Complex_multipart_regimens#GALLIUM|See link]]
 |-
 |}
 ''Note: Patients received obinutuzumab only in cycles 7 & 8.''
 ====Chemotherapy====
 *[[Obinutuzumab (Gazyva)]] as follows:
 **Cycle 1: 1000 mg IV once per day on days 1, 8, 15
@@ Line 400: / Line 435: @@
 '''21-day cycle for 8 cycles'''
 ====Subsequent treatment====
 *[[#Obinutuzumab_monotherapy|Obinutuzumab maintenance]]
 ===References===
-# '''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://www.nejm.org/doi/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains verified protocol in appendix''' [https://www.ncbi.nlm.nih.gov/pubmed/28976863 PubMed]
-## '''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8960 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29856692 PubMed]
+#'''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://www.nejm.org/doi/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains verified protocol in appendix''' [https://www.ncbi.nlm.nih.gov/pubmed/28976863 PubMed]
+##'''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8960 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29856692 PubMed]
 ==G-CHOP {{#subobject:65eebc|Regimen=1}}==
@@ Line 413: / Line 451: @@
 ===Regimen {{#subobject:b8573d|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://www.nejm.org/doi/10.1056/NEJMoa1614598 Marcus et al. 2017 (GALLIUM)]
@@ Line 423: / Line 461: @@
 |[[Complex_multipart_regimens#GALLIUM|See link]]
 | style="background-color:#1a9850" |[[Complex_multipart_regimens#GALLIUM|See link]]
-| style="background-color:#1a9850" | style="background-color:#d73027" |[[Complex_multipart_regimens#GALLIUM|See link]]
+| style="background-color:#1a9850" |<nowiki>style="background-color:#d73027" |</nowiki>[[Complex_multipart_regimens#GALLIUM|See link]]
 |-
 |}
 ''Note: Patients received obinutuzumab only in cycles 7 & 8.''
 ====Chemotherapy====
 *[[Obinutuzumab (Gazyva)]] as follows:
 **Cycle 1: 1000 mg IV once per day on days 1, 8, 15
@@ Line 438: / Line 477: @@
 '''21-day cycle for 8 cycles'''
 ====Subsequent treatment====
 *[[#Obinutuzumab_monotherapy|Obinutuzumab maintenance]]
 ===References===
-# '''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://www.nejm.org/doi/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains verified protocol in appendix''' [https://www.ncbi.nlm.nih.gov/pubmed/28976863 PubMed]
-## '''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8960 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29856692 PubMed]
+#'''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://www.nejm.org/doi/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains verified protocol in appendix''' [https://www.ncbi.nlm.nih.gov/pubmed/28976863 PubMed]
+##'''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8960 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29856692 PubMed]
 ==Lenalidomide & Rituximab {{#subobject:986935|Regimen=1}}==
@@ Line 451: / Line 493: @@
 ===Variant #1 {{#subobject:88de66|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.bloodjournal.org/content/134/4/353.long Zucca et al. 2019 (SAKK 35/10)]
-|style="background-color:#1a9851"|Randomized Phase II (E-esc)
+| style="background-color:#1a9851" |Randomized Phase II (E-esc)
 |[[#Rituximab_monotherapy_2|Rituximab]]
 | style="background-color:#d9ef8b" |Might have superior CR/CRu rate
@@ Line 463: / Line 505: @@
 |}
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 15 mg PO once per day, starting 14 days prior to first rituximab infusion and continuing until 14 days past last rituximab infusion
 *[[Rituximab (Rituxan)]] as follows:
@@ Line 471: / Line 514: @@
 ===Variant #2 {{#subobject:d69b11|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70455-3/fulltext Fowler et al. 2014]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 486: / Line 530: @@
 ===Variant #3 {{#subobject:2a6690|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://academic.oup.com/annonc/article/28/11/2806/4098872 Martin et al. 2017 (CALGB 50803)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 *[[Rituximab (Rituxan)]] as follows:
@@ Line 503: / Line 548: @@
 ===Variant #4 {{#subobject:8fb47f|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://www.nejm.org/doi/full/10.1056/NEJMoa1805104 Morschhauser et al. 2018 (RELEVANCE)]
@@ Line 517: / Line 562: @@
 |}
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 2 to 22
 *[[Rituximab (Rituxan)]] as follows:
@@ Line 524: / Line 570: @@
 '''28-day cycle for 6 cycles'''
 ====Subsequent treatment====
 *Responders: [[#Lenalidomide_.26_Rituximab_2|Lenalidomide & Rituximab maintenance]]
@@ Line 530: / Line 577: @@
 # '''Abstract:''' N. H. Fowler, P. McLaughlin, F. B. Hagemeister, L. W. Kwak, M. A. Fanale, S. S. Neelapu, L. Fayad, R. Z. Orlowski, M. Wang, F. Samaniego. Complete response rates with lenalidomide plus rituximab for untreated indolent B-cell non-Hodgkin's lymphoma. J Clin Oncol 28:15s, 2010 (suppl; abstr 8036). 2010 ASCO Annual Meeting abstract 8036. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview==abst_detail_view&confID==74&abstractID==53803 link to abstract]
 # '''Abstract:''' Nathan H Fowler, MD, Sattva S. Neelapu, MD, Fredrick B Hagemeister, MD, Peter McLaughlin, MD, Larry W. Kwak, MD, PhD, Jorge E Romaguera, MD, Michelle A. Fanale, MD, Luis E Fayad, MD, Robert Z. Orlowski, M.D., Ph.D., Michael Wang, M.D., Francesco Turturro, MD, Yasuhiro Oki, MD, Linda Catherine Lacerte, RN and Felipe Samaniego, MD, MPH. Lenalidomide and Rituximab for Untreated Indolent Lymphoma: Final Results of a Phase II Study. 2012 ASH Annual Meeting abstract 901. [http://abstracts.hematologylibrary.org/cgi/content/abstract/120/21/901 link to abstract] -->
-# Fowler NH, Davis RE, Rawal S, Nastoupil L, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale MA, Fayad LE, Westin JR, Shah J, Orlowski RZ, Wang M, Turturro F, Oki Y, Claret LC, Feng L, Baladandayuthapani V, Muzzafar T, Tsai KY, Samaniego F, Neelapu SS. Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial. Lancet Oncol. 2014 Nov;15(12):1311-8. Epub 2014 Oct 15. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70455-3/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370362/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25439689 PubMed]
+#Fowler NH, Davis RE, Rawal S, Nastoupil L, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale MA, Fayad LE, Westin JR, Shah J, Orlowski RZ, Wang M, Turturro F, Oki Y, Claret LC, Feng L, Baladandayuthapani V, Muzzafar T, Tsai KY, Samaniego F, Neelapu SS. Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial. Lancet Oncol. 2014 Nov;15(12):1311-8. Epub 2014 Oct 15. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70455-3/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370362/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25439689 PubMed]
 <!-- # '''Abstract:''' Eva Kimby, Giovanni Martinelli, Bjorn Ostenstad, Ulrich JM Mey, Daniel Rauch, Björn E Wahlin, MD, PhD, Felicitas Hitz, MD, Micaela Hernberg, Ann-Sofie Johansson, Peter de Nully Brown, Hans Hagberg, Andrés J.M. Ferreri1, Andreas Lohri, Urban Novak, Thilo Zander, Hanne Bersvendsen, Mario Bargetzi, Walter Mingrone, Fatime Krasniqi, Stephan Dirnhofer, Hanne Hawle, MD, Simona Berardi, Steffi Demmel, Stephanie Rondeau and Emanuele Zucca, MD. Rituximab Plus Lenalidomide Improves the Complete Remission Rate in Comparison with Rituximab Monotherapy in Untreated Follicular Lymphoma Patients in Need of Therapy. Primary Endpoint Analysis of the Randomized Phase-2 Trial SAKK 35/10. ASH Annual Meeting 2014 Abstract 799 [http://www.bloodjournal.org/content/124/21/799 link to abstract] -->
-# '''SAKK 35/10:''' Zucca E, Rondeau S, Vanazzi A, Østenstad B, Mey UJM, Rauch D, Wahlin BE, Hitz F, Hernberg M, Johansson AS, de Nully Brown P, Hagberg H, Ferreri AJM, Lohri A, Novak U, Zander T, Bersvendsen H, Bargetzi M, Mingrone W, Krasniqi F, Dirnhofer S, Hayoz S, Hawle H, Vilei SB, Ghielmini M, Kimby E; Swiss Group for Clinical Cancer Research and the Nordic Lymphoma Group. Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy. Blood. 2019 Jul 25;134(4):353-362. Epub 2019 May 17. [http://www.bloodjournal.org/content/134/4/353.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/31101627 PubMed]
+#'''SAKK 35/10:''' Zucca E, Rondeau S, Vanazzi A, Østenstad B, Mey UJM, Rauch D, Wahlin BE, Hitz F, Hernberg M, Johansson AS, de Nully Brown P, Hagberg H, Ferreri AJM, Lohri A, Novak U, Zander T, Bersvendsen H, Bargetzi M, Mingrone W, Krasniqi F, Dirnhofer S, Hayoz S, Hawle H, Vilei SB, Ghielmini M, Kimby E; Swiss Group for Clinical Cancer Research and the Nordic Lymphoma Group. Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy. Blood. 2019 Jul 25;134(4):353-362. Epub 2019 May 17. [http://www.bloodjournal.org/content/134/4/353.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/31101627 PubMed]
 <!-- # '''Abstract:''' Peter Martin, Sin-Ho Jung, Jeffrey L. Johnson, Brandy Pitcher, Rebecca L. Elstrom, Nancy Bartlett, Kristie A. Blum, Kristy L. Richards... John Leonard, Bruce D. Cheson. CALGB 50803 (Alliance): A phase II trial of lenalidomide plus rituximab in patients with previously untreated follicular lymphoma. Journal of Clinical Oncology 32, no. 15_suppl (May 2014) 8521-8521. [https://ascopubs.org/doi/full/10.1200/jco.2014.32.15_suppl.8521 link to abstract] -->
-# '''CALGB 50803:''' Martin P, Jung SH, Pitcher B, Bartlett NL, Blum KA, Shea T, Hsi ED, Ruan J, Smith SE, Leonard JP, Cheson BD. A phase II trial of lenalidomide plus rituximab in previously untreated follicular non-Hodgkin's lymphoma (NHL): CALGB 50803 (Alliance). Ann Oncol. 2017 Nov 1;28(11):2806-2812. [https://academic.oup.com/annonc/article/28/11/2806/4098872 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28945884 PubMed]
+#'''CALGB 50803:''' Martin P, Jung SH, Pitcher B, Bartlett NL, Blum KA, Shea T, Hsi ED, Ruan J, Smith SE, Leonard JP, Cheson BD. A phase II trial of lenalidomide plus rituximab in previously untreated follicular non-Hodgkin's lymphoma (NHL): CALGB 50803 (Alliance). Ann Oncol. 2017 Nov 1;28(11):2806-2812. [https://academic.oup.com/annonc/article/28/11/2806/4098872 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28945884 PubMed]
-# '''RELEVANCE:''' Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. [https://www.nejm.org/doi/full/10.1056/NEJMoa1805104 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30184451 PubMed]
+#'''RELEVANCE:''' Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. [https://www.nejm.org/doi/full/10.1056/NEJMoa1805104 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30184451 PubMed]
 ==Observation==
@@ Line 545: / Line 593: @@
 ===Regimen===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.nejm.org/doi/full/10.1056/NEJM198412063112303 Horning & Rosenberg 1984]
-|style="background-color:#91cf61"|Non-randomized
+| style="background-color:#91cf61" |Non-randomized
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://www.ncbi.nlm.nih.gov/pubmed/2456618 Young et al. 1988]
-|style="background-color:#1a9851"|Phase III (E-de-esc)
+| style="background-color:#1a9851" |Phase III (E-de-esc)
 |[[Follicular_lymphoma_-_historical#ProMACE-MOPP|ProMACE-MOPP, then TNI]]
 |
 |-
 |[http://jco.ascopubs.org/content/15/3/1110.long Brice et al. 1997]
-|style="background-color:#1a9851"|Phase III (E-de-esc)
+| style="background-color:#1a9851" |Phase III (E-de-esc)
 |1. Interferon alfa<br> 2. Prednimustine
-|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(03)14110-4/abstract Ardeshna et al. 2003]
-|style="background-color:#1a9851"|Phase III (E-de-esc)
+| style="background-color:#1a9851" |Phase III (E-de-esc)
 |[[#Chlorambucil_monotherapy|Chlorambucil]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|rowspan=2|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70027-0/abstract Ardeshna et al. 2014 (CRUK-2004-001621-16)]
+| rowspan="2" |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70027-0/abstract Ardeshna et al. 2014 (CRUK-2004-001621-16)]
-|rowspan=2 style="background-color:#1a9851"|Phase III (C)
+| rowspan="2" style="background-color:#1a9851" |Phase III (C)
 |1. [[#Rituximab_monotherapy_2|Rituximab induction]]
-|style="background-color:#d73027"|Inferior TTNT
+| style="background-color:#d73027" |Inferior TTNT
 |-
 |2. [[#Rituximab_monotherapy_2|Rituximab induction]], then [[#Rituximab_monotherapy.2C_extended_course|Rituximab maintenance]]
-|style="background-color:#d73027"|Inferior TTNT
+| style="background-color:#d73027" |Inferior TTNT
 |-
 |}
@@ Line 583: / Line 631: @@
 ===References===
-# Horning SJ, Rosenberg SA. The natural history of initially untreated low-grade non-Hodgkin's lymphomas. N Engl J Med. 1984 Dec 6;311(23):1471-5. [https://www.nejm.org/doi/full/10.1056/NEJM198412063112303 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6548796 PubMed]
-# Young RC, Longo DL, Glatstein E, Ihde DC, Jaffe ES, DeVita VT Jr. The treatment of indolent lymphomas: watchful waiting v aggressive combined modality treatment. Semin Hematol. 1988 Apr;25(2 Suppl 2):11-6. [https://www.ncbi.nlm.nih.gov/pubmed/2456618 PubMed]
+#Horning SJ, Rosenberg SA. The natural history of initially untreated low-grade non-Hodgkin's lymphomas. N Engl J Med. 1984 Dec 6;311(23):1471-5. [https://www.nejm.org/doi/full/10.1056/NEJM198412063112303 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6548796 PubMed]
-# Brice P, Bastion Y, Lepage E, Brousse N, Haïoun C, Moreau P, Straetmans N, Tilly H, Tabah I, Solal-Céligny P. Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d'Etude des Lymphomes Folliculaires; Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 1997 Mar;15(3):1110-7. [http://jco.ascopubs.org/content/15/3/1110.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9060552 PubMed]
+#Young RC, Longo DL, Glatstein E, Ihde DC, Jaffe ES, DeVita VT Jr. The treatment of indolent lymphomas: watchful waiting v aggressive combined modality treatment. Semin Hematol. 1988 Apr;25(2 Suppl 2):11-6. [https://www.ncbi.nlm.nih.gov/pubmed/2456618 PubMed]
-# Ardeshna KM, Smith P, Norton A, Hancock BW, Hoskin PJ, MacLennan KA, Marcus RE, Jelliffe A, Vaughan G, Hudson GV, Linch DC; British National Lymphoma Investigation. Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial. Lancet. 2003 Aug 16;362(9383):516-22. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(03)14110-4/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12932382 PubMed]
+#Brice P, Bastion Y, Lepage E, Brousse N, Haïoun C, Moreau P, Straetmans N, Tilly H, Tabah I, Solal-Céligny P. Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d'Etude des Lymphomes Folliculaires; Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 1997 Mar;15(3):1110-7. [http://jco.ascopubs.org/content/15/3/1110.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9060552 PubMed]
-# '''CRUK-2004-001621-16:''' Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P, Warden J, Stevens L, Pocock CF, Miall F, Cunningham D, Davies J, Jack A, Stephens R, Walewski J, Ferhanoglu B, Bradstock K, Linch DC. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol. 2014 Apr;15(4):424-35. Epub 2014 Mar 4. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70027-0/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24602760 PubMed]
+#Ardeshna KM, Smith P, Norton A, Hancock BW, Hoskin PJ, MacLennan KA, Marcus RE, Jelliffe A, Vaughan G, Hudson GV, Linch DC; British National Lymphoma Investigation. Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial. Lancet. 2003 Aug 16;362(9383):516-22. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(03)14110-4/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12932382 PubMed]
+#'''CRUK-2004-001621-16:''' Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P, Warden J, Stevens L, Pocock CF, Miall F, Cunningham D, Davies J, Jack A, Stephens R, Walewski J, Ferhanoglu B, Bradstock K, Linch DC. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol. 2014 Apr;15(4):424-35. Epub 2014 Mar 4. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70027-0/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24602760 PubMed]
 ==R-CHOP {{#subobject:f05383|Regimen=1}}==
@@ Line 597: / Line 646: @@
 ===Variant #1, 3 cycles with prednisone 100 mg {{#subobject:30c25c|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://jco.ascopubs.org/content/23/7/1500.long Hainsworth et al. 2005a]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |[http://www.sciencedirect.com/science/article/pii/S1557919011701962 Hainsworth et al. 2009]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 ====Preceding treatment====
 *[[#Rituximab_monotherapy|Rituximab pre-phase]] x 4
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 619: / Line 671: @@
 '''21-day cycle for 3 cycles'''
 ====Subsequent treatment====
 *Hainsworth et al. 2005a: [[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab consolidation]]
 *Hainsworth et al. 2009: [[#Ibritumomab_tiuxetan_monotherapy_3|Ibritumumab tiuxetan consolidation]], in 4 weeks
@@ Line 624: / Line 677: @@
 ===Variant #2, 3 cycles with prednisone 100 mg/m<sup>2</sup> {{#subobject:aae4db|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://clincancerres.aacrjournals.org/content/14/21/7088.long Jacobs et al. 2008]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. R-CHOP given as per standard ECOG dosing, except that rituximab is given on day 1 of each cycle:''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 640: / Line 694: @@
 ====Supportive medications====
 *[[Filgrastim (Neupogen)]] "recommended according to guidelines"
 '''21-day cycle for 3 cycles'''
 ====Subsequent treatment====
 *[[#Ibritumomab_tiuxetan_monotherapy_3|Ibritumumab tiuxetan consolidation]]
 ===Variant #3, prednisone 100 mg {{#subobject:13e254|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2962175-7/fulltext Salles et al. 2010 (PRIMA)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ Flinn et al. 2014 (BRIGHT)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#BR|BR]]
-|style="background-color:#eeee01"|Seems to have non-inferior CR rate
+| style="background-color:#eeee01" |Seems to have non-inferior CR rate
 |
 |-
@@ Line 681: / Line 737: @@
 ''In PRIMA, initial therapy was investigator's choice. Patients in BRIGHT were required to be treatment-naive with a need for treatment per any of the following: B symptoms, large tumor mass (lymphomas with a diameter greater than 3 cm in 3 or more regions or diameter greater than 7 cm in 1 region), presence of lymphoma-related complications, or hyperviscosity syndrome attributed to monoclonal gammopathy. Patients in GALLIUM & RELEVANCE received rituximab only in cycles 7 & 8.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 688: / Line 745: @@
 ====Supportive medications====
 *Antiemetics, antipyretics, and antibiotics per local standard of care
 *[[:Category:Granulocyte colony-stimulating factors|G-CSF]] "according to the [http://jco.ascopubs.org/content/18/20/3558.full American Society of Clinical Oncology guidelines]"
@@ Line 693: / Line 751: @@
 '''21-day cycle for 6 to 8 cycles (see note)'''
 ====Subsequent treatment====
 *PRIMA, responders (PR or CR): [[#Rituximab_monotherapy.2C_extended_course|Maintenance rituximab]] versus [[#Observation_3|no further treatment]]
 *GALLIUM & RELEVANCE: [[#Rituximab_monotherapy.2C_extended_course|Maintenance rituximab]]
@@ Line 698: / Line 757: @@
 ===Variant #4, prednisone 100 mg/m<sup>2</sup> {{#subobject:74f424|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[http://www.bloodjournal.org/content/106/12/3725.long Hiddemann et al. 2005 (GLSG '00)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[Follicular_lymphoma_-_historical#CHOP|CHOP]]
-|style="background-color:#91cf60"|Seems to have superior OS
+| style="background-color:#91cf60" |Seems to have superior OS
-|style="background-color:#d73027"|Increased toxicity
+| style="background-color:#d73027" |Increased toxicity
 |-
-|rowspan=2|[http://jco.ascopubs.org/content/31/12/1506.long Federico et al. 2013 (FOLL05)]
+| rowspan="2" |[http://jco.ascopubs.org/content/31/12/1506.long Federico et al. 2013 (FOLL05)]
-|rowspan=2 style="background-color:#1a9851"|Phase III (E-esc)
+| rowspan="2" style="background-color:#1a9851" |Phase III (E-esc)
 |1. [[#R-CVP|R-CVP]]
-|style="background-color:#91cf60"|Seems to have superior PFS
+| style="background-color:#91cf60" |Seems to have superior PFS
 |
 |-
 |2. [[#R-FM|R-FM]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of TTF
+| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
 |
 |-
@@ Line 723: / Line 782: @@
 ''In FOLL05, PFS was superior to R-CVP but equivalent to R-FM; risk/benefit ratio was better than R-FM. Patients in FOLL05 received a total of 8 doses of rituximab, regardless of the number of CHOP cycles.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on either day 1 or day -1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 733: / Line 793: @@
 ===Variant #5, variant rituximab schedule {{#subobject:caca45|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/17/1/268.full Czuczman et al. 1999]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732010/ Press et al. 2012 (SWOG S0016)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
-|CHOP.2C_then_131Iodine-Tositumomab_.28Bexxar.29|CHOP, then <sup>131</sup>Iodine-Tositumomab
+| CHOP.2C_then_131Iodine-Tositumomab_.28Bexxar.29 |CHOP, then <sup>131</sup>Iodine-Tositumomab
 | style="background-color:#d73027" |Inferior PFS (*)
 |-
@@ Line 751: / Line 811: @@
 ''In SWOG S0016, this regimen was intended for patients greater than 18 years with untreated bulky stage II or stage III-IV FL (all grades) expressing CD20. Reported efficacy for SWOG S0016 is based on the 2018 update.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows:
 **Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days -7 & -2
@@ Line 764: / Line 825: @@
 ===Variant #6, 4 doses of rituximab {{#subobject:7f4db5|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/29/30/3990.long Watanabe et al. 2011 (JCOG 0203)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |R-CHOP-14
-|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 |-
 |}
 ''This regimen was intended for patients with previously untreated stage III to IV indolent B-cell NHL, including FL grade 3B.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows:
 **Cycles 1, 2, 4, 6: 375 mg/m<sup>2</sup> IV once on day -2
@@ Line 785: / Line 847: @@
 ====Supportive medications====
 *[[:Category:Granulocyte colony-stimulating factors|G-CSF]] "according to the [2000] [http://jco.ascopubs.org/content/18/20/3558.full American Society of Clinical Oncology guidelines]," i.e., generally no routine use except for patients at high risk (>40%) for febrile neutropenia due to special circumstances
@@ Line 790: / Line 853: @@
 ===References===
-# Czuczman MS, Grillo-López AJ, White CA, Saleh M, Gordon L, LoBuglio AF, Jonas C, Klippenstein D, Dallaire B, Varns C. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol. 1999 Jan;17(1):268-76. [http://jco.ascopubs.org/content/17/1/268.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10458242 PubMed]
-## '''Update:''' Czuczman MS, Weaver R, Alkuzweny B, Berlfein J, Grillo-López AJ. Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin's lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol. 2004 Dec 1;22(23):4711 to 6. Epub 2004 Oct 13. [http://jco.ascopubs.org/content/22/23/4711.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15483015 PubMed]
+#Czuczman MS, Grillo-López AJ, White CA, Saleh M, Gordon L, LoBuglio AF, Jonas C, Klippenstein D, Dallaire B, Varns C. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol. 1999 Jan;17(1):268-76. [http://jco.ascopubs.org/content/17/1/268.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10458242 PubMed]
-# Hainsworth JD, Litchy S, Morrissey LH, Andrews MB, Grimaldi M, McCarty M, Greco FA. Rituximab plus short-duration chemotherapy as first-line treatment for follicular non-Hodgkin's lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Mar 1;23(7):1500-6. Epub 2005 Jan 4. [http://jco.ascopubs.org/content/23/7/1500.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15632411 PubMed]
+##'''Update:''' Czuczman MS, Weaver R, Alkuzweny B, Berlfein J, Grillo-López AJ. Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin's lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol. 2004 Dec 1;22(23):4711 to 6. Epub 2004 Oct 13. [http://jco.ascopubs.org/content/22/23/4711.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15483015 PubMed]
-# '''GLSG '00:''' Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, Reiser M, Metzner B, Harder H, Hegewisch-Becker S, Fischer T, Kropff M, Reis HE, Freund M, Wörmann B, Fuchs R, Planker M, Schimke J, Eimermacher H, Trümper L, Aldaoud A, Parwaresch R, Unterhalt M. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005 Dec 1;106(12):3725-32. Epub 2005 Aug 25. [http://www.bloodjournal.org/content/106/12/3725.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16123223 PubMed]
+#Hainsworth JD, Litchy S, Morrissey LH, Andrews MB, Grimaldi M, McCarty M, Greco FA. Rituximab plus short-duration chemotherapy as first-line treatment for follicular non-Hodgkin's lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Mar 1;23(7):1500-6. Epub 2005 Jan 4. [http://jco.ascopubs.org/content/23/7/1500.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15632411 PubMed]
-# Jacobs SA, Swerdlow SH, Kant J, Foon KA, Jankowitz R, Land SR, DeMonaco N, Joyce J, Osborn JL, Evans TL, Schaefer PM, Luong TM. Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Clin Cancer Res. 2008 Nov 1;14(21):7088-94. [http://clincancerres.aacrjournals.org/content/14/21/7088.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18981007 PubMed]
+#'''GLSG '00:''' Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, Reiser M, Metzner B, Harder H, Hegewisch-Becker S, Fischer T, Kropff M, Reis HE, Freund M, Wörmann B, Fuchs R, Planker M, Schimke J, Eimermacher H, Trümper L, Aldaoud A, Parwaresch R, Unterhalt M. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005 Dec 1;106(12):3725-32. Epub 2005 Aug 25. [http://www.bloodjournal.org/content/106/12/3725.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16123223 PubMed]
-# Hainsworth JD, Spigel DR, Markus TM, Shipley D, Thompson D, Rotman R, Dannaher C, Greco FA. Rituximab plus short-duration chemotherapy followed by yttrium-90 ibritumomab tiuxetan as first-line treatment for patients with follicular non-Hodgkin lymphoma: a phase II trial of the Sarah Cannon Oncology Research Consortium. Clin Lymphoma Myeloma. 2009 Jun;9(3):223-8. [http://www.sciencedirect.com/science/article/pii/S1557919011701962 link to SD article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19525191 PubMed]
+#Jacobs SA, Swerdlow SH, Kant J, Foon KA, Jankowitz R, Land SR, DeMonaco N, Joyce J, Osborn JL, Evans TL, Schaefer PM, Luong TM. Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Clin Cancer Res. 2008 Nov 1;14(21):7088-94. [http://clincancerres.aacrjournals.org/content/14/21/7088.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18981007 PubMed]
-# '''PRIMA:''' Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2962175-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21176949 PubMed]
+#Hainsworth JD, Spigel DR, Markus TM, Shipley D, Thompson D, Rotman R, Dannaher C, Greco FA. Rituximab plus short-duration chemotherapy followed by yttrium-90 ibritumomab tiuxetan as first-line treatment for patients with follicular non-Hodgkin lymphoma: a phase II trial of the Sarah Cannon Oncology Research Consortium. Clin Lymphoma Myeloma. 2009 Jun;9(3):223-8. [http://www.sciencedirect.com/science/article/pii/S1557919011701962 link to SD article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19525191 PubMed]
-## '''QoL Analysis:''' Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. [http://www.maneyonline.com/doi/full/10.1179/1607845414Y.0000000179 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25029908 PubMed]
+#'''PRIMA:''' Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2962175-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21176949 PubMed]
-## '''Update:''' Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. [https://ascopubs.org/doi/full/10.1200/JCO.19.01073 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823890/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/31339826 PubMed]
+##'''QoL Analysis:''' Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. [http://www.maneyonline.com/doi/full/10.1179/1607845414Y.0000000179 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25029908 PubMed]
-# '''JCOG 0203:''' Watanabe T, Tobinai K, Shibata T, Tsukasaki K, Morishima Y, Maseki N, Kinoshita T, Suzuki T, Yamaguchi M, Ando K, Ogura M, Taniwaki M, Uike N, Takeuchi K, Nawano S, Terauchi T, Hotta T. Phase II/III study of R-CHOP-21 versus R-CHOP-14 for untreated indolent B-cell non-Hodgkin's lymphoma: JCOG 0203 trial. J Clin Oncol. 2011 Oct 20;29(30):3990-8. Epub 2011 Sep 19. [http://jco.ascopubs.org/content/29/30/3990.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21931035 PubMed]
+##'''Update:''' Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. [https://ascopubs.org/doi/full/10.1200/JCO.19.01073 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823890/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/31339826 PubMed]
-## '''Update:''' Watanabe T, Tobinai K, Wakabayashi M, Morishima Y, Kobayashi H, Kinoshita T, Suzuki T, Yamaguchi M, Ando K, Ogura M, Taniwaki M, Uike N, Yoshino T, Nawano S, Terauchi T, Hotta T, Nagai H, Tsukasaki K; JCOG0203 Collaborators. Outcomes after R-CHOP in patients with newly diagnosed advanced follicular lymphoma: a 10-year follow-up analysis of the JCOG0203 trial. Lancet Haematol. 2018 Nov;5(11):e520-e531. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(18)30155-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30389034 PubMed]
+#'''JCOG 0203:''' Watanabe T, Tobinai K, Shibata T, Tsukasaki K, Morishima Y, Maseki N, Kinoshita T, Suzuki T, Yamaguchi M, Ando K, Ogura M, Taniwaki M, Uike N, Takeuchi K, Nawano S, Terauchi T, Hotta T. Phase II/III study of R-CHOP-21 versus R-CHOP-14 for untreated indolent B-cell non-Hodgkin's lymphoma: JCOG 0203 trial. J Clin Oncol. 2011 Oct 20;29(30):3990-8. Epub 2011 Sep 19. [http://jco.ascopubs.org/content/29/30/3990.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21931035 PubMed]
+##'''Update:''' Watanabe T, Tobinai K, Wakabayashi M, Morishima Y, Kobayashi H, Kinoshita T, Suzuki T, Yamaguchi M, Ando K, Ogura M, Taniwaki M, Uike N, Yoshino T, Nawano S, Terauchi T, Hotta T, Nagai H, Tsukasaki K; JCOG0203 Collaborators. Outcomes after R-CHOP in patients with newly diagnosed advanced follicular lymphoma: a 10-year follow-up analysis of the JCOG0203 trial. Lancet Haematol. 2018 Nov;5(11):e520-e531. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(18)30155-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30389034 PubMed]
 <!-- # '''Abstract:''' Ian Flinn et al. An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study. 2012 ASH Annual Meeting abstract 902. [https://ash.confex.com/ash/2012/webprogram/Paper51442.html link to abstract] -->
-# '''SWOG S0016:''' Press OW, Unger JM, Rimsza LM, Friedberg JW, LeBlanc M, Czuczman MS, Kaminski M, Braziel RM, Spier C, Gopal AK, Maloney DG, Cheson BD, Dakhil SR, Miller TP, Fisher RI. Phase III randomized intergroup trial of CHOP plus rituximab compared with CHOP chemotherapy plus 131Iodine-tositumomab for previously untreated follicular non-Hodgkin lymphoma: SWOG S0016. J Clin Oncol. 2013 Jan 20;31(3):314-20. Epub 2012 Dec 10. [http://jco.ascopubs.org/content/31/3/314.full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732010/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23233710 PubMed]
+#'''SWOG S0016:''' Press OW, Unger JM, Rimsza LM, Friedberg JW, LeBlanc M, Czuczman MS, Kaminski M, Braziel RM, Spier C, Gopal AK, Maloney DG, Cheson BD, Dakhil SR, Miller TP, Fisher RI. Phase III randomized intergroup trial of CHOP plus rituximab compared with CHOP chemotherapy plus 131Iodine-tositumomab for previously untreated follicular non-Hodgkin lymphoma: SWOG S0016. J Clin Oncol. 2013 Jan 20;31(3):314-20. Epub 2012 Dec 10. [http://jco.ascopubs.org/content/31/3/314.full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732010/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23233710 PubMed]
-## '''Update:''' Shadman M, Li H, Rimsza L, Leonard JP, Kaminski MS, Braziel RM, Spier CM, Gopal AK, Maloney DG, Cheson BD, Dakhil S, LeBlanc M, Smith SM, Fisher RI, Friedberg JW, Press OW. Continued excellent outcomes in previously untreated patients with follicular lymphoma after treatment with CHOP plus rituximab or CHOP plus (131)I-tositumomab: long-term follow-up of phase III randomized study SWOG-S0016. J Clin Oncol. 2018 Mar 1;36(7):697-703. Epub 2018 Jan 22. [https://ascopubs.org/doi/full/10.1200/JCO.2017.74.5083 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29356608 PubMed]
+##'''Update:''' Shadman M, Li H, Rimsza L, Leonard JP, Kaminski MS, Braziel RM, Spier CM, Gopal AK, Maloney DG, Cheson BD, Dakhil S, LeBlanc M, Smith SM, Fisher RI, Friedberg JW, Press OW. Continued excellent outcomes in previously untreated patients with follicular lymphoma after treatment with CHOP plus rituximab or CHOP plus (131)I-tositumomab: long-term follow-up of phase III randomized study SWOG-S0016. J Clin Oncol. 2018 Mar 1;36(7):697-703. Epub 2018 Jan 22. [https://ascopubs.org/doi/full/10.1200/JCO.2017.74.5083 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29356608 PubMed]
 <!-- # '''Abstract:''' Mathias J. Rummel, Norbert Niederle, Georg Maschmeyer, Andre G. Banat, Ulrich von Gruenhagen, Christoph Losem, Dorothea Kofahl-Krause, Gerhard Heil, Manfred Welslau, Christina Balser, Ulrich Kaiser, Eckhart Weidmann, Heinz A. Duerk, Harald Ballo, Martina Stauch, Juergen Barth, Axel Hinke, Wolfram Brugger, Study Group Indolent Lymphomas (StiL). Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent and mantle cell lymphomas (MCL): Updated results from the StiL NHL1 study. 2012 ASCO Annual Meeting abstract 3. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview==abst_detail_view&confID==114&abstractID==95807 link to abstract] [http://www.ascopost.com/issues/july-1-2012/german-study-finds-bendamustine-improves-progression-free-survival-in-patients-with-non-hodgkin-lymphoma.aspx ASCO Post article] [http://www.asco.org/ASCOv2/MultiMedia/Virtual%20Meeting?&vmview==vm_session_presentations_view&confID==114&sessionID==4807 ASCO plenary session video] -->
-# '''StiL NHL1:''' Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Dürk H, Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W; Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013 Apr 6;381(9873):1203-10. Epub 2013 Feb 20. Erratum in: Lancet. 2013 Apr 6;381(9873):1184. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2961763-2/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23433739 PubMed]
+#'''StiL NHL1:''' Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Dürk H, Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W; Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013 Apr 6;381(9873):1203-10. Epub 2013 Feb 20. Erratum in: Lancet. 2013 Apr 6;381(9873):1184. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2961763-2/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23433739 PubMed]
-## '''Update: Abstract:''' Mathias J. Rummel, MD, Georg Maschmeyer, MD, Arnold Ganser, Andrea Heider, PhD, Ulrich von Grünhagen, MD, PhD5, Christoph Losem, Gerhard Heil, MD, Manfred Welslau, Christina Balser, MD, Ulrich Kaiser, MD, Eckhart Weidmann, Heinz Dürk, MD, Hans Peter Böck, Martina Beate Stauch, MD, Jürgen Barth, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Axel Hinke, PhD and Wolfram Brugger, MD. Bendamustine Plus Rituximab (B-R) Versus CHOP Plus Rituximab (CHOP-R) As First-Line Treatment in Patients with Indolent and Mantle Cell Lymphomas (MCL) – 7 Year Updated Results from the StiL NHL1 Study. Blood 2014 124:4407. [http://www.bloodjournal.org/content/124/21/4407 link to abstract]
+##'''Update: Abstract:''' Mathias J. Rummel, MD, Georg Maschmeyer, MD, Arnold Ganser, Andrea Heider, PhD, Ulrich von Grünhagen, MD, PhD5, Christoph Losem, Gerhard Heil, MD, Manfred Welslau, Christina Balser, MD, Ulrich Kaiser, MD, Eckhart Weidmann, Heinz Dürk, MD, Hans Peter Böck, Martina Beate Stauch, MD, Jürgen Barth, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Axel Hinke, PhD and Wolfram Brugger, MD. Bendamustine Plus Rituximab (B-R) Versus CHOP Plus Rituximab (CHOP-R) As First-Line Treatment in Patients with Indolent and Mantle Cell Lymphomas (MCL) – 7 Year Updated Results from the StiL NHL1 Study. Blood 2014 124:4407. [http://www.bloodjournal.org/content/124/21/4407 link to abstract]
-## '''Update: Abstract:''' Mathias J. Rummel, Georg Maschmeyer, Arnold Ganser, Andrea Heider, Ulrich von Gruenhagen, Christoph Losem, Gerhard Heil, Manfred Welslau, Christina Balser, Ulrich Kaiser, Eckhart Weidmann, Heinz Albert Dürk, Harald Ballo, Martina Stauch, Wolfgang Blau, Alexander Burchardt, Juergen Barth, Frank Kauff, and Wolfram Brugger. Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent lymphomas: Nine-year updated results from the StiL NHL1 study. Journal of Clinical Oncology 2017 35:15_suppl, 7501-7501 [https://ascopubs.org/doi/full/10.1200/JCO.2017.35.15_suppl.7501 link to abstract]
+##'''Update: Abstract:''' Mathias J. Rummel, Georg Maschmeyer, Arnold Ganser, Andrea Heider, Ulrich von Gruenhagen, Christoph Losem, Gerhard Heil, Manfred Welslau, Christina Balser, Ulrich Kaiser, Eckhart Weidmann, Heinz Albert Dürk, Harald Ballo, Martina Stauch, Wolfgang Blau, Alexander Burchardt, Juergen Barth, Frank Kauff, and Wolfram Brugger. Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent lymphomas: Nine-year updated results from the StiL NHL1 study. Journal of Clinical Oncology 2017 35:15_suppl, 7501-7501 [https://ascopubs.org/doi/full/10.1200/JCO.2017.35.15_suppl.7501 link to abstract]
-# '''FOLL05:''' Federico M, Luminari S, Dondi A, Tucci A, Vitolo U, Rigacci L, Di Raimondo F, Carella AM, Pulsoni A, Merli F, Arcaini L, Angrilli F, Stelitano C, Gaidano G, Dell'olio M, Marcheselli L, Franco V, Galimberti S, Sacchi S, Brugiatelli M. R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage follicular lymphoma: results of the FOLL05 trial conducted by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Apr 20;31(12):1506-13. Epub 2013 Mar 25. Erratum in: J Clin Oncol. 2014 Apr 1;32(10):1095. Dosage error in article text. [http://jco.ascopubs.org/content/31/12/1506.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23530110 PubMed]
+#'''FOLL05:''' Federico M, Luminari S, Dondi A, Tucci A, Vitolo U, Rigacci L, Di Raimondo F, Carella AM, Pulsoni A, Merli F, Arcaini L, Angrilli F, Stelitano C, Gaidano G, Dell'olio M, Marcheselli L, Franco V, Galimberti S, Sacchi S, Brugiatelli M. R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage follicular lymphoma: results of the FOLL05 trial conducted by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Apr 20;31(12):1506-13. Epub 2013 Mar 25. Erratum in: J Clin Oncol. 2014 Apr 1;32(10):1095. Dosage error in article text. [http://jco.ascopubs.org/content/31/12/1506.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23530110 PubMed]
 <!-- ## '''Update: Abstract:''' Stefano Luminari, Alessandra Dondi, Luigi Marcheselli, Giuseppe Rossi, Carola Boccomini, Annalisa Chiarenza, Luigi Rigacci, Francesco Merli, Giovanni Bertoldero, Alessandro Levis, Andres J. Ferreri, Daniele Vallisa, Maria Christina Cox, Monica Balzarotti, Massimiliano Salati, Massimo Federico. Updated results of the FOLL05 phase III trial from the Fondazione Italiana Linfomi comparing R-CVP, R-CHOP, and R-FM in patients with advanced follicular lymphoma. J Clin Oncol 32:5s, 2014 (suppl; abstr 8530) [http://meetinglibrary.asco.org/content/131262-144 link to abstract] -->
-## '''Update:''' Luminari S, Ferrari A, Manni M, Dondi A, Chiarenza A, Merli F, Rusconi C, Tarantino V, Tucci A, Vitolo U, Kovalchuk S, Angelucci E, Pulsoni A, Arcaini L, Angrilli F, Gaidano G, Stelitano C, Bertoldero G, Cascavilla N, Salvi F, Ferreri AJM, Vallisa D, Marcheselli L, Federico M. Long-term results of the FOLL05 trial comparing R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage symptomatic follicular lymphoma. J Clin Oncol. 2018 Mar 1;36(7):689-696. Epub 2017 Nov 2. [https://ascopubs.org/doi/full/10.1200/JCO.2017.74.1652 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29095677 PubMed]
+##'''Update:''' Luminari S, Ferrari A, Manni M, Dondi A, Chiarenza A, Merli F, Rusconi C, Tarantino V, Tucci A, Vitolo U, Kovalchuk S, Angelucci E, Pulsoni A, Arcaini L, Angrilli F, Gaidano G, Stelitano C, Bertoldero G, Cascavilla N, Salvi F, Ferreri AJM, Vallisa D, Marcheselli L, Federico M. Long-term results of the FOLL05 trial comparing R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage symptomatic follicular lymphoma. J Clin Oncol. 2018 Mar 1;36(7):689-696. Epub 2017 Nov 2. [https://ascopubs.org/doi/full/10.1200/JCO.2017.74.1652 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29095677 PubMed]
-# '''Abstract:''' Armando Lopez-Guillermo, MD, PhD, Miguel A. Canales, MD, PhD, Ivan Dlouhy, Javier Briones, MD, Dolores Caballero, MD, PhD, Juan Manuel Sancho Sr., MD, Santiago Mercadal Vilchez, MD, Jose María Moraleda, MD, María José Terol, MD, PhD, Antonio Salar, MD, Luis Palomera, MD, Santiago Gardella, MD, Isidro Jarque, MD, Secundino Ferrer, Joan Bargay, MD, Andres Lopez, Carlos Panizo, Anna Muntanola, MD, Carlos Montalban, Eulogio Conde, MD, PhD, Miguel Hernandez, MD, Alfons Soler, Julian Marin, MD, Jose García Marco, Guillermo Deben and José Francisco Tomas, MD, PhD. A Randomized Phase II Study Comparing Consolidation With a Single Dose Of 90y Ibritumomab Tiuxetan (Zevalin®) (Z) Vs. Maintenance With Rituximab (R) For Two Years In Patients With Newly Diagnosed Follicular Lymphoma (FL) Responding To R-CHOP. Preliminary Results At 36 Months From Randomization. Blood 2013 122:369. [http://www.bloodjournal.org/content/122/21/369 link to abstract]
+#'''Abstract:''' Armando Lopez-Guillermo, MD, PhD, Miguel A. Canales, MD, PhD, Ivan Dlouhy, Javier Briones, MD, Dolores Caballero, MD, PhD, Juan Manuel Sancho Sr., MD, Santiago Mercadal Vilchez, MD, Jose María Moraleda, MD, María José Terol, MD, PhD, Antonio Salar, MD, Luis Palomera, MD, Santiago Gardella, MD, Isidro Jarque, MD, Secundino Ferrer, Joan Bargay, MD, Andres Lopez, Carlos Panizo, Anna Muntanola, MD, Carlos Montalban, Eulogio Conde, MD, PhD, Miguel Hernandez, MD, Alfons Soler, Julian Marin, MD, Jose García Marco, Guillermo Deben and José Francisco Tomas, MD, PhD. A Randomized Phase II Study Comparing Consolidation With a Single Dose Of 90y Ibritumomab Tiuxetan (Zevalin®) (Z) Vs. Maintenance With Rituximab (R) For Two Years In Patients With Newly Diagnosed Follicular Lymphoma (FL) Responding To R-CHOP. Preliminary Results At 36 Months From Randomization. Blood 2013 122:369. [http://www.bloodjournal.org/content/122/21/369 link to abstract]
-# '''BRIGHT:''' Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. [http://bloodjournal.org/content/123/19/2944.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24591201 PubMed]
+#'''BRIGHT:''' Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. [http://bloodjournal.org/content/123/19/2944.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24591201 PubMed]
 <!-- ## '''Update: Abstract:''' Ian Flinn, Richard van der Jagt, Julie E. Chang, Peter Wood, Tim E. Hawkins, David MacDonald, Judith Trotman, David Simpson, Kathryn S. Kolibaba, Samar Issa, Doreen M. Hallman, Ling Chen, and John M. Burke. First-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP: Results of the BRIGHT 5-year follow-up study. Journal of Clinical Oncology 2017 35:15_suppl, 7500-7500 [https://ascopubs.org/doi/full/10.1200/JCO.2017.35.15_suppl.7500 link to abstract] -->
-## '''Update:''' Flinn IW, van der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, Simpson D, Kolibaba K, Issa S, Chang J, Trotman J, Hallman D, Chen L, Burke JM. First-line treatment of patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma with bendamustine plus rituximab versus R-CHOP or R-CVP: results of the BRIGHT 5-year follow-up study. J Clin Oncol. 2019 Apr 20;37(12):984-991. Epub 2019 Feb 27. [https://ascopubs.org/doi/full/10.1200/JCO.18.00605 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494265/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30811293 PubMed]
+##'''Update:''' Flinn IW, van der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, Simpson D, Kolibaba K, Issa S, Chang J, Trotman J, Hallman D, Chen L, Burke JM. First-line treatment of patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma with bendamustine plus rituximab versus R-CHOP or R-CVP: results of the BRIGHT 5-year follow-up study. J Clin Oncol. 2019 Apr 20;37(12):984-991. Epub 2019 Feb 27. [https://ascopubs.org/doi/full/10.1200/JCO.18.00605 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494265/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30811293 PubMed]
-# '''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://www.nejm.org/doi/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains verified protocol in appendix''' [https://www.ncbi.nlm.nih.gov/pubmed/28976863 PubMed]
+#'''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://www.nejm.org/doi/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains verified protocol in appendix''' [https://www.ncbi.nlm.nih.gov/pubmed/28976863 PubMed]
-## '''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8960 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29856692 PubMed]
+##'''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8960 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29856692 PubMed]
-# '''RELEVANCE:''' Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. [https://www.nejm.org/doi/full/10.1056/NEJMoa1805104 link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/30184451 PubMed]
+#'''RELEVANCE:''' Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. [https://www.nejm.org/doi/full/10.1056/NEJMoa1805104 link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/30184451 PubMed]
 ==R-CHVP+I {{#subobject:1b5df7|Regimen=1}}==
@@ Line 828: / Line 892: @@
 ===Regimen {{#subobject:1593ec|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.bloodjournal.org/content/112/13/4824.full Salles et al. 2008 (FL2000)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |CHVP+I
-|style="background-color:#1a9850"|Superior EFS
+| style="background-color:#1a9850" |Superior EFS
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows:
 **Cycles 3 & 4: 375 mg/m<sup>2</sup> IV once per day on days 1 and 8
 **Cycles 5 & 6: 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
@@ Line 850: / Line 915: @@
 '''28-day cycle for 6 cycles'''
 ====Subsequent treatment====
 *[[#Interferon_alfa-2a_monotherapy|Interferon alfa-2a maintenance]]
 ===References===
-# '''FL2000:''' Salles G, Mounier N, de Guibert S, Morschhauser F, Doyen C, Rossi JF, Haioun C, Brice P, Mahé B, Bouabdallah R, Audhuy B, Ferme C, Dartigeas C, Feugier P, Sebban C, Xerri L, Foussard C. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood. 2008 Dec 15;112(13):4824-31. Epub 2008 Sep 17. [http://www.bloodjournal.org/content/112/13/4824.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18799723 PubMed]
-## '''Update:''' Bachy E, Houot R, Morschhauser F, Sonet A, Brice P, Belhadj K, Cartron G, Audhuy B, Fermé C, Feugier P, Sebban C, Delwail V, Maisonneuve H, Le Gouill S, Lefort S, Brousse N, Foussard C, Salles G; Groupe d'Etude des Lymphomes de l'Adulte (GELA). Long-term follow up of the FL2000 study comparing CHVP-interferon to CHVP-interferon plus rituximab in follicular lymphoma. Haematologica. 2013 Jul;98(7):1107-14. Epub 2013 May 3. [http://www.haematologica.org/content/98/7/1107.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696615/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23645690 PubMed]
+#'''FL2000:''' Salles G, Mounier N, de Guibert S, Morschhauser F, Doyen C, Rossi JF, Haioun C, Brice P, Mahé B, Bouabdallah R, Audhuy B, Ferme C, Dartigeas C, Feugier P, Sebban C, Xerri L, Foussard C. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood. 2008 Dec 15;112(13):4824-31. Epub 2008 Sep 17. [http://www.bloodjournal.org/content/112/13/4824.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18799723 PubMed]
+##'''Update:''' Bachy E, Houot R, Morschhauser F, Sonet A, Brice P, Belhadj K, Cartron G, Audhuy B, Fermé C, Feugier P, Sebban C, Delwail V, Maisonneuve H, Le Gouill S, Lefort S, Brousse N, Foussard C, Salles G; Groupe d'Etude des Lymphomes de l'Adulte (GELA). Long-term follow up of the FL2000 study comparing CHVP-interferon to CHVP-interferon plus rituximab in follicular lymphoma. Haematologica. 2013 Jul;98(7):1107-14. Epub 2013 May 3. [http://www.haematologica.org/content/98/7/1107.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696615/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23645690 PubMed]
 ==R-CVP {{#subobject:dff264|Regimen=1}}==
@@ Line 864: / Line 931: @@
 ===Variant #1, prednisone 40 mg/m<sup>2</sup> {{#subobject:432427|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[http://www.bloodjournal.org/content/105/4/1417.full Marcus et al. 2005]
-|style="background-color:#1a9851"|Phase III (E-RT-esc)
+| style="background-color:#1a9851" |Phase III (E-RT-esc)
 |[[Follicular_lymphoma_-_historical#CVP|CVP]]
-|style="background-color:#1a9850"|Superior TTP
+| style="background-color:#1a9850" |Superior TTP
-|style="background-color:#91cf61"|Similar toxicity
+| style="background-color:#91cf61" |Similar toxicity
 |-
 |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2962175-7/fulltext Salles et al. 2010 (PRIMA)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
-|rowspan=2|[http://jco.ascopubs.org/content/31/12/1506.long Federico et al. 2013 (FOLL05)]
+| rowspan="2" |[http://jco.ascopubs.org/content/31/12/1506.long Federico et al. 2013 (FOLL05)]
-|rowspan=2 style="background-color:#1a9851"|Phase III (E-de-esc)
+| rowspan="2" style="background-color:#1a9851" |Phase III (E-de-esc)
 |1. [[#R-CHOP|R-CHOP]]
-|style="background-color:#fc8d59"|Seems to have inferior PFS
+| style="background-color:#fc8d59" |Seems to have inferior PFS
-|style="background-color:#91cf61"|See paper
+| style="background-color:#91cf61" |See paper
 |-
 |2. [[#R-FM|R-FM]]
 | style="background-color:#d73027" |Inferior PFS (*)
-|style="background-color:#91cf61"|See paper
+| style="background-color:#91cf61" |See paper
 |-
 |[https://www.nejm.org/doi/full/10.1056/NEJMoa1805104 Morschhauser et al. 2018 (RELEVANCE)]
@@ Line 901: / Line 968: @@
 ''Note: reported efficacy for FOLL05 for comparison marked with (*) is based on the 2017 update.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 908: / Line 976: @@
 '''21-day cycle for up to 8 cycles'''
 ====Subsequent treatment====
 *PRIMA, responders (PR or CR): [[#Rituximab_monotherapy.2C_extended_course|Rituximab maintenance]] versus [[#Observation_3|no further treatment]]
 *RELEVANCE, responders: [[#Rituximab_monotherapy.2C_extended_course|Rituximab maintenance]]
@@ Line 913: / Line 982: @@
 ===Variant #2, prednisone 100 mg/day {{#subobject:dad22|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ Flinn et al. 2014 (BRIGHT)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#BR|BR]]
-|style="background-color:#eeee01"|Seems to have non-inferior CR rate
+| style="background-color:#eeee01" |Seems to have non-inferior CR rate
 |
 |-
@@ Line 934: / Line 1,003: @@
 ''Patients in BRIGHT were required to be treatment-naive with a need for treatment per any of the following: B symptoms, large tumor mass (lymphomas with a diameter greater than 3 cm in 3 or more regions or diameter greater than 7 cm in 1 region), presence of lymphoma-related complications, or hyperviscosity syndrome attributed to monoclonal gammopathy. Patients in GALLIUM received rituximab only in cycles 7 & 8.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 941: / Line 1,011: @@
 ====Supportive medications====
 *Antiemetics, antipyretics, and antibiotics per local standard of care
 *[[:Category:Granulocyte colony-stimulating factors|G-CSF]] "according to the [http://jco.ascopubs.org/content/18/20/3558.full American Society of Clinical Oncology guidelines]"
@@ Line 946: / Line 1,017: @@
 '''21-day cycle for up to 8 cycles'''
 ====Subsequent treatment====
 *GALLIUM: [[#Rituximab_monotherapy.2C_extended_course|Rituximab maintenance]]
 ===Variant #3, 3 cycles {{#subobject:b7ff27|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://jco.ascopubs.org/content/23/7/1500.long Hainsworth et al. 2005a]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Preceding treatment====
 *[[#Rituximab_monotherapy|Rituximab pre-phase]] x 4
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
@@ Line 968: / Line 1,043: @@
 ====Subsequent treatment====
 *[[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab consolidation]]
 ===References===
-# Hainsworth JD, Litchy S, Morrissey LH, Andrews MB, Grimaldi M, McCarty M, Greco FA. Rituximab plus short-duration chemotherapy as first-line treatment for follicular non-Hodgkin's lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Mar 1;23(7):1500-6. Epub 2005 Jan 4. [http://jco.ascopubs.org/content/23/7/1500.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15632411 PubMed]
-# Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J, Solal-Celigny P, Offner F, Walewski J, Raposo J, Jack A, Smith P. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005 Feb 15;105(4):1417-23. [http://www.bloodjournal.org/content/105/4/1417.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15494430 PubMed]
+#Hainsworth JD, Litchy S, Morrissey LH, Andrews MB, Grimaldi M, McCarty M, Greco FA. Rituximab plus short-duration chemotherapy as first-line treatment for follicular non-Hodgkin's lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Mar 1;23(7):1500-6. Epub 2005 Jan 4. [http://jco.ascopubs.org/content/23/7/1500.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15632411 PubMed]
-## '''Update:''' Marcus R, Imrie K, Solal-Celigny P, Catalano JV, Dmoszynska A, Raposo JC, Offner FC, Gomez-Codina J, Belch A, Cunningham D, Wassner-Fritsch E, Stein G. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol. 2008 Oct 1;26(28):4579-86. Epub 2008 Jul 28. [http://jco.ascopubs.org/content/26/28/4579.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18662969 PubMed]
+#Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J, Solal-Celigny P, Offner F, Walewski J, Raposo J, Jack A, Smith P. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005 Feb 15;105(4):1417-23. [http://www.bloodjournal.org/content/105/4/1417.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15494430 PubMed]
-# '''PRIMA:''' Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2962175-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21176949 PubMed]
+##'''Update:''' Marcus R, Imrie K, Solal-Celigny P, Catalano JV, Dmoszynska A, Raposo JC, Offner FC, Gomez-Codina J, Belch A, Cunningham D, Wassner-Fritsch E, Stein G. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol. 2008 Oct 1;26(28):4579-86. Epub 2008 Jul 28. [http://jco.ascopubs.org/content/26/28/4579.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18662969 PubMed]
-## '''QoL Analysis:''' Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. [http://www.maneyonline.com/doi/full/10.1179/1607845414Y.0000000179 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25029908 PubMed]
+#'''PRIMA:''' Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2962175-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21176949 PubMed]
-## '''Update:''' Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. [https://ascopubs.org/doi/full/10.1200/JCO.19.01073 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823890/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/31339826 PubMed]
+##'''QoL Analysis:''' Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. [http://www.maneyonline.com/doi/full/10.1179/1607845414Y.0000000179 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25029908 PubMed]
-# '''FOLL05:''' Federico M, Luminari S, Dondi A, Tucci A, Vitolo U, Rigacci L, Di Raimondo F, Carella AM, Pulsoni A, Merli F, Arcaini L, Angrilli F, Stelitano C, Gaidano G, Dell'olio M, Marcheselli L, Franco V, Galimberti S, Sacchi S, Brugiatelli M. R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage follicular lymphoma: results of the FOLL05 trial conducted by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Apr 20;31(12):1506-13. Epub 2013 Mar 25. Erratum in: J Clin Oncol. 2014 Apr 1;32(10):1095. Dosage error in article text. [http://jco.ascopubs.org/content/31/12/1506.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23530110 PubMed]
+##'''Update:''' Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. [https://ascopubs.org/doi/full/10.1200/JCO.19.01073 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823890/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/31339826 PubMed]
+#'''FOLL05:''' Federico M, Luminari S, Dondi A, Tucci A, Vitolo U, Rigacci L, Di Raimondo F, Carella AM, Pulsoni A, Merli F, Arcaini L, Angrilli F, Stelitano C, Gaidano G, Dell'olio M, Marcheselli L, Franco V, Galimberti S, Sacchi S, Brugiatelli M. R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage follicular lymphoma: results of the FOLL05 trial conducted by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Apr 20;31(12):1506-13. Epub 2013 Mar 25. Erratum in: J Clin Oncol. 2014 Apr 1;32(10):1095. Dosage error in article text. [http://jco.ascopubs.org/content/31/12/1506.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23530110 PubMed]
 <!-- ## '''Update: Abstract:''' Stefano Luminari, Alessandra Dondi, Luigi Marcheselli, Giuseppe Rossi, Carola Boccomini, Annalisa Chiarenza, Luigi Rigacci, Francesco Merli, Giovanni Bertoldero, Alessandro Levis, Andres J. Ferreri, Daniele Vallisa, Maria Christina Cox, Monica Balzarotti, Massimiliano Salati, Massimo Federico. Updated results of the FOLL05 phase III trial from the Fondazione Italiana Linfomi comparing R-CVP, R-CHOP, and R-FM in patients with advanced follicular lymphoma. J Clin Oncol 32:5s, 2014 (suppl; abstr 8530) [http://meetinglibrary.asco.org/content/131262-144 link to abstract] -->
-## '''Update:''' Luminari S, Ferrari A, Manni M, Dondi A, Chiarenza A, Merli F, Rusconi C, Tarantino V, Tucci A, Vitolo U, Kovalchuk S, Angelucci E, Pulsoni A, Arcaini L, Angrilli F, Gaidano G, Stelitano C, Bertoldero G, Cascavilla N, Salvi F, Ferreri AJM, Vallisa D, Marcheselli L, Federico M. Long-term results of the FOLL05 trial comparing R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage symptomatic follicular lymphoma. J Clin Oncol. 2018 Mar 1;36(7):689-696. Epub 2017 Nov 2. [https://ascopubs.org/doi/full/10.1200/JCO.2017.74.1652 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29095677 PubMed]
+##'''Update:''' Luminari S, Ferrari A, Manni M, Dondi A, Chiarenza A, Merli F, Rusconi C, Tarantino V, Tucci A, Vitolo U, Kovalchuk S, Angelucci E, Pulsoni A, Arcaini L, Angrilli F, Gaidano G, Stelitano C, Bertoldero G, Cascavilla N, Salvi F, Ferreri AJM, Vallisa D, Marcheselli L, Federico M. Long-term results of the FOLL05 trial comparing R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage symptomatic follicular lymphoma. J Clin Oncol. 2018 Mar 1;36(7):689-696. Epub 2017 Nov 2. [https://ascopubs.org/doi/full/10.1200/JCO.2017.74.1652 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29095677 PubMed]
 <!-- # '''Abstract:''' Ian Flinn et al. An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study. 2012 ASH Annual Meeting abstract 902. [https://ash.confex.com/ash/2012/webprogram/Paper51442.html link to abstract] -->
-# '''BRIGHT:''' Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. [http://bloodjournal.org/content/123/19/2944.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24591201 PubMed]
+#'''BRIGHT:''' Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. [http://bloodjournal.org/content/123/19/2944.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24591201 PubMed]
 <!-- ## '''Update: Abstract:''' Ian Flinn, Richard van der Jagt, Julie E. Chang, Peter Wood, Tim E. Hawkins, David MacDonald, Judith Trotman, David Simpson, Kathryn S. Kolibaba, Samar Issa, Doreen M. Hallman, Ling Chen, and John M. Burke. First-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP: Results of the BRIGHT 5-year follow-up study. Journal of Clinical Oncology 2017 35:15_suppl, 7500-7500 [https://ascopubs.org/doi/full/10.1200/JCO.2017.35.15_suppl.7500 link to abstract] -->
-## '''Update:''' Flinn IW, van der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, Simpson D, Kolibaba K, Issa S, Chang J, Trotman J, Hallman D, Chen L, Burke JM. First-line treatment of patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma with bendamustine plus rituximab versus R-CHOP or R-CVP: results of the BRIGHT 5-year follow-up study. J Clin Oncol. 2019 Apr 20;37(12):984-991. Epub 2019 Feb 27. [https://ascopubs.org/doi/full/10.1200/JCO.18.00605 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494265/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30811293 PubMed]
+##'''Update:''' Flinn IW, van der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, Simpson D, Kolibaba K, Issa S, Chang J, Trotman J, Hallman D, Chen L, Burke JM. First-line treatment of patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma with bendamustine plus rituximab versus R-CHOP or R-CVP: results of the BRIGHT 5-year follow-up study. J Clin Oncol. 2019 Apr 20;37(12):984-991. Epub 2019 Feb 27. [https://ascopubs.org/doi/full/10.1200/JCO.18.00605 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494265/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30811293 PubMed]
-# '''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://www.nejm.org/doi/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains verified protocol in appendix''' [https://www.ncbi.nlm.nih.gov/pubmed/28976863 PubMed]
+#'''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://www.nejm.org/doi/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains verified protocol in appendix''' [https://www.ncbi.nlm.nih.gov/pubmed/28976863 PubMed]
-## '''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8960 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29856692 PubMed]
+##'''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8960 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29856692 PubMed]
-# '''RELEVANCE:''' Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. [https://www.nejm.org/doi/full/10.1056/NEJMoa1805104 link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/30184451 PubMed]
+#'''RELEVANCE:''' Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. [https://www.nejm.org/doi/full/10.1056/NEJMoa1805104 link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/30184451 PubMed]
 ==R-FM {{#subobject:cd6200|Regimen=1}}==
@@ Line 996: / Line 1,074: @@
 ===Variant #1, 4 cycles {{#subobject:5285e6|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://annonc.oxfordjournals.org/content/23/2/415.long Zinzani et al. 2011]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days 2 to 4
 *[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once on day 2
@@ Line 1,009: / Line 1,088: @@
 ====Supportive medications====
 *No prophylactic use of [[:Category:Granulocyte colony-stimulating factors|G-CSF]], but patients with grade 3 or 4 neutropenia or delayed neutropenic fever could be given growth factors for later cycles at physician discretion
 '''28-day cycle for 4 cycles'''
 ====Subsequent treatment====
 *Patients were restaged 2 to 3 weeks after finishing cycle 4. People with at least a partial response (PR), ANC greater than 1500/uL, platelet count greater than 100 x 10<sup>9</sup>/L, and less than 25% bone marrow involvement were eligible for [[#Ibritumomab_tiuxetan_monotherapy_3|consolidation therapy with ibritumomab tiuxetan]], given within 12 weeks (paper does not specify "within 12 weeks" of what)
 ===Variant #2, 8 cycles {{#subobject:41cd4b|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|rowspan=2|[http://jco.ascopubs.org/content/31/12/1506.long Federico et al. 2013 (FOLL05)]
+| rowspan="2" |[http://jco.ascopubs.org/content/31/12/1506.long Federico et al. 2013 (FOLL05)]
-|rowspan=2 style="background-color:#1a9851"|Phase III (E-switch-ic)
+| rowspan="2" style="background-color:#1a9851" |Phase III (E-switch-ic)
 |1. [[#R-CHOP|R-CHOP]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of TTF
+| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
 |-
 |2. [[#R-CVP|R-CVP]]
@@ Line 1,033: / Line 1,114: @@
 ''Note: risk/benefit ratio was worse than R-CHOP. Reported efficacy for comparison marked with (*) is based on the 2017 update.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Fludarabine (Fludara)]] as follows:
@@ Line 1,042: / Line 1,124: @@
 ===References===
-# Zinzani PL, Tani M, Pulsoni A, De Renzo A, Stefoni V, Broccoli A, Montini GC, Fina M, Pellegrini C, Gandolfi L, Cavalieri E, Torelli F, Scopinaro F, Argnani L, Quirini F, Derenzini E, Rossi M, Pileri S, Fanti S, Baccarani M. A phase II trial of short course fludarabine, mitoxantrone, rituximab followed by <sup>90</sup>Y-ibritumomab tiuxetan in untreated intermediate/high-risk follicular lymphoma. Ann Oncol. 2012 Feb;23(2):415-20. Epub 2011 May 2. [http://annonc.oxfordjournals.org/content/23/2/415.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21536660 PubMed]
-# '''FOLL05:''' Federico M, Luminari S, Dondi A, Tucci A, Vitolo U, Rigacci L, Di Raimondo F, Carella AM, Pulsoni A, Merli F, Arcaini L, Angrilli F, Stelitano C, Gaidano G, Dell'olio M, Marcheselli L, Franco V, Galimberti S, Sacchi S, Brugiatelli M. R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage follicular lymphoma: results of the FOLL05 trial conducted by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Apr 20;31(12):1506-13. Epub 2013 Mar 25. Erratum in: J Clin Oncol. 2014 Apr 1;32(10):1095. Dosage error in article text. [http://jco.ascopubs.org/content/31/12/1506.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23530110 PubMed]
+#Zinzani PL, Tani M, Pulsoni A, De Renzo A, Stefoni V, Broccoli A, Montini GC, Fina M, Pellegrini C, Gandolfi L, Cavalieri E, Torelli F, Scopinaro F, Argnani L, Quirini F, Derenzini E, Rossi M, Pileri S, Fanti S, Baccarani M. A phase II trial of short course fludarabine, mitoxantrone, rituximab followed by <sup>90</sup>Y-ibritumomab tiuxetan in untreated intermediate/high-risk follicular lymphoma. Ann Oncol. 2012 Feb;23(2):415-20. Epub 2011 May 2. [http://annonc.oxfordjournals.org/content/23/2/415.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21536660 PubMed]
+#'''FOLL05:''' Federico M, Luminari S, Dondi A, Tucci A, Vitolo U, Rigacci L, Di Raimondo F, Carella AM, Pulsoni A, Merli F, Arcaini L, Angrilli F, Stelitano C, Gaidano G, Dell'olio M, Marcheselli L, Franco V, Galimberti S, Sacchi S, Brugiatelli M. R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage follicular lymphoma: results of the FOLL05 trial conducted by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Apr 20;31(12):1506-13. Epub 2013 Mar 25. Erratum in: J Clin Oncol. 2014 Apr 1;32(10):1095. Dosage error in article text. [http://jco.ascopubs.org/content/31/12/1506.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23530110 PubMed]
 <!-- ## '''Update: Abstract:''' Stefano Luminari, Alessandra Dondi, Luigi Marcheselli, Giuseppe Rossi, Carola Boccomini, Annalisa Chiarenza, Luigi Rigacci, Francesco Merli, Giovanni Bertoldero, Alessandro Levis, Andres J. Ferreri, Daniele Vallisa, Maria Christina Cox, Monica Balzarotti, Massimiliano Salati, Massimo Federico. Updated results of the FOLL05 phase III trial from the Fondazione Italiana Linfomi comparing R-CVP, R-CHOP, and R-FM in patients with advanced follicular lymphoma. J Clin Oncol 32:5s, 2014 (suppl; abstr 8530) [http://meetinglibrary.asco.org/content/131262-144 link to abstract] -->
-## '''Update:''' Luminari S, Ferrari A, Manni M, Dondi A, Chiarenza A, Merli F, Rusconi C, Tarantino V, Tucci A, Vitolo U, Kovalchuk S, Angelucci E, Pulsoni A, Arcaini L, Angrilli F, Gaidano G, Stelitano C, Bertoldero G, Cascavilla N, Salvi F, Ferreri AJM, Vallisa D, Marcheselli L, Federico M. Long-term results of the FOLL05 trial comparing R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage symptomatic follicular lymphoma. J Clin Oncol. 2018 Mar 1;36(7):689-696. Epub 2017 Nov 2. [https://ascopubs.org/doi/full/10.1200/JCO.2017.74.1652 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29095677 PubMed]
+##'''Update:''' Luminari S, Ferrari A, Manni M, Dondi A, Chiarenza A, Merli F, Rusconi C, Tarantino V, Tucci A, Vitolo U, Kovalchuk S, Angelucci E, Pulsoni A, Arcaini L, Angrilli F, Gaidano G, Stelitano C, Bertoldero G, Cascavilla N, Salvi F, Ferreri AJM, Vallisa D, Marcheselli L, Federico M. Long-term results of the FOLL05 trial comparing R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage symptomatic follicular lymphoma. J Clin Oncol. 2018 Mar 1;36(7):689-696. Epub 2017 Nov 2. [https://ascopubs.org/doi/full/10.1200/JCO.2017.74.1652 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29095677 PubMed]
 ==R-FND {{#subobject:17bb83|Regimen=1}}==
@@ Line 1,056: / Line 1,139: @@
 ===Regimen {{#subobject:9fd3ee|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://jco.ascopubs.org/content/31/27/3351.full Vitolo et al. 2013 (ML17638)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days 2 to 4
@@ Line 1,072: / Line 1,156: @@
 ====Subsequent treatment====
 *Non-progressors: [[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab consolidation]]
 *Responders: [[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab maintenance]] versus [[#Observation_3|observation]]
 ===References===
-# '''ML17638:''' Vitolo U, Ladetto M, Boccomini C, Baldini L, De Angelis F, Tucci A, Botto B, Chiappella A, Chiarenza A, Pinto A, De Renzo A, Zaja F, Castellino C, Bari A, Alvarez De Celis I, Evangelista A, Parvis G, Gamba E, Lobetti-Bodoni C, Ciccone G, Rossi G. Rituximab maintenance compared with observation after brief first-line R-FND chemoimmunotherapy with rituximab consolidation in patients age older than 60 years with advanced follicular lymphoma: a phase III randomized study by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Sep 20;31(27):3351-9. Epub 2013 Aug 19. [http://jco.ascopubs.org/content/31/27/3351.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23960180 PubMed]
+#'''ML17638:''' Vitolo U, Ladetto M, Boccomini C, Baldini L, De Angelis F, Tucci A, Botto B, Chiappella A, Chiarenza A, Pinto A, De Renzo A, Zaja F, Castellino C, Bari A, Alvarez De Celis I, Evangelista A, Parvis G, Gamba E, Lobetti-Bodoni C, Ciccone G, Rossi G. Rituximab maintenance compared with observation after brief first-line R-FND chemoimmunotherapy with rituximab consolidation in patients age older than 60 years with advanced follicular lymphoma: a phase III randomized study by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Sep 20;31(27):3351-9. Epub 2013 Aug 19. [http://jco.ascopubs.org/content/31/27/3351.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23960180 PubMed]
 <!-- This study was originally presented at the 2003 American Society of Clinical Oncology meeting and an update was presented at the 2014 American Society of Clinical Oncology meeting. -->
-# Nastoupil LJ, McLaughlin P, Feng L, Neelapu SS, Samaniego F, Hagemeister FB, Ayala A, Romaguera JE, Goy AH, Neal E, Wang M, Fayad L, Fanale MA, Oki Y, Westin JR, Rodriguez MA, Cabanillas F, Fowler NH. High ten-year remission rates following rituximab, fludarabine, mitoxantrone and dexamethasone (R-FND) with interferon maintenance in indolent lymphoma: results of a randomized study. Br J Haematol. 2017 Apr;177(2):263-270. Epub 2017 Mar 24. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.14541/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28340281 PubMed]
+#Nastoupil LJ, McLaughlin P, Feng L, Neelapu SS, Samaniego F, Hagemeister FB, Ayala A, Romaguera JE, Goy AH, Neal E, Wang M, Fayad L, Fanale MA, Oki Y, Westin JR, Rodriguez MA, Cabanillas F, Fowler NH. High ten-year remission rates following rituximab, fludarabine, mitoxantrone and dexamethasone (R-FND) with interferon maintenance in indolent lymphoma: results of a randomized study. Br J Haematol. 2017 Apr;177(2):263-270. Epub 2017 Mar 24. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.14541/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28340281 PubMed]
 ==R-MCP {{#subobject:2a4e31|Regimen=1}}==
@@ Line 1,089: / Line 1,175: @@
 ===Regimen {{#subobject:6fc8a3|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/25/15/1986.long Herold et al. 2007 (OSHO-39)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[Follicular_lymphoma_-_historical#MCP_.28Prednisolone.29|MCP]]
-|style="background-color:#1a9850"|Superior OS
+| style="background-color:#1a9850" |Superior OS
 |-
 |}
 ''Note: the chlorambucil dose is written in the reference as "3 x 3 mg/m<sup>2</sup>"; total dose per day is 9 mg/m<sup>2</sup>.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV once per day on days 3 & 4
@@ Line 1,109: / Line 1,196: @@
 '''28-day cycle for up to 8 cycles'''
 ====Subsequent treatment====
 *Patients who achieved a PR or CR: [[Follicular_lymphoma_-_historical#Interferon_alfa-2a_monotherapy|Interferon alfa-2a maintenance]] within 4 to 8 weeks of completion of chemotherapy
 ===References===
-# '''OSHO-39:''' Herold M, Haas A, Srock S, Neser S, Al-Ali KH, Neubauer A, Dölken G, Naumann R, Knauf W, Freund M, Rohrberg R, Höffken K, Franke A, Ittel T, Kettner E, Haak U, Mey U, Klinkenstein C, Assmann M, von Grünhagen U; East German Study Group Hematology and Oncology Study. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol. 2007 May 20;25(15):1986-92. Epub 2007 Apr 9. [http://jco.ascopubs.org/content/25/15/1986.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17420513 PubMed]
-## '''Update:''' Herold M, Scholz CW, Rothmann F, Hirt C, Lakner V, Naumann R. Long-term follow-up of rituximab plus first-line mitoxantrone, chlorambucil, prednisolone and interferon-alpha as maintenance therapy in follicular lymphoma. J Cancer Res Clin Oncol. 2015 Sep;141(9):1689-95. Epub 2015 Mar 25. [http://link.springer.com/article/10.1007/s00432-015-1963-9/fulltext.html link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25804839 PubMed]
+#'''OSHO-39:''' Herold M, Haas A, Srock S, Neser S, Al-Ali KH, Neubauer A, Dölken G, Naumann R, Knauf W, Freund M, Rohrberg R, Höffken K, Franke A, Ittel T, Kettner E, Haak U, Mey U, Klinkenstein C, Assmann M, von Grünhagen U; East German Study Group Hematology and Oncology Study. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol. 2007 May 20;25(15):1986-92. Epub 2007 Apr 9. [http://jco.ascopubs.org/content/25/15/1986.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17420513 PubMed]
+##'''Update:''' Herold M, Scholz CW, Rothmann F, Hirt C, Lakner V, Naumann R. Long-term follow-up of rituximab plus first-line mitoxantrone, chlorambucil, prednisolone and interferon-alpha as maintenance therapy in follicular lymphoma. J Cancer Res Clin Oncol. 2015 Sep;141(9):1689-95. Epub 2015 Mar 25. [http://link.springer.com/article/10.1007/s00432-015-1963-9/fulltext.html link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25804839 PubMed]
 ==Rituximab monotherapy {{#subobject:ea91fc|Regimen=1}}==
@@ Line 1,123: / Line 1,212: @@
 ===Variant #1, 4 doses {{#subobject:9ec4c2|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.bloodjournal.org/content/95/10/3052.long Hainsworth et al. 2000]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[http://www.bloodjournal.org/content/97/1/101.long Colombat et al. 2001]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[http://jco.ascopubs.org/content/20/20/4261.long Hainsworth et al. 2002]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[http://www.bloodjournal.org/content/103/12/4416.full Ghielmini et al. 2004 (SAKK 35/98)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
-|rowspan=2|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70027-0/abstract Ardeshna et al. 2014 (CRUK-2004-001621-16)]
+| rowspan="2" |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70027-0/abstract Ardeshna et al. 2014 (CRUK-2004-001621-16)]
-|rowspan=2 style="background-color:#1a9851"|Phase III (E-esc)
+| rowspan="2" style="background-color:#1a9851" |Phase III (E-esc)
 |1. [[#Observation_2|Observation]]
-|style="background-color:#1a9850"|Superior TTNT
+| style="background-color:#1a9850" |Superior TTNT
 |-
 |2. [[#Rituximab_monotherapy_2|Rituximab induction]], then [[#Rituximab_monotherapy.2C_extended_course|Rituximab maintenance]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of TTNT
+| style="background-color:#ffffbf" |Did not meet primary endpoint of TTNT
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171355/ Kahl et al. 2014 (RESORT)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872010/ Taverna et al. 2015 (SAKK 35/03)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(18)30157-1/fulltext Ogura et al. 2018 (CT-P10 3.4)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |CT-P10
-|style="background-color:#eeee01"|Equivalent ORR
+| style="background-color:#eeee01" |Equivalent ORR
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 ====Supportive medications====
 *[[Acetaminophen (Tylenol)]] 650 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to [[Rituximab (Rituxan)]]
 *[[Diphenhydramine (Benadryl)]] 50 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to [[Rituximab (Rituxan)]]
@@ Line 1,181: / Line 1,272: @@
 '''4-week course'''
 ====Subsequent treatment====
 *Hainsworth et al. 2002 & CT-P10 3.4, SD or better: [[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab maintenance]]
 *SAKK 35/98, SD or better: [[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab maintenance]] versus [[#Observation_3|no further treatment]]
@@ Line 1,188: / Line 1,280: @@
 ===Variant #2, 8 doses {{#subobject:bbfcca|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.tandfonline.com/doi/full/10.3109/10428194.2015.1014363 Kimby et al. 2015 (NLG ML16865)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |Rituximab & IFN-α2a
-|style="background-color:#ffffbf"|Did not meet primary endpoint of TTF
+| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
 |-
 |[http://www.bloodjournal.org/content/134/4/353.long Zucca et al. 2019 (SAKK 35/10)]
-|style="background-color:#1a9851"|Randomized Phase II (C)
+| style="background-color:#1a9851" |Randomized Phase II (C)
 |[[#Lenalidomide_.26_Rituximab|Lenalidomide & Rituximab]]
 | style="background-color:#fee08b" |Might have inferior CR/CRu rate
@@ Line 1,206: / Line 1,298: @@
 ''Note: only patients achieving some degree of measurable response in NLG ML16865 proceeded to the 2nd course of rituximab.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
@@ Line 1,211: / Line 1,304: @@
 ===References===
-# Hainsworth JD, Burris HA 3rd, Morrissey LH, Litchy S, Scullin DC Jr, Bearden JD 3rd, Richards P, Greco FA. Rituximab monoclonal antibody as initial systemic therapy for patients with low-grade non-Hodgkin lymphoma. Blood. 2000 May 15;95(10):3052-6. [http://www.bloodjournal.org/content/95/10/3052.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10807768 PubMed]
-# Colombat P, Salles G, Brousse N, Eftekhari P, Soubeyran P, Delwail V, Deconinck E, Haïoun C, Foussard C, Sebban C, Stamatoullas A, Milpied N, Boué F, Taillan B, Lederlin P, Najman A, Thièblemont C, Montestruc F, Mathieu-Boué A, Benzohra A, Solal-Céligny P. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation. Blood. 2001 Jan 1;97(1):101-6. [http://www.bloodjournal.org/content/97/1/101.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11133748 PubMed]
+#Hainsworth JD, Burris HA 3rd, Morrissey LH, Litchy S, Scullin DC Jr, Bearden JD 3rd, Richards P, Greco FA. Rituximab monoclonal antibody as initial systemic therapy for patients with low-grade non-Hodgkin lymphoma. Blood. 2000 May 15;95(10):3052-6. [http://www.bloodjournal.org/content/95/10/3052.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10807768 PubMed]
-## '''Update:''' Colombat P, Brousse N, Salles G, Morschhauser F, Brice P, Soubeyran P, Delwail V, Deconinck E, Haioun C, Foussard C, Sebban C, Tilly H, Thieblemont C, Bergougnoux L, Lazreg F, Solal-Celigny P. Rituximab induction immunotherapy for first-line low-tumor-burden follicular lymphoma: survival analyses with 7-year follow-up. Ann Oncol. 2012 Sep;23(9):2380-5. Epub 2012 Jul 10. [http://annonc.oxfordjournals.org/content/23/9/2380.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22782332 PubMed]
+#Colombat P, Salles G, Brousse N, Eftekhari P, Soubeyran P, Delwail V, Deconinck E, Haïoun C, Foussard C, Sebban C, Stamatoullas A, Milpied N, Boué F, Taillan B, Lederlin P, Najman A, Thièblemont C, Montestruc F, Mathieu-Boué A, Benzohra A, Solal-Céligny P. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation. Blood. 2001 Jan 1;97(1):101-6. [http://www.bloodjournal.org/content/97/1/101.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11133748 PubMed]
-# Hainsworth JD, Litchy S, Burris HA 3rd, Scullin DC Jr, Corso SW, Yardley DA, Morrissey L, Greco FA. Rituximab as first-line and maintenance therapy for patients with indolent non-hodgkin's lymphoma. J Clin Oncol. 2002 Oct 15;20(20):4261-7. [http://jco.ascopubs.org/content/20/20/4261.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12377971 PubMed]
+##'''Update:''' Colombat P, Brousse N, Salles G, Morschhauser F, Brice P, Soubeyran P, Delwail V, Deconinck E, Haioun C, Foussard C, Sebban C, Tilly H, Thieblemont C, Bergougnoux L, Lazreg F, Solal-Celigny P. Rituximab induction immunotherapy for first-line low-tumor-burden follicular lymphoma: survival analyses with 7-year follow-up. Ann Oncol. 2012 Sep;23(9):2380-5. Epub 2012 Jul 10. [http://annonc.oxfordjournals.org/content/23/9/2380.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22782332 PubMed]
-# '''SAKK 35/98:''' Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. [http://www.bloodjournal.org/content/103/12/4416.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14976046 PubMed]
+#Hainsworth JD, Litchy S, Burris HA 3rd, Scullin DC Jr, Corso SW, Yardley DA, Morrissey L, Greco FA. Rituximab as first-line and maintenance therapy for patients with indolent non-hodgkin's lymphoma. J Clin Oncol. 2002 Oct 15;20(20):4261-7. [http://jco.ascopubs.org/content/20/20/4261.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12377971 PubMed]
-## '''Update:''' Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. [http://jco.ascopubs.org/content/28/29/4480.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20697092 PubMed]
+#'''SAKK 35/98:''' Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. [http://www.bloodjournal.org/content/103/12/4416.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14976046 PubMed]
-# '''Meta-analysis:''' Vidal L, Gafter-Gvili A, Leibovici L, Dreyling M, Ghielmini M, Hsu Schmitz SF, Cohen A, Shpilberg O. Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials. J Natl Cancer Inst. 2009 Feb 18;101(4):248-55. Epub 2009 Feb 10. [https://www.ncbi.nlm.nih.gov/pubmed/19211444 PubMed]
+##'''Update:''' Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. [http://jco.ascopubs.org/content/28/29/4480.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20697092 PubMed]
-# '''CRUK-2004-001621-16:''' Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P, Warden J, Stevens L, Pocock CF, Miall F, Cunningham D, Davies J, Jack A, Stephens R, Walewski J, Ferhanoglu B, Bradstock K, Linch DC. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol. 2014 Apr;15(4):424-35. Epub 2014 Mar 4. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70027-0/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24602760 PubMed]
+#'''Meta-analysis:''' Vidal L, Gafter-Gvili A, Leibovici L, Dreyling M, Ghielmini M, Hsu Schmitz SF, Cohen A, Shpilberg O. Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials. J Natl Cancer Inst. 2009 Feb 18;101(4):248-55. Epub 2009 Feb 10. [https://www.ncbi.nlm.nih.gov/pubmed/19211444 PubMed]
-# '''ECOG E4402:''' Kahl BS, Hong F, Williams ME, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ. Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: Eastern Cooperative Oncology Group protocol E4402. J Clin Oncol. 2014 Oct 1;32(28):3096-102. Epub 2014 Aug 25. [http://jco.ascopubs.org/content/32/28/3096.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171355/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25154829 PubMed]
+#'''CRUK-2004-001621-16:''' Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P, Warden J, Stevens L, Pocock CF, Miall F, Cunningham D, Davies J, Jack A, Stephens R, Walewski J, Ferhanoglu B, Bradstock K, Linch DC. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol. 2014 Apr;15(4):424-35. Epub 2014 Mar 4. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70027-0/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24602760 PubMed]
+#'''ECOG E4402:''' Kahl BS, Hong F, Williams ME, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ. Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: Eastern Cooperative Oncology Group protocol E4402. J Clin Oncol. 2014 Oct 1;32(28):3096-102. Epub 2014 Aug 25. [http://jco.ascopubs.org/content/32/28/3096.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171355/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25154829 PubMed]
 <!-- # '''Abstract:''' Eva Kimby, Giovanni Martinelli, Bjorn Ostenstad, Ulrich JM Mey, Daniel Rauch, Björn E Wahlin, MD, PhD, Felicitas Hitz, MD, Micaela Hernberg, Ann-Sofie Johansson, Peter de Nully Brown, Hans Hagberg, Andrés J.M. Ferreri1, Andreas Lohri, Urban Novak, Thilo Zander, Hanne Bersvendsen, Mario Bargetzi, Walter Mingrone, Fatime Krasniqi, Stephan Dirnhofer, Hanne Hawle, MD, Simona Berardi, Steffi Demmel, Stephanie Rondeau and Emanuele Zucca, MD. Rituximab Plus Lenalidomide Improves the Complete Remission Rate in Comparison with Rituximab Monotherapy in Untreated Follicular Lymphoma Patients in Need of Therapy. Primary Endpoint Analysis of the Randomized Phase-2 Trial SAKK 35/10. ASH Annual Meeting 2014 Abstract 799 [http://www.bloodjournal.org/content/124/21/799 link to abstract] -->
-# '''SAKK 35/10:''' Zucca E, Rondeau S, Vanazzi A, Østenstad B, Mey UJM, Rauch D, Wahlin BE, Hitz F, Hernberg M, Johansson AS, de Nully Brown P, Hagberg H, Ferreri AJM, Lohri A, Novak U, Zander T, Bersvendsen H, Bargetzi M, Mingrone W, Krasniqi F, Dirnhofer S, Hayoz S, Hawle H, Vilei SB, Ghielmini M, Kimby E; Swiss Group for Clinical Cancer Research and the Nordic Lymphoma Group. Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy. Blood. 2019 Jul 25;134(4):353-362. Epub 2019 May 17. [http://www.bloodjournal.org/content/134/4/353.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/31101627 PubMed]
+#'''SAKK 35/10:''' Zucca E, Rondeau S, Vanazzi A, Østenstad B, Mey UJM, Rauch D, Wahlin BE, Hitz F, Hernberg M, Johansson AS, de Nully Brown P, Hagberg H, Ferreri AJM, Lohri A, Novak U, Zander T, Bersvendsen H, Bargetzi M, Mingrone W, Krasniqi F, Dirnhofer S, Hayoz S, Hawle H, Vilei SB, Ghielmini M, Kimby E; Swiss Group for Clinical Cancer Research and the Nordic Lymphoma Group. Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy. Blood. 2019 Jul 25;134(4):353-362. Epub 2019 May 17. [http://www.bloodjournal.org/content/134/4/353.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/31101627 PubMed]
-# '''NLG ML16865:''' Kimby E, Östenstad B, Brown P, Hagberg H, Erlanson M, Holte H, Linden O, Johansson AS, Ahlgren T, Wader K, Wahlin BE, Delabie J, Sundström C; Nordic Lymphoma Group (NLG). Two courses of four weekly infusions of rituximab with or without interferon-α2a: final results from a randomized phase III study in symptomatic indolent B-cell lymphomas. Leuk Lymphoma. 2015;56(9):2598-607. [http://www.tandfonline.com/doi/full/10.3109/10428194.2015.1014363 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25686644 PubMed]
+#'''NLG ML16865:''' Kimby E, Östenstad B, Brown P, Hagberg H, Erlanson M, Holte H, Linden O, Johansson AS, Ahlgren T, Wader K, Wahlin BE, Delabie J, Sundström C; Nordic Lymphoma Group (NLG). Two courses of four weekly infusions of rituximab with or without interferon-α2a: final results from a randomized phase III study in symptomatic indolent B-cell lymphomas. Leuk Lymphoma. 2015;56(9):2598-607. [http://www.tandfonline.com/doi/full/10.3109/10428194.2015.1014363 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25686644 PubMed]
-## '''Pooled Update:''' Lockmer S, Østenstad B, Hagberg H, Holte H, Johansson AS, Wahlin BE, Wader KF, Steen CB, Meyer P, Maisenhølder M, Smedby KE, Brown P, Kimby E. Chemotherapy-free initial treatment of advanced indolent lymphoma has durable effect with low toxicity: results from two Nordic Lymphoma Group trials with more than 10 years of follow-up. J Clin Oncol. 2018 Nov 20;36(33):3315-23. Epub 2018 Oct 4. [https://ascopubs.org/doi/full/10.1200/JCO.18.00262 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30285560 PubMed]
+##'''Pooled Update:''' Lockmer S, Østenstad B, Hagberg H, Holte H, Johansson AS, Wahlin BE, Wader KF, Steen CB, Meyer P, Maisenhølder M, Smedby KE, Brown P, Kimby E. Chemotherapy-free initial treatment of advanced indolent lymphoma has durable effect with low toxicity: results from two Nordic Lymphoma Group trials with more than 10 years of follow-up. J Clin Oncol. 2018 Nov 20;36(33):3315-23. Epub 2018 Oct 4. [https://ascopubs.org/doi/full/10.1200/JCO.18.00262 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30285560 PubMed]
 <!-- # '''Abstract:''' Taverna CJ, Bassi S, Hitz F, et al. Rituximab maintenance treatment for a maximum of 5 years in follicular lymphoma: Safety analysis of the randomized phase III trial SAKK 35/03 (Abstract 1802) Blood. 2010;116 [https://ash.confex.com/ash/2010/webprogram/Paper30282.html link to abstract]
 ## '''Abstract:''' '''Update:''' Christian J. Taverna, MD, Giovanni Martinelli, Felicitas Hitz, Walter Mingrone, Thomas Pabst, MD, Lidija Cevreska, Auro del Giglio, MD, Anna Vanazzi, Daniele Laszlo, Johann Raats, Daniel Rauch, Daniel A. Vorobiof, Andreas Lohri, MD, Emanuele Zucca, MD, Christine Biaggi Rudolf, Stephanie Rondeau, Corinne Rusterholz and Michele Ghielmini, MD. Rituximab Maintenance Treatment For a Maximum Of 5 Years In Follicular Lymphoma: Results Of The Randomized Phase III Trial SAKK 35/03. 2013 ASH Annual Meeting [https://ash.confex.com/ash/2013/webprogram/Paper61955.html link to abstract] -->
-# '''SAKK 35/03:''' Taverna C, Martinelli G, Hitz F, Mingrone W, Pabst T, Cevreska L, Del Giglio A, Vanazzi A, Laszlo D, Raats J, Rauch D, Vorobiof DA, Lohri A, Biaggi Rudolf C, Rondeau S, Rusterholz C, Heijnen IA, Zucca E, Ghielmini M. Rituximab maintenance for a maximum of 5 years after single-agent rituximab induction in follicular lymphoma: results of the randomized controlled phase III trial SAKK 35/03. J Clin Oncol. 2016 Feb 10;34(5):495-500. Epub 2015 Dec 28. [http://jco.ascopubs.org/content/34/5/495.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872010/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26712227 PubMed]
+#'''SAKK 35/03:''' Taverna C, Martinelli G, Hitz F, Mingrone W, Pabst T, Cevreska L, Del Giglio A, Vanazzi A, Laszlo D, Raats J, Rauch D, Vorobiof DA, Lohri A, Biaggi Rudolf C, Rondeau S, Rusterholz C, Heijnen IA, Zucca E, Ghielmini M. Rituximab maintenance for a maximum of 5 years after single-agent rituximab induction in follicular lymphoma: results of the randomized controlled phase III trial SAKK 35/03. J Clin Oncol. 2016 Feb 10;34(5):495-500. Epub 2015 Dec 28. [http://jco.ascopubs.org/content/34/5/495.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872010/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26712227 PubMed]
-# '''CT-P10 3.4:''' Ogura M, Sancho JM, Cho SG, Nakazawa H, Suzumiya J, Tumyan G, Kim JS, Lennard A, Mariz J, Ilyin N, Jurczak W, Lopez Martinez A, Samoilova O, Zhavrid E, Yañez Ruiz E, Trneny M, Popplewell L, Coiffier B, Buske C, Kim WS, Lee SJ, Lee SY, Bae YJ, Kwak LW. Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 in comparison with rituximab in patients with previously untreated low-tumour-burden follicular lymphoma: a randomised, double-blind, parallel-group, phase 3 trial. Lancet Haematol. 2018 Nov;5(11):e543-e553. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(18)30157-1/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30389036 PubMed]
+#'''CT-P10 3.4:''' Ogura M, Sancho JM, Cho SG, Nakazawa H, Suzumiya J, Tumyan G, Kim JS, Lennard A, Mariz J, Ilyin N, Jurczak W, Lopez Martinez A, Samoilova O, Zhavrid E, Yañez Ruiz E, Trneny M, Popplewell L, Coiffier B, Buske C, Kim WS, Lee SJ, Lee SY, Bae YJ, Kwak LW. Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 in comparison with rituximab in patients with previously untreated low-tumour-burden follicular lymphoma: a randomised, double-blind, parallel-group, phase 3 trial. Lancet Haematol. 2018 Nov;5(11):e543-e553. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(18)30157-1/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30389036 PubMed]
 =Advanced disease, first-line therapy, non-randomized or retrospective data=
@@ Line 1,239: / Line 1,333: @@
 ===Regimen {{#subobject:c1d64f|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://link.springer.com/article/10.1007%2Fs00277-014-2269-8 Czuczman et al. 2015 (C18083-2048)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''The subtypes of indolent lymphoma that this regimen was used for are not specified in the abstract. Given that follicular lymphoma is the most common indolent lymphoma, the regimen is included here.''
 ====Chemotherapy====
 *[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 *[[Ofatumumab (Arzerra)]] as follows:
@@ Line 1,257: / Line 1,352: @@
 ===References===
 <!-- Partial results were presented at the 53rd Annual Meeting of the American Society of Hematology, San Diego, CA on December 10–13, 2011. -->
-# '''C18083-2048:''' Czuczman MS, Kahanic S, Forero A, Davis G, Munteanu M, Van Den Neste E, Offner F, Bron D, Quick D, Fowler N. Results of a phase II study of bendamustine and ofatumumab in untreated indolent B cell non-Hodgkin's lymphoma. Ann Hematol. 2015 Apr;94(4):633-41. Epub 2015 Jan 30. [http://link.springer.com/article/10.1007%2Fs00277-014-2269-8 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25630297 PubMed]
+#'''C18083-2048:''' Czuczman MS, Kahanic S, Forero A, Davis G, Munteanu M, Van Den Neste E, Offner F, Bron D, Quick D, Fowler N. Results of a phase II study of bendamustine and ofatumumab in untreated indolent B cell non-Hodgkin's lymphoma. Ann Hematol. 2015 Apr;94(4):633-41. Epub 2015 Jan 30. [http://link.springer.com/article/10.1007%2Fs00277-014-2269-8 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25630297 PubMed]
 ==FR {{#subobject:263b57|Regimen=1}}==
@@ Line 1,267: / Line 1,363: @@
 ===Regimen {{#subobject:4f5008|Variant=1}}===
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/23/4/694.long Czuczman et al. 2005]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 | style="background-color:#f7fcfd" |ORR: 90%
 |-
 |}
 ====Chemotherapy====
 *[[Fludarabine (Fludara)]] as follows:
 **Weeks 2, 6, 10, 14, 18, 22: 25 mg/m<sup>2</sup> IV once per day on days 1 to 5
@@ Line 1,286: / Line 1,383: @@
 ===References===
-# Czuczman MS, Koryzna A, Mohr A, Stewart C, Donohue K, Blumenson L, Bernstein ZP, McCarthy P, Alam A, Hernandez-Ilizaliturri F, Skipper M, Brown K, Chanan-Khan A, Klippenstein D, Loud P, Rock MK, Benyunes M, Grillo-Lopez A, Bernstein SH. Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma. J Clin Oncol. 2005 Feb 1;23(4):694-704. [http://jco.ascopubs.org/content/23/4/694.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15681517 PubMed]
+#Czuczman MS, Koryzna A, Mohr A, Stewart C, Donohue K, Blumenson L, Bernstein ZP, McCarthy P, Alam A, Hernandez-Ilizaliturri F, Skipper M, Brown K, Chanan-Khan A, Klippenstein D, Loud P, Rock MK, Benyunes M, Grillo-Lopez A, Bernstein SH. Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma. J Clin Oncol. 2005 Feb 1;23(4):694-704. [http://jco.ascopubs.org/content/23/4/694.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15681517 PubMed]
 ==Ibritumomab tiuxetan monotherapy {{#subobject:37d27b|Regimen=1}}==
@@ Line 1,295: / Line 1,393: @@
 ===Variant #1 {{#subobject:9a590|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://jco.ascopubs.org/content/31/3/308.full Scholz et al. 2013]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.12695/full Ibatici et al. 2013]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 1,308: / Line 1,406: @@
 ''Recruitment in Scholz et al. was limited to patients at least 50 years old due to radiation safety concerns; Ibatici et al. was open to all adult patients greater than 18 years old. Treatment regimen is identical.''
 ====Radioimmunotherapy====
 *[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & either day 8 or 9, '''given first on day 8 or 9'''
-*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] 15 MBq/kg (maximum dose of 1200 MBq) IV once on day 8 or 9, '''given second'''
+*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 15 MBq/kg (maximum dose of 1200 MBq) IV once on day 8 or 9, '''given second'''
 '''8- to 9-day course'''
@@ Line 1,315: / Line 1,414: @@
 ===Variant #2, fractionated {{#subobject:5fd9ca|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://jco.ascopubs.org/content/32/3/212.full Illidge et al. 2013 (FIZZ)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''This regimen was for patients with less than or equal to 20% bone marrow involvement; others received induction rituximab, first. See paper for details.''
 ====Radioimmunotherapy====
 *[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on day 1 & either day 8 or 9, '''given first on day 8 or 9'''
-*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] 11.1 MBq/kg (maximum dose of 888 MBq) IV once on either day 8 or 9, '''given second'''
+*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 11.1 MBq/kg (maximum dose of 888 MBq) IV once on either day 8 or 9, '''given second'''
 '''8- to 12-week cycle for 2 cycles'''
@@ Line 1,331: / Line 1,431: @@
 ===References===
 <!-- Presented in part at the 52nd Annual Meeting of the American Society of Hematology, Orlando, FL, December 4–7, 2010. -->
-# Scholz CW, Pinto A, Linkesch W, Lindén O, Viardot A, Keller U, Hess G, Lastoria S, Lerch K, Frigeri F, Arcamone M, Stroux A, Frericks B, Pott C, Pezzutto A. 90Yttrium-ibritumomab-tiuxetan as first-line treatment for follicular lymphoma: 30 months of follow-up data from an international multicenter phase II clinical trial. J Clin Oncol. 2013 Jan 20;31(3):308-13. Epub 2012 Dec 10. [http://jco.ascopubs.org/content/31/3/308.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23233718 PubMed]
-# '''FIZZ:''' Illidge TM, Mayes S, Pettengell R, Bates AT, Bayne M, Radford JA, Ryder WD, Le Gouill S, Jardin F, Tipping J, Zivanovic M, Kraeber-Bodere F, Bardies M, Bodet-Milin C, Malek E, Huglo D, Morschhauser F. Fractionated 90Y-ibritumomab tiuxetan radioimmunotherapy as an initial therapy of follicular lymphoma: an international phase II study in patients requiring treatment according to GELF/BNLI criteria. J Clin Oncol. 2014 Jan 20;32(3):212-8. Epub 2013 Dec 2. [http://jco.ascopubs.org/content/32/3/212.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24297953 PubMed]
+#Scholz CW, Pinto A, Linkesch W, Lindén O, Viardot A, Keller U, Hess G, Lastoria S, Lerch K, Frigeri F, Arcamone M, Stroux A, Frericks B, Pott C, Pezzutto A. 90Yttrium-ibritumomab-tiuxetan as first-line treatment for follicular lymphoma: 30 months of follow-up data from an international multicenter phase II clinical trial. J Clin Oncol. 2013 Jan 20;31(3):308-13. Epub 2012 Dec 10. [http://jco.ascopubs.org/content/31/3/308.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23233718 PubMed]
-# Ibatici A, Pica GM, Nati S, Vitolo U, Botto B, Ciochetto C, Petrini M, Galimberti S, Ciabatti E, Orciuolo E, Zinzani PL, Cascavilla N, Guolo F, Fraternali Orcioni G, Carella AM. Safety and efficacy of (90) Yttrium-ibritumomab-tiuxetan for untreated follicular lymphoma patients: an Italian cooperative study. Br J Haematol. 2014 Mar;164(5):710-6. Epub 2013 Dec 17. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12695/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24344981 PubMed]
+#'''FIZZ:''' Illidge TM, Mayes S, Pettengell R, Bates AT, Bayne M, Radford JA, Ryder WD, Le Gouill S, Jardin F, Tipping J, Zivanovic M, Kraeber-Bodere F, Bardies M, Bodet-Milin C, Malek E, Huglo D, Morschhauser F. Fractionated 90Y-ibritumomab tiuxetan radioimmunotherapy as an initial therapy of follicular lymphoma: an international phase II study in patients requiring treatment according to GELF/BNLI criteria. J Clin Oncol. 2014 Jan 20;32(3):212-8. Epub 2013 Dec 2. [http://jco.ascopubs.org/content/32/3/212.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24297953 PubMed]
+#Ibatici A, Pica GM, Nati S, Vitolo U, Botto B, Ciochetto C, Petrini M, Galimberti S, Ciabatti E, Orciuolo E, Zinzani PL, Cascavilla N, Guolo F, Fraternali Orcioni G, Carella AM. Safety and efficacy of (90) Yttrium-ibritumomab-tiuxetan for untreated follicular lymphoma patients: an Italian cooperative study. Br J Haematol. 2014 Mar;164(5):710-6. Epub 2013 Dec 17. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12695/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24344981 PubMed]
 ==O-CHOP {{#subobject:a326e|Regimen=1}}==
@@ Line 1,344: / Line 1,445: @@
 ===Regimen {{#subobject:bcb2bf|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2012.09086.x/full Czuczman et al. 2012 (409 Study)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 1,354: / Line 1,455: @@
 ''Note: both 500 mg and 1000 mg doses of ofatumumab were tested, but since there was no increase in toxicity in patients receiving the 1000 mg dose, the 1000 mg dose was chosen for future ofatumumab trials "to avoid underdosing patients"''
 ====Chemotherapy====
 *[[Ofatumumab (Arzerra)]] as follows:
 **Cycle 1: 300 mg IV once on day 1
@@ Line 1,363: / Line 1,465: @@
 ====Supportive medications====
 *[[Acetaminophen (Tylenol)]] 1000 mg (no route specified) before each dose of [[Ofatumumab (Arzerra)]]
 *[[Cetirizine (Zyrtec)]] 10 mg (or equivalent) PO before each dose of [[Ofatumumab (Arzerra)]]
@@ Line 1,370: / Line 1,473: @@
 ===References===
-# Czuczman MS, Hess G, Gadeberg OV, Pedersen LM, Goldstein N, Gupta I, Jewell RC, Lin TS, Lisby S, Strange C, Windfeld K, Viardot A; 409 Study Investigators. Chemoimmunotherapy with ofatumumab in combination with CHOP in previously untreated follicular lymphoma. Br J Haematol. 2012 May;157(4):438-45. Epub 2012 Mar 13. [https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2012.09086.x/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22409295 PubMed]
+#Czuczman MS, Hess G, Gadeberg OV, Pedersen LM, Goldstein N, Gupta I, Jewell RC, Lin TS, Lisby S, Strange C, Windfeld K, Viardot A; 409 Study Investigators. Chemoimmunotherapy with ofatumumab in combination with CHOP in previously untreated follicular lymphoma. Br J Haematol. 2012 May;157(4):438-45. Epub 2012 Mar 13. [https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2012.09086.x/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22409295 PubMed]
 ==PCR {{#subobject:7b0b68|Regimen=1}}==
@@ Line 1,381: / Line 1,485: @@
 ===Regimen {{#subobject:91f7f7|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278955/ Samaniego et al. 2015 (MDACC 2004-0818)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Pentostatin (Nipent)]] 4 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,394: / Line 1,499: @@
 ====Supportive medications====
 *[[Ondansetron (Zofran)]] 8 mg (route not specified) prior to chemo
 *[[Diphenhydramine (Benadryl)]] 25 mg (route not specified) prior to chemo
@@ Line 1,405: / Line 1,511: @@
 ===References===
-# '''MDACC 2004-0818:''' Samaniego F, Hagemeister F, Romaguera JE, Fanale MA, Pro B, McLaughlin P, Rodriguez MA, Neelapu SS, Fayad L, Younes A, Feng L, Berkova Z, Khashab T, Sehgal L, Vega-Vasquez F, Kwak LW. Pentostatin, cyclophosphamide and rituximab for previously untreated advanced stage, low-grade B-cell lymphomas. Br J Haematol. 2015 Jun;169(6):814-23. Epub 2015 Mar 31. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13367/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278955/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25828695 PubMed]
-## '''Update:''' Khashab T, Hagemeister F, Romaguera JE, Fanale MA, Pro B, McLaughlin P, Rodriguez MA, Neelapu SS, Fayad L, Younes A, Feng L, Vega F, Kwak LW, Samaniego F. Long-term overall- and progression-free survival after pentostatin, cyclophosphamide and rituximab therapy for indolent non-Hodgkin lymphoma. Br J Haematol. 2019 May;185(4):670-678. Epub 2019 Feb 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.15814 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30820940 PubMed]
+#'''MDACC 2004-0818:''' Samaniego F, Hagemeister F, Romaguera JE, Fanale MA, Pro B, McLaughlin P, Rodriguez MA, Neelapu SS, Fayad L, Younes A, Feng L, Berkova Z, Khashab T, Sehgal L, Vega-Vasquez F, Kwak LW. Pentostatin, cyclophosphamide and rituximab for previously untreated advanced stage, low-grade B-cell lymphomas. Br J Haematol. 2015 Jun;169(6):814-23. Epub 2015 Mar 31. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13367/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278955/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25828695 PubMed]
+##'''Update:''' Khashab T, Hagemeister F, Romaguera JE, Fanale MA, Pro B, McLaughlin P, Rodriguez MA, Neelapu SS, Fayad L, Younes A, Feng L, Vega F, Kwak LW, Samaniego F. Long-term overall- and progression-free survival after pentostatin, cyclophosphamide and rituximab therapy for indolent non-Hodgkin lymphoma. Br J Haematol. 2019 May;185(4):670-678. Epub 2019 Feb 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.15814 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30820940 PubMed]
 ==R-CMD {{#subobject:965964|Regimen=1}}==
@@ Line 1,417: / Line 1,524: @@
 ===Regimen {{#subobject:5f88fb|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537487/ Sakai et al. 2015]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Note: the dose of dexamethasone in the manuscript text as well as the accompanying table is listed as 8 mg/body. It is unclear to us what this means.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cladribine (Leustatin)]] 0.10 mg/kg IV once per day on days 1 to 3
@@ Line 1,433: / Line 1,541: @@
 '''21-day cycle for 4 cycles'''
 ====Subsequent treatment====
 *[[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab consolidation]]
 ===References===
-# Sakai T, Masaki Y, Otsuki N, Sakamaki I, Kishi S, Miyazono T, Urasaki Y, Murakami J, Satoh T, Nakamura T, Iwao H, Nakajima A, Kawanami T, Miki M, Fujita Y, Tanaka M, Fukushima T, Okazaki T, Ueda T. Prospective clinical study of R-CMD therapy for indolent B cell lymphoma and mantle cell lymphoma from the Hokuriku Hematology Oncology Study Group. Med Oncol. 2015 Sep;32(9):232. '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537487/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26275804 PubMed]
+#Sakai T, Masaki Y, Otsuki N, Sakamaki I, Kishi S, Miyazono T, Urasaki Y, Murakami J, Satoh T, Nakamura T, Iwao H, Nakajima A, Kawanami T, Miki M, Fujita Y, Tanaka M, Fukushima T, Okazaki T, Ueda T. Prospective clinical study of R-CMD therapy for indolent B cell lymphoma and mantle cell lymphoma from the Hokuriku Hematology Oncology Study Group. Med Oncol. 2015 Sep;32(9):232. '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537487/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26275804 PubMed]
 ==R-FCM {{#subobject:79e50b|Regimen=1}}==
@@ Line 1,446: / Line 1,557: @@
 ===Regimen {{#subobject:4301c7|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2962175-7/fulltext Salles et al. 2010 (PRIMA)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows:
 **Cycles 1, 3, 5, 6: 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,463: / Line 1,575: @@
 '''28-day cycle for 6 cycles'''
 ====Subsequent treatment====
 *Responders (PR or CR): [[#Rituximab_monotherapy.2C_extended_course|Rituximab maintenance]] versus [[#Observation_3|no further treatment]]
 ===References===
-# '''PRIMA:''' Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2962175-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21176949 PubMed]
-## '''QoL Analysis:''' Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. [http://www.maneyonline.com/doi/full/10.1179/1607845414Y.0000000179 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25029908 PubMed]
+#'''PRIMA:''' Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2962175-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21176949 PubMed]
-## '''Update:''' Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. [https://ascopubs.org/doi/full/10.1200/JCO.19.01073 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823890/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/31339826 PubMed]
+##'''QoL Analysis:''' Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. [http://www.maneyonline.com/doi/full/10.1179/1607845414Y.0000000179 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25029908 PubMed]
+##'''Update:''' Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. [https://ascopubs.org/doi/full/10.1200/JCO.19.01073 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823890/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/31339826 PubMed]
 ==VR {{#subobject:f61648|Regimen=1}}==
@@ Line 1,478: / Line 1,592: @@
 ===Regimen {{#subobject:4ca454|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.12915/full Evens et al. 2014]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 *[[Rituximab (Rituxan)]] as follows:
@@ Line 1,493: / Line 1,608: @@
 '''35-day cycle for 3 cycles'''
 ====Subsequent treatment====
 *[[#VR_2|VR consolidation]]
 ===References===
-# Evens AM, Smith MR, Lossos IS, Helenowski I, Millenson M, Winter JN, Rosen ST, Gordon LI. Frontline bortezomib and rituximab for the treatment of newly diagnosed high tumour burden indolent non-hodgkin lymphoma: a multicentre phase II study. Br J Haematol. 2014 Aug;166(4):514-20. Epub 2014 Apr 25. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12915/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24761968 PubMed]
+#Evens AM, Smith MR, Lossos IS, Helenowski I, Millenson M, Winter JN, Rosen ST, Gordon LI. Frontline bortezomib and rituximab for the treatment of newly diagnosed high tumour burden indolent non-hodgkin lymphoma: a multicentre phase II study. Br J Haematol. 2014 Aug;166(4):514-20. Epub 2014 Apr 25. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12915/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24761968 PubMed]
 ==VR-CHOP {{#subobject:4ad713|Regimen=1}}==
@@ Line 1,507: / Line 1,624: @@
 ===Regimen {{#subobject:272810|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626332/ Cohen et al. 2015]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''The largest group of patients studied in this trial had follicular lymphoma. Note the decreased cap on vincristine.''
 ====Chemotherapy====
 *[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1 & 8
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,525: / Line 1,643: @@
 '''21-day cycle for up to 8 cycles'''
 ====Subsequent treatment====
 *Patients with CR: [[#Rituximab_monotherapy.2C_extended_course|Rituximab maintenance]]
 *Patients with SD/PR: [[#VR_3|VR maintenance]]
 ===References===
-# Cohen JB, Switchenko JM, Koff JL, Sinha R, Kaufman JL, Khoury HJ, Bumpers N, Colbert A, Hutchison-Rzepka A, Nastoupil LJ, Heffner LT, Langston AA, Lechowicz MJ, Lonial S, Flowers CR. A phase II study of bortezomib added to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients with previously untreated indolent non-Hodgkin's lymphoma. Br J Haematol. 2015 Nov;171(4):539-46. Epub 2015 Aug 7. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13637/full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626332/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26248505 PubMed]
+#Cohen JB, Switchenko JM, Koff JL, Sinha R, Kaufman JL, Khoury HJ, Bumpers N, Colbert A, Hutchison-Rzepka A, Nastoupil LJ, Heffner LT, Langston AA, Lechowicz MJ, Lonial S, Flowers CR. A phase II study of bortezomib added to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients with previously untreated indolent non-Hodgkin's lymphoma. Br J Haematol. 2015 Nov;171(4):539-46. Epub 2015 Aug 7. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13637/full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626332/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26248505 PubMed]
 =Consolidation after first-line therapy=
@@ Line 1,543: / Line 1,663: @@
 ===Variant #1 {{#subobject:f22c05|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/26/32/5156.long Morschhauser et al. 2008 (FIT)]
-|style="background-color:#1a9851"|Phase III (E-RT-esc)
+| style="background-color:#1a9851" |Phase III (E-RT-esc)
 |[[#Observation_3|Observation]]
-|style="background-color:#1a9850"|Superior PFS
+| style="background-color:#1a9850" |Superior PFS
 |-
 |}
 ====Preceding treatment====
 *First-line therapy (most received [[Follicular_lymphoma_-_historical#CHOP|CHOP]] or [[Follicular_lymphoma_-_historical#CVP|CVP]]; some received "CHOP-like", "rituximab combination", "fludarabine combination", or [[#Chlorambucil_monotherapy|chlorambucil]]), with PR/CR
 ====Radioimmunotherapy====
 *[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] 14.8 MBq/kg (maximum dose of 1184 MBq) IV over 10 minutes once on day 8, immediately following [[Rituximab (Rituxan)]]
+*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 14.8 MBq/kg (maximum dose of 1184 MBq) IV over 10 minutes once on day 8, immediately following [[Rituximab (Rituxan)]]
 '''8-day course'''
@@ Line 1,564: / Line 1,687: @@
 ===Variant #2 {{#subobject:27a6b8|Variant=1}}===
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[http://annonc.oxfordjournals.org/content/23/2/415.long Zinzani et al. 2011]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 | style="background-color:#f7fcfd" |ORR: 89%
 |-
 |}
 ====Preceding treatment====
 *[[#R-FM|FMR]]
 ====Radioimmunotherapy====
 *[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8 +/- 1 day (total dose: 500 mg/m<sup>2</sup>)
-*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] '''given immediately following second dose of rituximab''', as follows:
+*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] '''given immediately following second dose of rituximab''', as follows:
 **Platelet count greater than 150 x 10<sup>9</sup>/L: 14.8 MBq/kg (maximum dose of 1184 MBq) IV over 10 minutes once on day 8
 **Platelet count of 100 to 149 x 10<sup>9</sup>/L: 11.1 MBq/kg (maximum dose of 1184 MBq) IV over 10 minutes once on day 8
@@ Line 1,584: / Line 1,710: @@
 ===Variant #3 {{#subobject:6c2231|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.sciencedirect.com/science/article/pii/S1557919011701962 Hainsworth et al. 2009]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''See text for further information about Zevalin eligbility criteria. If patient did not meet criteria within 7 weeks after final R-CHOP, Zevalin was omitted.''
 ====Preceding treatment====
 *[[#R-CHOP|R-CHOP]] x 3
 ====Radioimmunotherapy====
-*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] 0.4 mCi/kg
+*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 0.4 mCi/kg
 **Dose reduced to 0.3 mCi/kg if platelet count 100 to 149 x 10<sup>9</sup>/L)
@@ Line 1,602: / Line 1,731: @@
 ===Variant #4 {{#subobject:b7a286|Variant=1}}===
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(08)70039-1/fulltext Zinzani et al. 2008 (FLUMIZ)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 | style="background-color:#f7fcfd" |ORR: 98%
 |-
 |}
 ====Preceding treatment====
 *[[Follicular_lymphoma_-_historical#FM|FM]]
 ====Radioimmunotherapy====
 *[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8 +/- 1 day (total dose: 500 mg/m<sup>2</sup>)
 *[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] '''given immediately following second dose of rituximab''', as follows:
@@ Line 1,623: / Line 1,755: @@
 ===Variant #5 {{#subobject:295662|Variant=1}}===
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[http://clincancerres.aacrjournals.org/content/14/21/7088.long Jacobs et al. 2008]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 | style="background-color:#f7fcfd" |ORR: 89%
 |-
 |}
 ====Preceding treatment====
 *[[#R-CHOP|R-CHOP]] x 3
 ====Radioimmunotherapy====
 *[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] 0.4 mCi/kg (15 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV over 10 minutes once on day 8, '''given immediately following rituximab'''
+*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 0.4 mCi/kg (15 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV over 10 minutes once on day 8, '''given immediately following rituximab'''
 '''8-day course, followed in 1 to 2 weeks by:'''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
@@ Line 1,647: / Line 1,783: @@
 ===Variant #6 {{#subobject:4c5004|Variant=1}}===
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[https://www.tandfonline.com/doi/full/10.3109/10428194.2013.790544 Provencio et al. 2013]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 | style="background-color:#f7fcfd" |ORR: 93%
 |-
@@ Line 1,658: / Line 1,794: @@
 ''To be completed; further details are not available in the abstract.''
 ====Preceding treatment====
-*[[#R-CHOP|R-CHOP]] x 4, then [[Follicular_lymphoma_-_historical#CHOP|CHOP]] x 2
+*[[#R-CHOP|R-CHOP]] x 4, then [[Follicular_lymphoma_-_historical#CHOP|CHOP]] x 2
 ====Radioimmunotherapy====
 *[[Ibritumomab tiuxetan (Zevalin)]]
 ===References===
-# '''FLUMIZ:''' Zinzani PL, Tani M, Pulsoni A, Gobbi M, Perotti A, De Luca S, Fabbri A, Zaccaria A, Voso MT, Fattori P, Guardigni L, Ronconi S, Cabras MG, Rigacci L, De Renzo A, Marchi E, Stefoni V, Fina M, Pellegrini C, Musuraca G, Derenzini E, Pileri S, Fanti S, Piccaluga PP, Baccarani M. Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase II non-randomised trial (FLUMIZ). Lancet Oncol. 2008 Apr;9(4):352-8. Epub 2008 Mar 14. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(08)70039-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18342572 PubMed]
-# '''FIT:''' Morschhauser F, Radford J, Van Hoof A, Vitolo U, Soubeyran P, Tilly H, Huijgens PC, Kolstad A, d'Amore F, Gonzalez Diaz M, Petrini M, Sebban C, Zinzani PL, van Oers MH, van Putten W, Bischof-Delaloye A, Rohatiner A, Salles G, Kuhlmann J, Hagenbeek A. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol. 2008 Nov 10;26(32):5156-64. Epub 2008 Oct 14. [http://jco.ascopubs.org/content/26/32/5156.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18854568 PubMed]
+#'''FLUMIZ:''' Zinzani PL, Tani M, Pulsoni A, Gobbi M, Perotti A, De Luca S, Fabbri A, Zaccaria A, Voso MT, Fattori P, Guardigni L, Ronconi S, Cabras MG, Rigacci L, De Renzo A, Marchi E, Stefoni V, Fina M, Pellegrini C, Musuraca G, Derenzini E, Pileri S, Fanti S, Piccaluga PP, Baccarani M. Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase II non-randomised trial (FLUMIZ). Lancet Oncol. 2008 Apr;9(4):352-8. Epub 2008 Mar 14. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(08)70039-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18342572 PubMed]
+#'''FIT:''' Morschhauser F, Radford J, Van Hoof A, Vitolo U, Soubeyran P, Tilly H, Huijgens PC, Kolstad A, d'Amore F, Gonzalez Diaz M, Petrini M, Sebban C, Zinzani PL, van Oers MH, van Putten W, Bischof-Delaloye A, Rohatiner A, Salles G, Kuhlmann J, Hagenbeek A. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol. 2008 Nov 10;26(32):5156-64. Epub 2008 Oct 14. [http://jco.ascopubs.org/content/26/32/5156.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18854568 PubMed]
 <!-- ## '''Update: Abstract:''' Hagenbeek, Anton, Radford, John, Van Hoof, Achiel, Vitolo, Umberto, Rohatiner, Ama Z.S., Salles, Gilles, Soubeyran, Pierre, Tilly, Herve, Delaloye, Angelika Bischof, van Putten, Wim L.J., Morschhauser, Franck. 90Y-Ibritumomab Tiuxetan (Zevalin(R)) Consolidation of First Remission In Advanced-Stage Follicular Non-Hodgkin's Lymphoma: Updated Results After a Median Follow-up of 66.2 Months From the International, Randomized, Phase III First-Line Indolent Trial (FIT) In 414 Patients. ASH Annual Meeting Abstracts 2010 116: 594 [http://abstracts.hematologylibrary.org/cgi/content/abstract/116/21/594 link to abstract]
 -->
-## '''Update:''' Morschhauser F, Radford J, Van Hoof A, Botto B, Rohatiner AZ, Salles G, Soubeyran P, Tilly H, Bischof-Delaloye A, van Putten WL, Kylstra JW, Hagenbeek A. 90Yttrium-ibritumomab tiuxetan consolidation of first remission in advanced-stage follicular non-Hodgkin lymphoma: updated results after a median follow-up of 7.3 years from the international, randomized, phase III First-Line Indolent Trial. J Clin Oncol. 2013 Jun 1;31(16):1977-83. Epub 2013 Apr 1. [http://jco.ascopubs.org/content/31/16/1977.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23547079 PubMed]
+##'''Update:''' Morschhauser F, Radford J, Van Hoof A, Botto B, Rohatiner AZ, Salles G, Soubeyran P, Tilly H, Bischof-Delaloye A, van Putten WL, Kylstra JW, Hagenbeek A. 90Yttrium-ibritumomab tiuxetan consolidation of first remission in advanced-stage follicular non-Hodgkin lymphoma: updated results after a median follow-up of 7.3 years from the international, randomized, phase III First-Line Indolent Trial. J Clin Oncol. 2013 Jun 1;31(16):1977-83. Epub 2013 Apr 1. [http://jco.ascopubs.org/content/31/16/1977.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23547079 PubMed]
-# Jacobs SA, Swerdlow SH, Kant J, Foon KA, Jankowitz R, Land SR, DeMonaco N, Joyce J, Osborn JL, Evans TL, Schaefer PM, Luong TM. Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Clin Cancer Res. 2008 Nov 1;14(21):7088-94. [http://clincancerres.aacrjournals.org/content/14/21/7088.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18981007 PubMed]
+#Jacobs SA, Swerdlow SH, Kant J, Foon KA, Jankowitz R, Land SR, DeMonaco N, Joyce J, Osborn JL, Evans TL, Schaefer PM, Luong TM. Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Clin Cancer Res. 2008 Nov 1;14(21):7088-94. [http://clincancerres.aacrjournals.org/content/14/21/7088.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18981007 PubMed]
-# Hainsworth JD, Spigel DR, Markus TM, Shipley D, Thompson D, Rotman R, Dannaher C, Greco FA. Rituximab plus short-duration chemotherapy followed by yttrium-90 ibritumomab tiuxetan as first-line treatment for patients with follicular non-Hodgkin lymphoma: a phase II trial of the Sarah Cannon Oncology Research Consortium. Clin Lymphoma Myeloma. 2009 Jun;9(3):223-8. [http://www.sciencedirect.com/science/article/pii/S1557919011701962 link to SD article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19525191 PubMed]
+#Hainsworth JD, Spigel DR, Markus TM, Shipley D, Thompson D, Rotman R, Dannaher C, Greco FA. Rituximab plus short-duration chemotherapy followed by yttrium-90 ibritumomab tiuxetan as first-line treatment for patients with follicular non-Hodgkin lymphoma: a phase II trial of the Sarah Cannon Oncology Research Consortium. Clin Lymphoma Myeloma. 2009 Jun;9(3):223-8. [http://www.sciencedirect.com/science/article/pii/S1557919011701962 link to SD article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19525191 PubMed]
-# Zinzani PL, Tani M, Pulsoni A, De Renzo A, Stefoni V, Broccoli A, Montini GC, Fina M, Pellegrini C, Gandolfi L, Cavalieri E, Torelli F, Scopinaro F, Argnani L, Quirini F, Derenzini E, Rossi M, Pileri S, Fanti S, Baccarani M. A phase II trial of short course fludarabine, mitoxantrone, rituximab followed by <sup>90</sup>Y-ibritumomab tiuxetan in untreated intermediate/high-risk follicular lymphoma. Ann Oncol. 2012 Feb;23(2):415-20. Epub 2011 May 2. [http://annonc.oxfordjournals.org/content/23/2/415.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21536660 PubMed]
+#Zinzani PL, Tani M, Pulsoni A, De Renzo A, Stefoni V, Broccoli A, Montini GC, Fina M, Pellegrini C, Gandolfi L, Cavalieri E, Torelli F, Scopinaro F, Argnani L, Quirini F, Derenzini E, Rossi M, Pileri S, Fanti S, Baccarani M. A phase II trial of short course fludarabine, mitoxantrone, rituximab followed by <sup>90</sup>Y-ibritumomab tiuxetan in untreated intermediate/high-risk follicular lymphoma. Ann Oncol. 2012 Feb;23(2):415-20. Epub 2011 May 2. [http://annonc.oxfordjournals.org/content/23/2/415.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21536660 PubMed]
-# Provencio M, Cruz Mora MÁ, Gómez-Codina J, Quero Blanco C, Llanos M, García-Arroyo FR, de la Cruz L, Gumá Padró J, Delgado Pérez JR, Sánchez A, Alvarez Cabellos R, Rueda A; Gotel (Spanish Lymphoma Oncology Group). Consolidation treatment with Yttrium-90 ibritumomab tiuxetan after new induction regimen in patients with intermediate- and high-risk follicular lymphoma according to the follicular lymphoma international prognostic index: a multicenter, prospective phase II trial of the Spanish Lymphoma Oncology Group. Leuk Lymphoma. 2014 Jan;55(1):51-5. Epub 2013 Jun 12. [https://www.tandfonline.com/doi/full/10.3109/10428194.2013.790544 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23573825 PubMed]
+#Provencio M, Cruz Mora MÁ, Gómez-Codina J, Quero Blanco C, Llanos M, García-Arroyo FR, de la Cruz L, Gumá Padró J, Delgado Pérez JR, Sánchez A, Alvarez Cabellos R, Rueda A; Gotel (Spanish Lymphoma Oncology Group). Consolidation treatment with Yttrium-90 ibritumomab tiuxetan after new induction regimen in patients with intermediate- and high-risk follicular lymphoma according to the follicular lymphoma international prognostic index: a multicenter, prospective phase II trial of the Spanish Lymphoma Oncology Group. Leuk Lymphoma. 2014 Jan;55(1):51-5. Epub 2013 Jun 12. [https://www.tandfonline.com/doi/full/10.3109/10428194.2013.790544 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23573825 PubMed]
-# '''Abstract:''' Armando Lopez-Guillermo, MD, PhD, Miguel A. Canales, MD, PhD, Ivan Dlouhy, Javier Briones, MD, Dolores Caballero, MD, PhD, Juan Manuel Sancho Sr., MD, Santiago Mercadal Vilchez, MD, Jose María Moraleda, MD, María José Terol, MD, PhD, Antonio Salar, MD, Luis Palomera, MD, Santiago Gardella, MD, Isidro Jarque, MD, Secundino Ferrer, Joan Bargay, MD, Andres Lopez, Carlos Panizo, Anna Muntanola, MD, Carlos Montalban, Eulogio Conde, MD, PhD, Miguel Hernandez, MD, Alfons Soler, Julian Marin, MD, Jose García Marco, Guillermo Deben and José Francisco Tomas, MD, PhD. A Randomized Phase II Study Comparing Consolidation With a Single Dose Of 90y Ibritumomab Tiuxetan (Zevalin®) (Z) Vs. Maintenance With Rituximab (R) For Two Years In Patients With Newly Diagnosed Follicular Lymphoma (FL) Responding To R-CHOP. Preliminary Results At 36 Months From Randomization. Blood 2013 122:369. [http://www.bloodjournal.org/content/122/21/369 link to abstract]
+#'''Abstract:''' Armando Lopez-Guillermo, MD, PhD, Miguel A. Canales, MD, PhD, Ivan Dlouhy, Javier Briones, MD, Dolores Caballero, MD, PhD, Juan Manuel Sancho Sr., MD, Santiago Mercadal Vilchez, MD, Jose María Moraleda, MD, María José Terol, MD, PhD, Antonio Salar, MD, Luis Palomera, MD, Santiago Gardella, MD, Isidro Jarque, MD, Secundino Ferrer, Joan Bargay, MD, Andres Lopez, Carlos Panizo, Anna Muntanola, MD, Carlos Montalban, Eulogio Conde, MD, PhD, Miguel Hernandez, MD, Alfons Soler, Julian Marin, MD, Jose García Marco, Guillermo Deben and José Francisco Tomas, MD, PhD. A Randomized Phase II Study Comparing Consolidation With a Single Dose Of 90y Ibritumomab Tiuxetan (Zevalin®) (Z) Vs. Maintenance With Rituximab (R) For Two Years In Patients With Newly Diagnosed Follicular Lymphoma (FL) Responding To R-CHOP. Preliminary Results At 36 Months From Randomization. Blood 2013 122:369. [http://www.bloodjournal.org/content/122/21/369 link to abstract]
 ==Observation==
@@ Line 1,680: / Line 1,821: @@
 ===Regimen===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://ascopubs.org/doi/abs/10.1200/JCO.1998.16.1.41 Hagenbeek et al. 1998]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |Interferon alfa
 | style="background-color:#fee08b" |Might have inferior TTP
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.2000.18.10.2010 Fisher et al. 2000 (SWOG S8809)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |Interferon alfa
-|style="background-color:#ffffbf"|Did not meet primary endpoints of PFS/OS
+| style="background-color:#ffffbf" |Did not meet primary endpoints of PFS/OS
 |-
 |[http://www.bloodjournal.org/content/103/12/4416.full Ghielmini et al. 2004 (SAKK 35/98)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab]]
-|style="background-color:#fc8d59"|Seems to have inferior EFS
+| style="background-color:#fc8d59" |Seems to have inferior EFS
 |-
 |[http://jco.ascopubs.org/content/26/32/5156.long Morschhauser et al. 2008 (FIT)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Ibritumomab_tiuxetan_monotherapy_3|Ibritumomab tiuxetan]]
-|style="background-color:#d73027"|Inferior PFS
+| style="background-color:#d73027" |Inferior PFS
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668968/ Hochster et al. 2009 (ECOG E1496)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Rituximab_monotherapy.2C_extended_course|Rituximab]]
-|style="background-color:#d73027"|Inferior PFS
+| style="background-color:#d73027" |Inferior PFS
 |-
 |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2962175-7/fulltext Salles et al. 2010 (PRIMA)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Rituximab_monotherapy.2C_extended_course|Rituximab]]
-|style="background-color:#d73027"|Inferior PFS
+| style="background-color:#d73027" |Inferior PFS
 |-
 |[http://jco.ascopubs.org/content/31/27/3351.full Vitolo et al. 2013 (ML17638)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 |-
 |}
 ''No further treatment after induction therapy.''
 ====Preceding treatment====
 *SAKK 35/98: [[#Rituximab_monotherapy_2|R]] x 4
 *FIT: First-line therapy (most received [[Follicular_lymphoma_-_historical#CHOP|CHOP]] or [[Follicular_lymphoma_-_historical#CVP|CVP]]; some received "CHOP-like", "rituximab combination", "fludarabine combination", or [[#Chlorambucil_monotherapy|chlorambucil]]), with PR/CR
@@ Line 1,730: / Line 1,872: @@
 ===References===
-# Hagenbeek A, Carde P, Meerwaldt JH, Somers R, Thomas J, De Bock R, Raemaekers JM, van Hoof A, De Wolf-Peeters C, van Glabbeke M; European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group. Maintenance of remission with human recombinant interferon alfa-2a in patients with stages III and IV low-grade malignant non-Hodgkin's lymphoma. J Clin Oncol. 1998 Jan;16(1):41-7. [https://ascopubs.org/doi/abs/10.1200/JCO.1998.16.1.41 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9440721 PubMed]
-# '''SWOG S8809:''' Fisher RI, Dana BW, LeBlanc M, Kjeldsberg C, Forman JD, Unger JM, Balcerzak SP, Gaynor ER, Roy V, Miller T. Interferon alpha consolidation after intensive chemotherapy does not prolong the progression-free survival of patients with low-grade non-Hodgkin's lymphoma: results of the Southwest Oncology Group randomized phase III study 8809. J Clin Oncol. 2000 May;18(10):2010-6. [https://ascopubs.org/doi/full/10.1200/JCO.2000.18.10.2010 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10811664 PubMed]
+#Hagenbeek A, Carde P, Meerwaldt JH, Somers R, Thomas J, De Bock R, Raemaekers JM, van Hoof A, De Wolf-Peeters C, van Glabbeke M; European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group. Maintenance of remission with human recombinant interferon alfa-2a in patients with stages III and IV low-grade malignant non-Hodgkin's lymphoma. J Clin Oncol. 1998 Jan;16(1):41-7. [https://ascopubs.org/doi/abs/10.1200/JCO.1998.16.1.41 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9440721 PubMed]
-# '''SAKK 35/98:''' Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. [http://www.bloodjournal.org/content/103/12/4416.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14976046 PubMed]
+#'''SWOG S8809:''' Fisher RI, Dana BW, LeBlanc M, Kjeldsberg C, Forman JD, Unger JM, Balcerzak SP, Gaynor ER, Roy V, Miller T. Interferon alpha consolidation after intensive chemotherapy does not prolong the progression-free survival of patients with low-grade non-Hodgkin's lymphoma: results of the Southwest Oncology Group randomized phase III study 8809. J Clin Oncol. 2000 May;18(10):2010-6. [https://ascopubs.org/doi/full/10.1200/JCO.2000.18.10.2010 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10811664 PubMed]
-## '''Update:''' Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. [http://jco.ascopubs.org/content/28/29/4480.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20697092 PubMed]
+#'''SAKK 35/98:''' Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. [http://www.bloodjournal.org/content/103/12/4416.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14976046 PubMed]
-# '''FIT:''' Morschhauser F, Radford J, Van Hoof A, Vitolo U, Soubeyran P, Tilly H, Huijgens PC, Kolstad A, d'Amore F, Gonzalez Diaz M, Petrini M, Sebban C, Zinzani PL, van Oers MH, van Putten W, Bischof-Delaloye A, Rohatiner A, Salles G, Kuhlmann J, Hagenbeek A. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol. 2008 Nov 10;26(32):5156-64. Epub 2008 Oct 14. [http://jco.ascopubs.org/content/26/32/5156.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18854568 PubMed]
+##'''Update:''' Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. [http://jco.ascopubs.org/content/28/29/4480.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20697092 PubMed]
+#'''FIT:''' Morschhauser F, Radford J, Van Hoof A, Vitolo U, Soubeyran P, Tilly H, Huijgens PC, Kolstad A, d'Amore F, Gonzalez Diaz M, Petrini M, Sebban C, Zinzani PL, van Oers MH, van Putten W, Bischof-Delaloye A, Rohatiner A, Salles G, Kuhlmann J, Hagenbeek A. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol. 2008 Nov 10;26(32):5156-64. Epub 2008 Oct 14. [http://jco.ascopubs.org/content/26/32/5156.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18854568 PubMed]
 <!-- ## '''Update:''' Hagenbeek, Anton, Radford, John, Van Hoof, Achiel, Vitolo, Umberto, Rohatiner, Ama Z.S., Salles, Gilles, Soubeyran, Pierre, Tilly, Herve, Delaloye, Angelika Bischof, van Putten, Wim L.J., Morschhauser, Franck. 90Y-Ibritumomab Tiuxetan (Zevalin(R)) Consolidation of First Remission In Advanced-Stage Follicular Non-Hodgkin's Lymphoma: Updated Results After a Median Follow-up of 66.2 Months From the International, Randomized, Phase III First-Line Indolent Trial (FIT) In 414 Patients. ASH Annual Meeting Abstracts 2010 116: 594 [http://abstracts.hematologylibrary.org/cgi/content/abstract/116/21/594 link to abstract] -->
-## '''Update:''' Morschhauser F, Radford J, Van Hoof A, Botto B, Rohatiner AZ, Salles G, Soubeyran P, Tilly H, Bischof-Delaloye A, van Putten WL, Kylstra JW, Hagenbeek A. 90Yttrium-ibritumomab tiuxetan consolidation of first remission in advanced-stage follicular non-Hodgkin lymphoma: updated results after a median follow-up of 7.3 years from the international, randomized, phase III First-Line Indolent Trial. J Clin Oncol. 2013 Jun 1;31(16):1977-83. Epub 2013 Apr 1. [http://jco.ascopubs.org/content/31/16/1977.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23547079 PubMed]
+##'''Update:''' Morschhauser F, Radford J, Van Hoof A, Botto B, Rohatiner AZ, Salles G, Soubeyran P, Tilly H, Bischof-Delaloye A, van Putten WL, Kylstra JW, Hagenbeek A. 90Yttrium-ibritumomab tiuxetan consolidation of first remission in advanced-stage follicular non-Hodgkin lymphoma: updated results after a median follow-up of 7.3 years from the international, randomized, phase III First-Line Indolent Trial. J Clin Oncol. 2013 Jun 1;31(16):1977-83. Epub 2013 Apr 1. [http://jco.ascopubs.org/content/31/16/1977.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23547079 PubMed]
 <!-- Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL, and the Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL. -->
-# '''ECOG E1496:''' Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. Epub 2009 Mar 2. [http://jco.ascopubs.org/content/27/10/1607.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668968/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19255334 PubMed]
+#'''ECOG E1496:''' Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. Epub 2009 Mar 2. [http://jco.ascopubs.org/content/27/10/1607.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668968/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19255334 PubMed]
-## '''Update:''' Barta SK, Li H, Hochster HS, Hong F, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Colocci N, Bengtson EM, Horning SJ, Kahl BS. Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496). Cancer. 2016 Oct;122(19):2996-3004. Epub 2016 Jun 28. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.30137/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030179/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27351685 PubMed]
+##'''Update:''' Barta SK, Li H, Hochster HS, Hong F, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Colocci N, Bengtson EM, Horning SJ, Kahl BS. Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496). Cancer. 2016 Oct;122(19):2996-3004. Epub 2016 Jun 28. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.30137/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030179/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27351685 PubMed]
-# '''PRIMA:''' Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2962175-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21176949 PubMed]
+#'''PRIMA:''' Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2962175-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21176949 PubMed]
-## '''QoL Analysis:''' Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. [http://www.maneyonline.com/doi/full/10.1179/1607845414Y.0000000179 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25029908 PubMed]
+##'''QoL Analysis:''' Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. [http://www.maneyonline.com/doi/full/10.1179/1607845414Y.0000000179 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25029908 PubMed]
-## '''Update:''' Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. [https://ascopubs.org/doi/full/10.1200/JCO.19.01073 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823890/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/31339826 PubMed]
+##'''Update:''' Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. [https://ascopubs.org/doi/full/10.1200/JCO.19.01073 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823890/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/31339826 PubMed]
 <!-- Presented in part at the American Society of Hematology Annual Meeting, December 10-13, 2011, San Diego, CA. -->
-# '''ML17638:''' Vitolo U, Ladetto M, Boccomini C, Baldini L, De Angelis F, Tucci A, Botto B, Chiappella A, Chiarenza A, Pinto A, De Renzo A, Zaja F, Castellino C, Bari A, Alvarez De Celis I, Evangelista A, Parvis G, Gamba E, Lobetti-Bodoni C, Ciccone G, Rossi G. Rituximab maintenance compared with observation after brief first-line R-FND chemoimmunotherapy with rituximab consolidation in patients age older than 60 years with advanced follicular lymphoma: a phase III randomized study by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Sep 20;31(27):3351-9. Epub 2013 Aug 19. [http://jco.ascopubs.org/content/31/27/3351.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23960180 PubMed]
+#'''ML17638:''' Vitolo U, Ladetto M, Boccomini C, Baldini L, De Angelis F, Tucci A, Botto B, Chiappella A, Chiarenza A, Pinto A, De Renzo A, Zaja F, Castellino C, Bari A, Alvarez De Celis I, Evangelista A, Parvis G, Gamba E, Lobetti-Bodoni C, Ciccone G, Rossi G. Rituximab maintenance compared with observation after brief first-line R-FND chemoimmunotherapy with rituximab consolidation in patients age older than 60 years with advanced follicular lymphoma: a phase III randomized study by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Sep 20;31(27):3351-9. Epub 2013 Aug 19. [http://jco.ascopubs.org/content/31/27/3351.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23960180 PubMed]
 ==Rituximab monotherapy, abbreviated course {{#subobject:87e6f7|Regimen=1}}==
@@ Line 1,754: / Line 1,897: @@
 ===Variant #1, 2 doses in 2 weeks {{#subobject:8a54ec|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://jco.ascopubs.org/content/23/7/1500.long Hainsworth et al. 2005a]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Counting from the beginning, this is given in weeks 14 & 15.''
 ====Preceding treatment====
 *[[#Rituximab_monotherapy|Rituximab pre-phase]] x 4, then [[#R-CHOP|R-CHOP]] x 3
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1 & 8
@@ Line 1,771: / Line 1,917: @@
 ===Variant #2, 4 doses in 4 weeks {{#subobject:492bdc|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.bloodjournal.org/content/99/3/856.long Rambaldi et al. 2002]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |[http://jco.ascopubs.org/content/20/20/4261.long Hainsworth et al. 2002]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |[http://www.bloodjournal.org/content/111/8/4004.long Ladetto et al. 2008]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
 ====Preceding treatment====
 *Rambaldi et al. 2002 & Ladetto et al. 2008: [[Follicular_lymphoma_-_historical#CHOP|CHOP]] x 6
 *Hainsworth et al. 2002: [[#Rituximab_monotherapy_2|Rituximab]]
 *Zinzani et al. 2004: [[Follicular_lymphoma_-_historical#CHOP|CHOP]] x 6 versus [[Follicular_lymphoma_-_historical#FM|FM]] x 6
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 ====Supportive medications====
 *[[Acetaminophen (Tylenol)]] 650 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to [[Rituximab (Rituxan)]]
 *[[Diphenhydramine (Benadryl)]] 50 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to [[Rituximab (Rituxan)]]
@@ Line 1,799: / Line 1,949: @@
 ===Variant #3, 4 doses in 4 months {{#subobject:ae2fcf|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537487/ Sakai et al. 2015]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Preceding treatment====
 *[[#R-CMD|R-CMD]] x 4
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,815: / Line 1,968: @@
 ===Variant #4, 8 doses in 8 months {{#subobject:d4dff2|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/31/27/3351.full Vitolo et al. 2013 (ML17638)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#Observation_3|Observation]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 |-
 |}
 ====Preceding treatment====
 *[[#R-FND|R-FND]]
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,835: / Line 1,991: @@
 ===Variant #5, 8 doses in 9 months {{#subobject:965d6b|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.bloodjournal.org/content/103/12/4416.full Ghielmini et al. 2004 (SAKK 35/98)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#Observation_3|Observation]]
-|style="background-color:#91cf60"|Seems to have superior EFS
+| style="background-color:#91cf60" |Seems to have superior EFS
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872010/ Taverna et al. 2015 (SAKK 35/03)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Rituximab_monotherapy.2C_very_extended_course|Rituximab]] x 5 y
-|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 |-
 |}
 ''Note: maintenance treatment begins in week 12.''
 ====Preceding treatment====
 *[[#Rituximab_monotherapy_2|Rituximab]]
 ====Chemotherapy====
-*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 '''2-month cycle for 4 cycles'''
 ===References===
-# Rambaldi A, Lazzari M, Manzoni C, Carlotti E, Arcaini L, Baccarani M, Barbui T, Bernasconi C, Dastoli G, Fuga G, Gamba E, Gargantini L, Gattei V, Lauria F, Lazzarino M, Mandelli F, Morra E, Pulsoni A, Ribersani M, Rossi-Ferrini PL, Rupolo M, Tura S, Zagonel V, Zaja F, Zinzani P, Reato G, Foa R. Monitoring of minimal residual disease after CHOP and rituximab in previously untreated patients with follicular lymphoma. Blood. 2002 Feb 1;99(3):856-62. [http://www.bloodjournal.org/content/99/3/856.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11806987 PubMed]
-# Hainsworth JD, Litchy S, Burris HA 3rd, Scullin DC Jr, Corso SW, Yardley DA, Morrissey L, Greco FA. Rituximab as first-line and maintenance therapy for patients with indolent non-hodgkin's lymphoma. J Clin Oncol. 2002 Oct 15;20(20):4261-7. [http://jco.ascopubs.org/content/20/20/4261.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12377971 PubMed]
+#Rambaldi A, Lazzari M, Manzoni C, Carlotti E, Arcaini L, Baccarani M, Barbui T, Bernasconi C, Dastoli G, Fuga G, Gamba E, Gargantini L, Gattei V, Lauria F, Lazzarino M, Mandelli F, Morra E, Pulsoni A, Ribersani M, Rossi-Ferrini PL, Rupolo M, Tura S, Zagonel V, Zaja F, Zinzani P, Reato G, Foa R. Monitoring of minimal residual disease after CHOP and rituximab in previously untreated patients with follicular lymphoma. Blood. 2002 Feb 1;99(3):856-62. [http://www.bloodjournal.org/content/99/3/856.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11806987 PubMed]
-# '''SAKK 35/98:''' Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. [http://www.bloodjournal.org/content/103/12/4416.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14976046 PubMed]
+#Hainsworth JD, Litchy S, Burris HA 3rd, Scullin DC Jr, Corso SW, Yardley DA, Morrissey L, Greco FA. Rituximab as first-line and maintenance therapy for patients with indolent non-hodgkin's lymphoma. J Clin Oncol. 2002 Oct 15;20(20):4261-7. [http://jco.ascopubs.org/content/20/20/4261.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12377971 PubMed]
-## '''Update:''' Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. [http://jco.ascopubs.org/content/28/29/4480.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20697092 PubMed]
+#'''SAKK 35/98:''' Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. [http://www.bloodjournal.org/content/103/12/4416.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14976046 PubMed]
-# Hainsworth JD, Litchy S, Morrissey LH, Andrews MB, Grimaldi M, McCarty M, Greco FA. Rituximab plus short-duration chemotherapy as first-line treatment for follicular non-Hodgkin's lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Mar 1;23(7):1500-6. Epub 2005 Jan 4. [http://jco.ascopubs.org/content/23/7/1500.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15632411 PubMed]
+##'''Update:''' Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. [http://jco.ascopubs.org/content/28/29/4480.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20697092 PubMed]
-# Ladetto M, De Marco F, Benedetti F, Vitolo U, Patti C, Rambaldi A, Pulsoni A, Musso M, Liberati AM, Olivieri A, Gallamini A, Pogliani E, Rota Scalabrini D, Callea V, Di Raimondo F, Pavone V, Tucci A, Cortelazzo S, Levis A, Boccadoro M, Majolino I, Pileri A, Gianni AM, Passera R, Corradini P, Tarella C; Gruppo Italiano Trapianto di Midollo Osseo (GITMO); Intergruppo Italiano Linfomi (IIL). Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage. Blood. 2008 Apr 15;111(8):4004-13. Epub 2008 Jan 31. [http://www.bloodjournal.org/content/111/8/4004.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18239086 PubMed]
+#Hainsworth JD, Litchy S, Morrissey LH, Andrews MB, Grimaldi M, McCarty M, Greco FA. Rituximab plus short-duration chemotherapy as first-line treatment for follicular non-Hodgkin's lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Mar 1;23(7):1500-6. Epub 2005 Jan 4. [http://jco.ascopubs.org/content/23/7/1500.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15632411 PubMed]
+#Ladetto M, De Marco F, Benedetti F, Vitolo U, Patti C, Rambaldi A, Pulsoni A, Musso M, Liberati AM, Olivieri A, Gallamini A, Pogliani E, Rota Scalabrini D, Callea V, Di Raimondo F, Pavone V, Tucci A, Cortelazzo S, Levis A, Boccadoro M, Majolino I, Pileri A, Gianni AM, Passera R, Corradini P, Tarella C; Gruppo Italiano Trapianto di Midollo Osseo (GITMO); Intergruppo Italiano Linfomi (IIL). Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage. Blood. 2008 Apr 15;111(8):4004-13. Epub 2008 Jan 31. [http://www.bloodjournal.org/content/111/8/4004.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18239086 PubMed]
 <!-- Presented in part at the American Society of Hematology Annual Meeting, December 10-13, 2011, San Diego, CA. -->
-# '''ML17638:''' Vitolo U, Ladetto M, Boccomini C, Baldini L, De Angelis F, Tucci A, Botto B, Chiappella A, Chiarenza A, Pinto A, De Renzo A, Zaja F, Castellino C, Bari A, Alvarez De Celis I, Evangelista A, Parvis G, Gamba E, Lobetti-Bodoni C, Ciccone G, Rossi G. Rituximab maintenance compared with observation after brief first-line R-FND chemoimmunotherapy with rituximab consolidation in patients age older than 60 years with advanced follicular lymphoma: a phase III randomized study by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Sep 20;31(27):3351-9. Epub 2013 Aug 19. [http://jco.ascopubs.org/content/31/27/3351.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23960180 PubMed]
+#'''ML17638:''' Vitolo U, Ladetto M, Boccomini C, Baldini L, De Angelis F, Tucci A, Botto B, Chiappella A, Chiarenza A, Pinto A, De Renzo A, Zaja F, Castellino C, Bari A, Alvarez De Celis I, Evangelista A, Parvis G, Gamba E, Lobetti-Bodoni C, Ciccone G, Rossi G. Rituximab maintenance compared with observation after brief first-line R-FND chemoimmunotherapy with rituximab consolidation in patients age older than 60 years with advanced follicular lymphoma: a phase III randomized study by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Sep 20;31(27):3351-9. Epub 2013 Aug 19. [http://jco.ascopubs.org/content/31/27/3351.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23960180 PubMed]
-# Sakai T, Masaki Y, Otsuki N, Sakamaki I, Kishi S, Miyazono T, Urasaki Y, Murakami J, Satoh T, Nakamura T, Iwao H, Nakajima A, Kawanami T, Miki M, Fujita Y, Tanaka M, Fukushima T, Okazaki T, Ueda T. Prospective clinical study of R-CMD therapy for indolent B cell lymphoma and mantle cell lymphoma from the Hokuriku Hematology Oncology Study Group. Med Oncol. 2015 Sep;32(9):232. '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537487/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26275804 PubMed]
+#Sakai T, Masaki Y, Otsuki N, Sakamaki I, Kishi S, Miyazono T, Urasaki Y, Murakami J, Satoh T, Nakamura T, Iwao H, Nakajima A, Kawanami T, Miki M, Fujita Y, Tanaka M, Fukushima T, Okazaki T, Ueda T. Prospective clinical study of R-CMD therapy for indolent B cell lymphoma and mantle cell lymphoma from the Hokuriku Hematology Oncology Study Group. Med Oncol. 2015 Sep;32(9):232. '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537487/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26275804 PubMed]
 <!-- # '''Abstract:''' Taverna CJ, Bassi S, Hitz F, et al. Rituximab maintenance treatment for a maximum of 5 years in follicular lymphoma: Safety analysis of the randomized phase III trial SAKK 35/03 (Abstract 1802) Blood. 2010;116 [https://ash.confex.com/ash/2010/webprogram/Paper30282.html link to abstract]
 ## '''Abstract:''' '''Update:''' Christian J. Taverna, MD, Giovanni Martinelli, Felicitas Hitz, Walter Mingrone, Thomas Pabst, MD, Lidija Cevreska, Auro del Giglio, MD, Anna Vanazzi, Daniele Laszlo, Johann Raats, Daniel Rauch, Daniel A. Vorobiof, Andreas Lohri, MD, Emanuele Zucca, MD, Christine Biaggi Rudolf, Stephanie Rondeau, Corinne Rusterholz and Michele Ghielmini, MD. Rituximab Maintenance Treatment For a Maximum Of 5 Years In Follicular Lymphoma: Results Of The Randomized Phase III Trial SAKK 35/03. 2013 ASH Annual Meeting [https://ash.confex.com/ash/2013/webprogram/Paper61955.html link to abstract] -->
-# '''SAKK 35/03:''' Taverna C, Martinelli G, Hitz F, Mingrone W, Pabst T, Cevreska L, Del Giglio A, Vanazzi A, Laszlo D, Raats J, Rauch D, Vorobiof DA, Lohri A, Biaggi Rudolf C, Rondeau S, Rusterholz C, Heijnen IA, Zucca E, Ghielmini M. Rituximab maintenance for a maximum of 5 years after single-agent rituximab induction in follicular lymphoma: results of the randomized controlled phase III trial SAKK 35/03. J Clin Oncol. 2016 Feb 10;34(5):495-500. Epub 2015 Dec 28. [http://jco.ascopubs.org/content/34/5/495.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872010/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26712227 PubMed]
+#'''SAKK 35/03:''' Taverna C, Martinelli G, Hitz F, Mingrone W, Pabst T, Cevreska L, Del Giglio A, Vanazzi A, Laszlo D, Raats J, Rauch D, Vorobiof DA, Lohri A, Biaggi Rudolf C, Rondeau S, Rusterholz C, Heijnen IA, Zucca E, Ghielmini M. Rituximab maintenance for a maximum of 5 years after single-agent rituximab induction in follicular lymphoma: results of the randomized controlled phase III trial SAKK 35/03. J Clin Oncol. 2016 Feb 10;34(5):495-500. Epub 2015 Dec 28. [http://jco.ascopubs.org/content/34/5/495.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872010/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26712227 PubMed]
 ==VR {{#subobject:0ffdd4|Regimen=1}}==
@@ Line 1,881: / Line 2,041: @@
 ===Regimen {{#subobject:9e7df2|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.12915/full Evens et al. 2014]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Preceding treatment====
 *[[#VR|VR induction]]
 ====Chemotherapy====
 *[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once on day 1
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,897: / Line 2,060: @@
 ===References===
-# Evens AM, Smith MR, Lossos IS, Helenowski I, Millenson M, Winter JN, Rosen ST, Gordon LI. Frontline bortezomib and rituximab for the treatment of newly diagnosed high tumour burden indolent non-hodgkin lymphoma: a multicentre phase II study. Br J Haematol. 2014 Aug;166(4):514-20. Epub 2014 Apr 25. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12915/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24761968 PubMed]
+#Evens AM, Smith MR, Lossos IS, Helenowski I, Millenson M, Winter JN, Rosen ST, Gordon LI. Frontline bortezomib and rituximab for the treatment of newly diagnosed high tumour burden indolent non-hodgkin lymphoma: a multicentre phase II study. Br J Haematol. 2014 Aug;166(4):514-20. Epub 2014 Apr 25. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12915/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24761968 PubMed]
 =Maintenance after first-line therapy=
@@ Line 1,909: / Line 2,073: @@
 ===Regimen {{#subobject:e008ef|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.nejm.org/doi/full/10.1056/NEJMoa1805104 Morschhauser et al. 2018 (RELEVANCE)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
 ====Preceding treatment====
 *[[#Lenalidomide_.26_Rituximab|Lenalidomide & Rituximab induction]]
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 10 mg PO once per day
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,925: / Line 2,092: @@
 ===References===
-# '''RELEVANCE:''' Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. [https://www.nejm.org/doi/full/10.1056/NEJMoa1805104 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30184451 PubMed]
+#'''RELEVANCE:''' Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. [https://www.nejm.org/doi/full/10.1056/NEJMoa1805104 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30184451 PubMed]
 ==Obinutuzumab monotherapy {{#subobject:8dda05|Regimen=1}}==
@@ Line 1,934: / Line 2,102: @@
 ===Regimen {{#subobject:41d568|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[https://www.nejm.org/doi/10.1056/NEJMoa1614598 Marcus et al. 2017 (GALLIUM)]
@@ Line 1,944: / Line 2,112: @@
 |[[Complex_multipart_regimens#GALLIUM|See link]]
 | style="background-color:#1a9850" |[[Complex_multipart_regimens#GALLIUM|See link]]
-| style="background-color:#1a9850" | style="background-color:#d73027" |[[Complex_multipart_regimens#GALLIUM|See link]]
+| style="background-color:#1a9850" |<nowiki>style="background-color:#d73027" |</nowiki>[[Complex_multipart_regimens#GALLIUM|See link]]
 |-
 |}
 ====Preceding treatment====
 *[[#Bendamustine_.26_Obinutuzumab|G-B]] x 6 or [[#G-CHOP|G-CHOP]] x 6 or [[#G-CVP|G-CVP]] x 6
 ====Chemotherapy====
 *[[Obinutuzumab (Gazyva)]] 1000 mg IV once on day 1
 '''2-month cycle for 12 cycles'''
 ===References===
-# '''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://www.nejm.org/doi/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains verified protocol in appendix''' [https://www.ncbi.nlm.nih.gov/pubmed/28976863 PubMed]
-## '''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8960 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29856692 PubMed]
+#'''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://www.nejm.org/doi/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains verified protocol in appendix''' [https://www.ncbi.nlm.nih.gov/pubmed/28976863 PubMed]
+##'''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8960 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29856692 PubMed]
 ==Placebo==
@@ Line 1,964: / Line 2,136: @@
 ===Regimen===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646306/ Freedman et al. 2009]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |Mitumprotimut-T & GM-CSF
 | style="background-color:#91cf60" |Seems to have superior TTP
@@ Line 1,977: / Line 2,149: @@
 ''No active antineoplastic treatment.''
 ====Preceding treatment====
 *[[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab]] x 4
 ===References===
-# Freedman A, Neelapu SS, Nichols C, Robertson MJ, Djulbegovic B, Winter JN, Bender JF, Gold DP, Ghalie RG, Stewart ME, Esquibel V, Hamlin P. Placebo-controlled phase III trial of patient-specific immunotherapy with mitumprotimut-T and granulocyte-macrophage colony-stimulating factor after rituximab in patients with follicular lymphoma. J Clin Oncol. 2009 Jun 20;27(18):3036-43. Epub 2009 May 4. [https://ascopubs.org/doi/full/10.1200/JCO.2008.19.8903 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646306/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19414675 PubMed]
+#Freedman A, Neelapu SS, Nichols C, Robertson MJ, Djulbegovic B, Winter JN, Bender JF, Gold DP, Ghalie RG, Stewart ME, Esquibel V, Hamlin P. Placebo-controlled phase III trial of patient-specific immunotherapy with mitumprotimut-T and granulocyte-macrophage colony-stimulating factor after rituximab in patients with follicular lymphoma. J Clin Oncol. 2009 Jun 20;27(18):3036-43. Epub 2009 May 4. [https://ascopubs.org/doi/full/10.1200/JCO.2008.19.8903 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646306/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19414675 PubMed]
 ==Rituximab monotherapy, extended course {{#subobject:e26b69|Regimen=1}}==
@@ Line 1,990: / Line 2,164: @@
 ===Variant #1, q8wk cycles {{#subobject:4c0082|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2962175-7/fulltext Salles et al. 2010 (PRIMA)]
-|style="background-color:#1a9851"|Phase III (E-RT-esc)
+| style="background-color:#1a9851" |Phase III (E-RT-esc)
 |[[#Observation_3|Observation]]
-|style="background-color:#1a9850"|Superior PFS
+| style="background-color:#1a9850" |Superior PFS
 |-
 |[https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(17)30078-9/fulltext Davies et al. 2017 (SABRINA)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Rituximab_monotherapy.2C_extended_course|SC Rituximab]]
 | style="background-color:#ffffbf" |Similar efficacy
@@ Line 2,008: / Line 2,182: @@
 ''Starts 8 weeks after the last induction treatment.''
 ====Preceding treatment====
 *PRIMA: [[#R-CHOP|R-CHOP]] or [[#R-CVP|R-CVP]] or [[#R-FCM|R-FCM]]
 *SABRINA: [[#R-CHOP|R-CHOP]] or [[#R-CVP|R-CVP]]
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 2,017: / Line 2,194: @@
 ===Variant #2, q6mo cycles {{#subobject:ae8823|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668968/ Hochster et al. 2009 (ECOG E1496)]
-|style="background-color:#1a9851"|Phase III (E-RT-esc)
+| style="background-color:#1a9851" |Phase III (E-RT-esc)
 |[[#Observation_3|Observation]]
-|style="background-color:#1a9850"|Superior PFS
+| style="background-color:#1a9850" |Superior PFS
 |-
 |}
 ====Preceding treatment====
 *[[Follicular_lymphoma_-_historical#CVP|CVP]] x 6 to 8 cycles
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
@@ Line 2,037: / Line 2,217: @@
 ===Variant #3 {{#subobject:fb3cbd|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|rowspan=2|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70027-0/abstract Ardeshna et al. 2014 (CRUK-2004-001621-16)]
+| rowspan="2" |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70027-0/abstract Ardeshna et al. 2014 (CRUK-2004-001621-16)]
-|rowspan=2 style="background-color:#1a9851"|Phase III (E-esc)
+| rowspan="2" style="background-color:#1a9851" |Phase III (E-esc)
 |1. [[#Observation_2|Observation]]
-|style="background-color:#1a9850"|Superior TTNT
+| style="background-color:#1a9850" |Superior TTNT
 |-
 |2. [[#Rituximab_monotherapy_2|Rituximab induction, no maintenance]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of TTNT
+| style="background-color:#ffffbf" |Did not meet primary endpoint of TTNT
 |-
 |}
 ====Preceding treatment====
 *[[#Rituximab_monotherapy_2|Rituximab induction]]
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows:
 **Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
@@ Line 2,062: / Line 2,245: @@
 ===Variant #4 {{#subobject:9aafa|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 20%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
 |[http://www.bloodjournal.org/content/124/21/3052 Rummel et al. 2014 (MAINTAIN)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Rituximab_monotherapy.2C_very_extended_course|Rituximab x 4y]]
 |TBD
@@ Line 2,075: / Line 2,258: @@
 |-
 |[http://link.springer.com/article/10.1007/s00277-014-2103-3/fulltext.html Witzens-Harig et al. 2014 (MAXIMA)]
-|style="background-color:#91cf61"|Non-randomized
+| style="background-color:#91cf61" |Non-randomized
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |
 |-
@@ Line 2,088: / Line 2,271: @@
 |}
 ====Preceding treatment====
 *MAINTAIN: [[#BR|BR x 6 and 2 doses of rituximab]]
 *MAXIMA: [[#Rituximab_monotherapy_2|Rituximab monotherapy]] or rituximab and chemotherapy (Most patients, 62%, received an anthracycline-based regimen)
@@ Line 2,093: / Line 2,277: @@
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 2,098: / Line 2,283: @@
 ===References===
-# '''Meta-analysis:''' Vidal L, Gafter-Gvili A, Leibovici L, Dreyling M, Ghielmini M, Hsu Schmitz SF, Cohen A, Shpilberg O. Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials. J Natl Cancer Inst. 2009 Feb 18;101(4):248-55. Epub 2009 Feb 10. [https://www.ncbi.nlm.nih.gov/pubmed/19211444 PubMed]
+#'''Meta-analysis:''' Vidal L, Gafter-Gvili A, Leibovici L, Dreyling M, Ghielmini M, Hsu Schmitz SF, Cohen A, Shpilberg O. Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials. J Natl Cancer Inst. 2009 Feb 18;101(4):248-55. Epub 2009 Feb 10. [https://www.ncbi.nlm.nih.gov/pubmed/19211444 PubMed]
 <!-- Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL, and the Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL. -->
-# '''ECOG E1496:''' Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. Epub 2009 Mar 2. [http://jco.ascopubs.org/content/27/10/1607.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668968/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19255334 PubMed]
+#'''ECOG E1496:''' Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. Epub 2009 Mar 2. [http://jco.ascopubs.org/content/27/10/1607.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668968/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19255334 PubMed]
-## '''Update:''' Barta SK, Li H, Hochster HS, Hong F, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Colocci N, Bengtson EM, Horning SJ, Kahl BS. Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496). Cancer. 2016 Oct;122(19):2996-3004. Epub 2016 Jun 28. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.30137/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030179/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27351685 PubMed]
+##'''Update:''' Barta SK, Li H, Hochster HS, Hong F, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Colocci N, Bengtson EM, Horning SJ, Kahl BS. Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496). Cancer. 2016 Oct;122(19):2996-3004. Epub 2016 Jun 28. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.30137/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030179/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27351685 PubMed]
-# '''PRIMA:''' Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2962175-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21176949 PubMed]
+#'''PRIMA:''' Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2962175-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21176949 PubMed]
-## '''QoL Analysis:''' Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. [http://www.maneyonline.com/doi/full/10.1179/1607845414Y.0000000179 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25029908 PubMed]
+##'''QoL Analysis:''' Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. [http://www.maneyonline.com/doi/full/10.1179/1607845414Y.0000000179 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25029908 PubMed]
-## '''Update:''' Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. [https://ascopubs.org/doi/full/10.1200/JCO.19.01073 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823890/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/31339826 PubMed]
+##'''Update:''' Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. [https://ascopubs.org/doi/full/10.1200/JCO.19.01073 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823890/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/31339826 PubMed]
-# '''CRUK-2004-001621-16:''' Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P, Warden J, Stevens L, Pocock CF, Miall F, Cunningham D, Davies J, Jack A, Stephens R, Walewski J, Ferhanoglu B, Bradstock K, Linch DC. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol. 2014 Apr;15(4):424-35. Epub 2014 Mar 4. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70027-0/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24602760 PubMed]
+#'''CRUK-2004-001621-16:''' Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P, Warden J, Stevens L, Pocock CF, Miall F, Cunningham D, Davies J, Jack A, Stephens R, Walewski J, Ferhanoglu B, Bradstock K, Linch DC. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol. 2014 Apr;15(4):424-35. Epub 2014 Mar 4. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70027-0/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24602760 PubMed]
-# '''MAXIMA:''' Witzens-Harig M, Foá R, Di Rocco A, van Hazel G, Chamone DF, Rowe JM, Arcaini L, Poddubnaya I, Ho AD, Ivanova V, Vranovsky A, Thurley D, Oertel S. Maintenance with rituximab is safe and not associated with severe or uncommon infections in patients with follicular lymphoma: results from the phase IIIb MAXIMA study. Ann Hematol. 2014 Oct;93(10):1717-24. Epub 2014 May 14. Erratum in: Ann Hematol. 2014 Oct;93(10):1807. [http://link.springer.com/article/10.1007/s00277-014-2103-3/fulltext.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24824768 PubMed]
+#'''MAXIMA:''' Witzens-Harig M, Foá R, Di Rocco A, van Hazel G, Chamone DF, Rowe JM, Arcaini L, Poddubnaya I, Ho AD, Ivanova V, Vranovsky A, Thurley D, Oertel S. Maintenance with rituximab is safe and not associated with severe or uncommon infections in patients with follicular lymphoma: results from the phase IIIb MAXIMA study. Ann Hematol. 2014 Oct;93(10):1717-24. Epub 2014 May 14. Erratum in: Ann Hematol. 2014 Oct;93(10):1807. [http://link.springer.com/article/10.1007/s00277-014-2103-3/fulltext.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24824768 PubMed]
-# '''Abstract:''' Mathias J. Rummel, MD, Andreas Viardot, Richard Greil, MD, Bernd Hertenstein, MD, Christian Lerchenmüller, MD, Arnold Ganser, Manfred Reeb, MD, Ulrich Kaiser, MD, Christina Balser, MD, Georg Maschmeyer, MD, Heinz Dürk, MD, Georg Schliesser, MD, Tobias Gaska, MD, Jan Dürig, MD, Axel C. Matzdorff, MD, Rudolf Weide, MD, Axel Hinke, PhD, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Jürgen Barth and Wolfram Brugger, MD. Bendamustine Plus Rituximab Followed By Rituximab Maintenance for Patients with Untreated Advanced Follicular Lymphomas. Results from the StiL NHL 7-2008 Trial (MAINTAIN trial) (ClinicalTrials.gov Identifier: NCT00877214). Blood 2014 124:3052. [http://www.bloodjournal.org/content/124/21/3052 link to abstract]
+#'''Abstract:''' Mathias J. Rummel, MD, Andreas Viardot, Richard Greil, MD, Bernd Hertenstein, MD, Christian Lerchenmüller, MD, Arnold Ganser, Manfred Reeb, MD, Ulrich Kaiser, MD, Christina Balser, MD, Georg Maschmeyer, MD, Heinz Dürk, MD, Georg Schliesser, MD, Tobias Gaska, MD, Jan Dürig, MD, Axel C. Matzdorff, MD, Rudolf Weide, MD, Axel Hinke, PhD, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Jürgen Barth and Wolfram Brugger, MD. Bendamustine Plus Rituximab Followed By Rituximab Maintenance for Patients with Untreated Advanced Follicular Lymphomas. Results from the StiL NHL 7-2008 Trial (MAINTAIN trial) (ClinicalTrials.gov Identifier: NCT00877214). Blood 2014 124:3052. [http://www.bloodjournal.org/content/124/21/3052 link to abstract]
-# '''SABRINA:''' Davies A, Merli F, Mihaljević B, Mercadal S, Siritanaratkul N, Solal-Céligny P, Boehnke A, Berge C, Genevray M, Zharkov A, Dixon M, Brewster M, Barrett M, MacDonald D. Efficacy and safety of subcutaneous rituximab versus intravenous rituximab for first-line treatment of follicular lymphoma (SABRINA): a randomised, open-label, phase 3 trial. Lancet Haematol. 2017 Jun;4(6):e272-e282. Epub 2017 May 2. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(17)30078-9/fulltext link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28476440 PubMed]
+#'''SABRINA:''' Davies A, Merli F, Mihaljević B, Mercadal S, Siritanaratkul N, Solal-Céligny P, Boehnke A, Berge C, Genevray M, Zharkov A, Dixon M, Brewster M, Barrett M, MacDonald D. Efficacy and safety of subcutaneous rituximab versus intravenous rituximab for first-line treatment of follicular lymphoma (SABRINA): a randomised, open-label, phase 3 trial. Lancet Haematol. 2017 Jun;4(6):e272-e282. Epub 2017 May 2. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(17)30078-9/fulltext link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28476440 PubMed]
-# '''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://www.nejm.org/doi/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains verified protocol in appendix''' [https://www.ncbi.nlm.nih.gov/pubmed/28976863 PubMed]
+#'''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://www.nejm.org/doi/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains verified protocol in appendix''' [https://www.ncbi.nlm.nih.gov/pubmed/28976863 PubMed]
-## '''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8960 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29856692 PubMed]
+##'''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8960 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29856692 PubMed]
 ==Rituximab monotherapy, very extended course {{#subobject:bae86f|Regimen=1}}==
@@ Line 2,120: / Line 2,306: @@
 ===Variant #1, 4 years {{#subobject:7102c5|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.bloodjournal.org/content/124/21/3052 Rummel et al. 2014 (MAINTAIN)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#Rituximab_monotherapy.2C_extended_course|Rituximab x 2 y]]
 |TBD
@@ Line 2,132: / Line 2,318: @@
 |}
 ====Preceding treatment====
 *[[#BR|BR x 6 and 2 doses of rituximab]]
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 2,140: / Line 2,329: @@
 ===Variant #2, 5 years {{#subobject:9621eb|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872010/ Taverna et al. 2015 (SAKK 35/03)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab]] x 9 mo
-|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 |-
 |}
 ====Preceding treatment====
 *[[#Rituximab_monotherapy_2|Rituximab]]
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows:
 **Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
@@ Line 2,162: / Line 2,354: @@
 ===Variant #3, indefinite {{#subobject:21ebbc|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171355/ Kahl et al. 2014 (RESORT)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#Rituximab_monotherapy_3|Rituximab]]; salvage
-|style="background-color:#ffffbf"|Did not meet primary endpoint of TTF
+| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
 |-
 |}
 ====Preceding treatment====
 *[[#Rituximab_monotherapy_2|Rituximab]]
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 2,181: / Line 2,376: @@
 ===References===
-# '''Abstract:''' Mathias J. Rummel, MD, Andreas Viardot, Richard Greil, MD, Bernd Hertenstein, MD, Christian Lerchenmüller, MD, Arnold Ganser, Manfred Reeb, MD, Ulrich Kaiser, MD, Christina Balser, MD, Georg Maschmeyer, MD, Heinz Dürk, MD, Georg Schliesser, MD, Tobias Gaska, MD, Jan Dürig, MD, Axel C. Matzdorff, MD, Rudolf Weide, MD, Axel Hinke, PhD, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Jürgen Barth and Wolfram Brugger, MD. Bendamustine Plus Rituximab Followed By Rituximab Maintenance for Patients with Untreated Advanced Follicular Lymphomas. Results from the StiL NHL 7-2008 Trial (MAINTAIN trial) (ClinicalTrials.gov Identifier: NCT00877214). Blood 2014 124:3052. [http://www.bloodjournal.org/content/124/21/3052 link to abstract]
-# '''ECOG E4402:''' Kahl BS, Hong F, Williams ME, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ. Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: Eastern Cooperative Oncology Group protocol E4402. J Clin Oncol. 2014 Oct 1;32(28):3096-102. Epub 2014 Aug 25. [http://jco.ascopubs.org/content/32/28/3096.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171355/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25154829 PubMed]
+#'''Abstract:''' Mathias J. Rummel, MD, Andreas Viardot, Richard Greil, MD, Bernd Hertenstein, MD, Christian Lerchenmüller, MD, Arnold Ganser, Manfred Reeb, MD, Ulrich Kaiser, MD, Christina Balser, MD, Georg Maschmeyer, MD, Heinz Dürk, MD, Georg Schliesser, MD, Tobias Gaska, MD, Jan Dürig, MD, Axel C. Matzdorff, MD, Rudolf Weide, MD, Axel Hinke, PhD, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Jürgen Barth and Wolfram Brugger, MD. Bendamustine Plus Rituximab Followed By Rituximab Maintenance for Patients with Untreated Advanced Follicular Lymphomas. Results from the StiL NHL 7-2008 Trial (MAINTAIN trial) (ClinicalTrials.gov Identifier: NCT00877214). Blood 2014 124:3052. [http://www.bloodjournal.org/content/124/21/3052 link to abstract]
+#'''ECOG E4402:''' Kahl BS, Hong F, Williams ME, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ. Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: Eastern Cooperative Oncology Group protocol E4402. J Clin Oncol. 2014 Oct 1;32(28):3096-102. Epub 2014 Aug 25. [http://jco.ascopubs.org/content/32/28/3096.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171355/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25154829 PubMed]
 <!-- # '''Abstract:''' Taverna CJ, Bassi S, Hitz F, et al. Rituximab maintenance treatment for a maximum of 5 years in follicular lymphoma: Safety analysis of the randomized phase III trial SAKK 35/03 (Abstract 1802) Blood. 2010;116 [https://ash.confex.com/ash/2010/webprogram/Paper30282.html link to abstract]
 ## '''Abstract:''' '''Update:''' Christian J. Taverna, MD, Giovanni Martinelli, Felicitas Hitz, Walter Mingrone, Thomas Pabst, MD, Lidija Cevreska, Auro del Giglio, MD, Anna Vanazzi, Daniele Laszlo, Johann Raats, Daniel Rauch, Daniel A. Vorobiof, Andreas Lohri, MD, Emanuele Zucca, MD, Christine Biaggi Rudolf, Stephanie Rondeau, Corinne Rusterholz and Michele Ghielmini, MD. Rituximab Maintenance Treatment For a Maximum Of 5 Years In Follicular Lymphoma: Results Of The Randomized Phase III Trial SAKK 35/03. 2013 ASH Annual Meeting [https://ash.confex.com/ash/2013/webprogram/Paper61955.html link to abstract] -->
-# '''SAKK 35/03:''' Taverna C, Martinelli G, Hitz F, Mingrone W, Pabst T, Cevreska L, Del Giglio A, Vanazzi A, Laszlo D, Raats J, Rauch D, Vorobiof DA, Lohri A, Biaggi Rudolf C, Rondeau S, Rusterholz C, Heijnen IA, Zucca E, Ghielmini M. Rituximab maintenance for a maximum of 5 years after single-agent rituximab induction in follicular lymphoma: results of the randomized controlled phase III trial SAKK 35/03. J Clin Oncol. 2016 Feb 10;34(5):495-500. Epub 2015 Dec 28. [http://jco.ascopubs.org/content/34/5/495.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872010/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26712227 PubMed]
+#'''SAKK 35/03:''' Taverna C, Martinelli G, Hitz F, Mingrone W, Pabst T, Cevreska L, Del Giglio A, Vanazzi A, Laszlo D, Raats J, Rauch D, Vorobiof DA, Lohri A, Biaggi Rudolf C, Rondeau S, Rusterholz C, Heijnen IA, Zucca E, Ghielmini M. Rituximab maintenance for a maximum of 5 years after single-agent rituximab induction in follicular lymphoma: results of the randomized controlled phase III trial SAKK 35/03. J Clin Oncol. 2016 Feb 10;34(5):495-500. Epub 2015 Dec 28. [http://jco.ascopubs.org/content/34/5/495.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872010/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26712227 PubMed]
 ==Rituximab and hyaluronidase monotherapy {{#subobject:e26769|Regimen=1}}==
@@ Line 2,194: / Line 2,390: @@
 ===Regimen {{#subobject:4cba82|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(17)30078-9/fulltext Davies et al. 2017 (SABRINA)]
-|style="background-color:#1a9851"|Phase III (E-RT-switch-ic)
+| style="background-color:#1a9851" |Phase III (E-RT-switch-ic)
 |[[#Rituximab_monotherapy.2C_extended_course|IV Rituximab]]
 | style="background-color:#ffffbf" |Similar efficacy
@@ Line 2,207: / Line 2,403: @@
 ''Starts 8 weeks after the last induction treatment.''
 ====Preceding treatment====
 *[[#R-CHOP|R-CHOP]] or [[#R-CVP|R-CVP]]
 ====Chemotherapy====
 *[[Rituximab and hyaluronidase human (Rituxan Hycela)]] 1400 mg SC once on day 1
@@ Line 2,214: / Line 2,413: @@
 ===References===
-# '''SABRINA:''' Davies A, Merli F, Mihaljević B, Mercadal S, Siritanaratkul N, Solal-Céligny P, Boehnke A, Berge C, Genevray M, Zharkov A, Dixon M, Brewster M, Barrett M, MacDonald D. Efficacy and safety of subcutaneous rituximab versus intravenous rituximab for first-line treatment of follicular lymphoma (SABRINA): a randomised, open-label, phase 3 trial. Lancet Haematol. 2017 Jun;4(6):e272-e282. Epub 2017 May 2. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(17)30078-9/fulltext link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28476440 PubMed]
+#'''SABRINA:''' Davies A, Merli F, Mihaljević B, Mercadal S, Siritanaratkul N, Solal-Céligny P, Boehnke A, Berge C, Genevray M, Zharkov A, Dixon M, Brewster M, Barrett M, MacDonald D. Efficacy and safety of subcutaneous rituximab versus intravenous rituximab for first-line treatment of follicular lymphoma (SABRINA): a randomised, open-label, phase 3 trial. Lancet Haematol. 2017 Jun;4(6):e272-e282. Epub 2017 May 2. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(17)30078-9/fulltext link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28476440 PubMed]
 ==VR {{#subobject:5ca4d9|Regimen=1}}==
@@ Line 2,224: / Line 2,424: @@
 ===Regimen {{#subobject:8a6b14|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626332/ Cohen et al. 2015]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Preceding treatment====
 *[[#VR-CHOP|VR-CHOP]] x 6 to 8
 ====Chemotherapy====
 *[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
@@ Line 2,240: / Line 2,443: @@
 ===References===
-# Cohen JB, Switchenko JM, Koff JL, Sinha R, Kaufman JL, Khoury HJ, Bumpers N, Colbert A, Hutchison-Rzepka A, Nastoupil LJ, Heffner LT, Langston AA, Lechowicz MJ, Lonial S, Flowers CR. A phase II study of bortezomib added to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients with previously untreated indolent non-Hodgkin's lymphoma. Br J Haematol. 2015 Nov;171(4):539-46. Epub 2015 Aug 7. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13637/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626332/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26248505 PubMed]
+#Cohen JB, Switchenko JM, Koff JL, Sinha R, Kaufman JL, Khoury HJ, Bumpers N, Colbert A, Hutchison-Rzepka A, Nastoupil LJ, Heffner LT, Langston AA, Lechowicz MJ, Lonial S, Flowers CR. A phase II study of bortezomib added to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients with previously untreated indolent non-Hodgkin's lymphoma. Br J Haematol. 2015 Nov;171(4):539-46. Epub 2015 Aug 7. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13637/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626332/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26248505 PubMed]
 =Relapsed or refractory, randomized data=
@@ Line 2,252: / Line 2,456: @@
 ===Regimen {{#subobject:bcd5ef|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/26/2/204.long Friedberg et al. 2008]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916680/ Kahl et al. 2010]
-|style="background-color:#91cf61"|Phase II (RT)
+| style="background-color:#91cf61" |Phase II (RT)
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30097-3/fulltext Sehn et al. 2016 (GADOLIN)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Bendamustine_.26_Obinutuzumab_2|Bendamustine & Obinutuzumab]]
 | style="background-color:#fc8d59" |Seems to have inferior OS (*)
@@ Line 2,275: / Line 2,479: @@
 ''Note: efficacy in GADOLIN is based on the 2018 update.''
 ====Chemotherapy====
 *[[Bendamustine]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2
@@ Line 2,281: / Line 2,486: @@
 ===References===
 <!-- Presented in part at the 48th Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, Florida -->
-# Friedberg JW, Cohen P, Chen L, Robinson KS, Forero-Torres A, La Casce AS, Fayad LE, Bessudo A, Camacho ES, Williams ME, van der Jagt RH, Oliver JW, Cheson BD. Bendamustine in patients with rituximab-refractory indolent and transformed non-Hodgkin's lymphoma: results from a phase II multicenter, single-agent study. J Clin Oncol. 2008 Jan 10;26(2):204-10. Erratum in: J Clin Oncol. 2008 Apr 10;26(11) 1911. [http://jco.ascopubs.org/content/26/2/204.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18182663 PubMed]
+#Friedberg JW, Cohen P, Chen L, Robinson KS, Forero-Torres A, La Casce AS, Fayad LE, Bessudo A, Camacho ES, Williams ME, van der Jagt RH, Oliver JW, Cheson BD. Bendamustine in patients with rituximab-refractory indolent and transformed non-Hodgkin's lymphoma: results from a phase II multicenter, single-agent study. J Clin Oncol. 2008 Jan 10;26(2):204-10. Erratum in: J Clin Oncol. 2008 Apr 10;26(11) 1911. [http://jco.ascopubs.org/content/26/2/204.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18182663 PubMed]
 <!-- Preliminary research findings from this study were presented at the 2007 American Society of Hematology Annual Meeting and Exposition, Atlanta, Georgia, December 8-11, 2007. -->
-# Kahl BS, Bartlett NL, Leonard JP, Chen L, Ganjoo K, Williams ME, Czuczman MS, Robinson KS, Joyce R, van der Jagt RH, Cheson BD. Bendamustine is effective therapy in patients with rituximab-refractory, indolent B-cell non-Hodgkin lymphoma: results from a multicenter study. Cancer. 2010 Jan 1;116(1):106-14. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.24714/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916680/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19890959 PubMed]
+#Kahl BS, Bartlett NL, Leonard JP, Chen L, Ganjoo K, Williams ME, Czuczman MS, Robinson KS, Joyce R, van der Jagt RH, Cheson BD. Bendamustine is effective therapy in patients with rituximab-refractory, indolent B-cell non-Hodgkin lymphoma: results from a multicenter study. Cancer. 2010 Jan 1;116(1):106-14. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.24714/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916680/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19890959 PubMed]
 <!-- # '''Abstract:''' Laurie Helen Sehn, Neil Sun Chua, Jiri Mayer, Gregory Scott Dueck, Marek Trněný, Kamal Bouabdallah, Nathan Hale Fowler, Vincent Delwail, Oliver W. Press, Gilles A. Salles, John G. Gribben, Anne Lennard, Pieternella J. Lugtenburg, Natalie Franklin, Elisabeth Wassner Fritsch, Guenter Fingerle-Rowson, Bruce D. Cheson. GADOLIN: Primary results from a phase III study of obinutuzumab plus bendamustine compared with bendamustine alone in patients with rituximab-refractory indolent non-Hodgkin lymphoma. J Clin Oncol 33, 2015 (suppl; abstr LBA8502) [http://meetinglibrary.asco.org/content/147837-156 link to abstract] -->
-# '''GADOLIN:''' Sehn LH, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben J, Lennard A, Lugtenburg PJ, Dimier N, Wassner-Fritsch E, Fingerle-Rowson G, Cheson BD. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1081-93. Epub 2016 Jun 23. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30097-3/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27345636 PubMed]
+#'''GADOLIN:''' Sehn LH, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben J, Lennard A, Lugtenburg PJ, Dimier N, Wassner-Fritsch E, Fingerle-Rowson G, Cheson BD. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1081-93. Epub 2016 Jun 23. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30097-3/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27345636 PubMed]
-## '''Update:''' Cheson BD, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben JG, Lennard A, Lugtenburg PJ, Fingerle-Rowson G, Mattiello F, Knapp A, Sehn LH. Overall survival benefit in patients with rituximab-refractory indolent non-Hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study. J Clin Oncol. 2018 Aug 1;36(22):2259-2266. Epub 2018 Mar 27. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.3656 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29584548 PubMed]
+##'''Update:''' Cheson BD, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben JG, Lennard A, Lugtenburg PJ, Fingerle-Rowson G, Mattiello F, Knapp A, Sehn LH. Overall survival benefit in patients with rituximab-refractory indolent non-Hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study. J Clin Oncol. 2018 Aug 1;36(22):2259-2266. Epub 2018 Mar 27. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.3656 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29584548 PubMed]
 ==Bendamustine & Obinutuzumab {{#subobject:8346cc|Regimen=1}}==
@@ Line 2,296: / Line 2,502: @@
 ===Regimen {{#subobject:5f3683|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30097-3/fulltext Sehn et al. 2016 (GADOLIN)]
-|style="background-color:#1a9851"|Phase III (E-RT-esc)
+| style="background-color:#1a9851" |Phase III (E-RT-esc)
 |[[#Bendamustine_monotherapy|Bendamustine]]
 | style="background-color:#91cf60" |Seems to have superior OS
@@ Line 2,309: / Line 2,515: @@
 ''Note: efficacy is based on the 2018 update.''
 ====Chemotherapy====
 *[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 *[[Obinutuzumab (Gazyva)]] as follows:
@@ Line 2,316: / Line 2,523: @@
 '''28-day cycle for 6 cycles'''
 ====Subsequent treatment====
 *[[#Obinutuzumab_monotherapy_4|Obinutuzumab maintenance]]
 ===References===
 <!-- # '''Abstract:''' Laurie Helen Sehn, Neil Sun Chua, Jiri Mayer, Gregory Scott Dueck, Marek Trněný, Kamal Bouabdallah, Nathan Hale Fowler, Vincent Delwail, Oliver W. Press, Gilles A. Salles, John G. Gribben, Anne Lennard, Pieternella J. Lugtenburg, Natalie Franklin, Elisabeth Wassner Fritsch, Guenter Fingerle-Rowson, Bruce D. Cheson. GADOLIN: Primary results from a phase III study of obinutuzumab plus bendamustine compared with bendamustine alone in patients with rituximab-refractory indolent non-Hodgkin lymphoma. J Clin Oncol 33, 2015 (suppl; abstr LBA8502) [http://meetinglibrary.asco.org/content/147837-156 link to abstract] -->
-# '''GADOLIN:''' Sehn LH, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben J, Lennard A, Lugtenburg PJ, Dimier N, Wassner-Fritsch E, Fingerle-Rowson G, Cheson BD. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1081-93. Epub 2016 Jun 23. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30097-3/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27345636 PubMed]
-## '''Update:''' Cheson BD, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben JG, Lennard A, Lugtenburg PJ, Fingerle-Rowson G, Mattiello F, Knapp A, Sehn LH. Overall survival benefit in patients with rituximab-refractory indolent non-Hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study. J Clin Oncol. 2018 Aug 1;36(22):2259-2266. Epub 2018 Mar 27. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.3656 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29584548 PubMed]
+#'''GADOLIN:''' Sehn LH, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben J, Lennard A, Lugtenburg PJ, Dimier N, Wassner-Fritsch E, Fingerle-Rowson G, Cheson BD. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1081-93. Epub 2016 Jun 23. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30097-3/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27345636 PubMed]
+##'''Update:''' Cheson BD, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben JG, Lennard A, Lugtenburg PJ, Fingerle-Rowson G, Mattiello F, Knapp A, Sehn LH. Overall survival benefit in patients with rituximab-refractory indolent non-Hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study. J Clin Oncol. 2018 Aug 1;36(22):2259-2266. Epub 2018 Mar 27. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.3656 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29584548 PubMed]
 ==Bevacizumab & Rituximab {{#subobject:82f5ed|Regimen=1}}==
@@ Line 2,331: / Line 2,540: @@
 ===Regimen {{#subobject:db036c|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00052-4/fulltext Hainsworth et al. 2014]
-|style="background-color:#1a9851"|Randomized (E-esc)
+| style="background-color:#1a9851" |Randomized (E-esc)
 |[[#Rituximab_monotherapy_3|Rituximab]]
-|style="background-color:#91cf60"|Seems to have superior PFS
+| style="background-color:#91cf60" |Seems to have superior PFS
 |-
 |}
 ====Chemotherapy====
 *[[Bevacizumab (Avastin)]] as follows:
 **Cycle 1: 10 mg/kg IV once per day on days 3 & 15
@@ Line 2,353: / Line 2,563: @@
 ===References===
-# Hainsworth JD, Greco FA, Raefsky EL, Thompson DS, Lunin S, Reeves J Jr, White L, Quinn R, DeBusk LM, Flinn IW. Rituximab with or without bevacizumab for the treatment of patients with relapsed follicular lymphoma. Clin Lymphoma Myeloma Leuk. 2014 Aug;14(4):277-83. Epub 2014 Feb 28. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00052-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24679633 PubMed]
+#Hainsworth JD, Greco FA, Raefsky EL, Thompson DS, Lunin S, Reeves J Jr, White L, Quinn R, DeBusk LM, Flinn IW. Rituximab with or without bevacizumab for the treatment of patients with relapsed follicular lymphoma. Clin Lymphoma Myeloma Leuk. 2014 Aug;14(4):277-83. Epub 2014 Feb 28. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00052-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24679633 PubMed]
 ==BR {{#subobject:981d90|Regimen=1}}==
@@ Line 2,363: / Line 2,574: @@
 ===Variant #1, 4 cycles {{#subobject:f5ca0d|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://link.springer.com/article/10.1007/s12185-015-1767-3/fulltext.html Matsumoto et al. 2015 (BRB)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Note: rituximab could be given on day 0, 1, 2, or 3 "according to the clinical convenience of each institution."''
 ====Chemotherapy====
-*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
+*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 2,379: / Line 2,591: @@
 ===Variant #2, 4 cycles with rituximab lead-in {{#subobject:7d5704|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://ascopubs.org/doi/full/10.1200/jco.2005.08.100 Rummel et al. 2005]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |[http://jco.ascopubs.org/content/26/27/4473.long Robinson et al. 2008]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Note: Robinson et al. 2008 said that patients "could receive up to six cycles if disease regression was evident between the second and fourth cycles".''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows:
 **One week prior to start of cycle 1: 375 mg/m<sup>2</sup> IV once
@@ Line 2,401: / Line 2,614: @@
 ===Variant #3, 6 cycles {{#subobject:nc810d|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00447-7/fulltext Rummel et al. 2015 (StiL NHL 2-2003)]
-|style="background-color:#1a9851"|Phase III (E-switch-ic)
+| style="background-color:#1a9851" |Phase III (E-switch-ic)
 |[[Follicular_lymphoma_-_historical#FR|FR]]
-|style="background-color:#1a9850"|Superior PFS
+| style="background-color:#1a9850" |Superior PFS
 |-
 |}
 ====Chemotherapy====
-*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
-*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
+*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 '''28-day cycle for up to 6 cycles'''
 ===References===
-# Rummel MJ, Al-Batran SE, Kim SZ, Welslau M, Hecker R, Kofahl-Krause D, Josten KM, Dürk H, Rost A, Neise M, von Grünhagen U, Chow KU, Hansmann ML, Hoelzer D, Mitrou PS. Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin's lymphoma. J Clin Oncol. 2005 May 20;23(15):3383-9. [https://ascopubs.org/doi/full/10.1200/jco.2005.08.100 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15908650 PubMed]
-# Robinson KS, Williams ME, van der Jagt RH, Cohen P, Herst JA, Tulpule A, Schwartzberg LS, Lemieux B, Cheson BD. Phase II multicenter study of bendamustine plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin's lymphoma. J Clin Oncol. 2008 Sep 20;26(27):4473-9. Epub 2008 Jul 14. [http://jco.ascopubs.org/content/26/27/4473.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18626004 PubMed]
+#Rummel MJ, Al-Batran SE, Kim SZ, Welslau M, Hecker R, Kofahl-Krause D, Josten KM, Dürk H, Rost A, Neise M, von Grünhagen U, Chow KU, Hansmann ML, Hoelzer D, Mitrou PS. Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin's lymphoma. J Clin Oncol. 2005 May 20;23(15):3383-9. [https://ascopubs.org/doi/full/10.1200/jco.2005.08.100 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15908650 PubMed]
-# '''BRB:''' Matsumoto K, Takayama N, Aisa Y, Ueno H, Hagihara M, Watanabe K, Nakaya A, Chen K, Shimizu T, Tsukada Y, Yamada Y, Nakazato T, Ishida A, Miyakawa Y, Yokoyama K, Nakajima H, Masuda Y, Yano T, Okamoto S; Keio BRB Study Group. A phase II study of bendamustine plus rituximab in Japanese patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma previously treated with rituximab: BRB study. Int J Hematol. 2015 Jun;101(6):554-62. Epub 2015 Mar 19. [http://link.springer.com/article/10.1007/s12185-015-1767-3/fulltext.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25783753 PubMed]
+#Robinson KS, Williams ME, van der Jagt RH, Cohen P, Herst JA, Tulpule A, Schwartzberg LS, Lemieux B, Cheson BD. Phase II multicenter study of bendamustine plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin's lymphoma. J Clin Oncol. 2008 Sep 20;26(27):4473-9. Epub 2008 Jul 14. [http://jco.ascopubs.org/content/26/27/4473.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18626004 PubMed]
+#'''BRB:''' Matsumoto K, Takayama N, Aisa Y, Ueno H, Hagihara M, Watanabe K, Nakaya A, Chen K, Shimizu T, Tsukada Y, Yamada Y, Nakazato T, Ishida A, Miyakawa Y, Yokoyama K, Nakajima H, Masuda Y, Yano T, Okamoto S; Keio BRB Study Group. A phase II study of bendamustine plus rituximab in Japanese patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma previously treated with rituximab: BRB study. Int J Hematol. 2015 Jun;101(6):554-62. Epub 2015 Mar 19. [http://link.springer.com/article/10.1007/s12185-015-1767-3/fulltext.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25783753 PubMed]
 <!-- # '''Abstract:''' Mathias J. Rummel, MD, PhD, Ulrich Kaiser, MD, Christina Balser, Martina Beate Stauch, Wolfram Brugger, MD, PhD, Manfred Welslau, Norbert Niederle, Christoph Losem, Harald Ballo, Eckhart Weidmann, Ulrich von Gruenhagen, Lothar Mueller, Michael Sandherr, MD, Julia Vereschagina, Axel Hinke and Juergen Barth. Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab In Patients with Relapsed Follicular, Indolent and Mantle Cell Lymphomas – Final Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany). ASH Annual Meeting 2010, Abstract 856 [https://ash.confex.com/ash/2010/webprogram/Paper26917.html link to abstract]
 ## '''Update:''' '''Abstract:''' Mathias J. Rummel, MD, Christina Balser, MD, Ulrich Kaiser, MD, Hans Peter Böck, Martina Beate Stauch, MD, Andrea Heider, PhD, Manfred Welslau, Christoph Losem, Eckhart Weidmann, Wolfgang Blau, MD, Alexander Burchardt, MD, Jürgen Barth, Frank Kauff, PhD, Axel Hinke, PhD and Wolfram Brugger, MD. Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab in Patients with Relapsed Follicular, Indolent, or Mantle Cell Lymphomas – 8-Year Follow-up Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany). ASH Annual Meeting 2014, Abstract 145 [https://ash.confex.com/ash/2014/webprogram/Paper69154.html link to abstract] -->
-# '''StiL NHL 2-2003:''' Rummel M, Kaiser U, Balser C, Stauch M, Brugger W, Welslau M, Niederle N, Losem C, Boeck HP, Weidmann E, von Gruenhagen U, Mueller L, Sandherr M, Hahn L, Vereshchagina J, Kauff F, Blau W, Hinke A, Barth J; Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial. Lancet Oncol. 2016 Jan;17(1):57-66. Epub 2015 Dec 5. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00447-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26655425 PubMed]
+#'''StiL NHL 2-2003:''' Rummel M, Kaiser U, Balser C, Stauch M, Brugger W, Welslau M, Niederle N, Losem C, Boeck HP, Weidmann E, von Gruenhagen U, Mueller L, Sandherr M, Hahn L, Vereshchagina J, Kauff F, Blau W, Hinke A, Barth J; Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial. Lancet Oncol. 2016 Jan;17(1):57-66. Epub 2015 Dec 5. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00447-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26655425 PubMed]
 ==Ibritumomab tiuxetan monotherapy {{#subobject:b0c8fb|Regimen=1}}==
@@ Line 2,433: / Line 2,648: @@
 ===Variant #1, 0.3 mCi/kg {{#subobject:1fc7u3|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 50%"|Study
+! style="width: 50%" |Study
-!style="width: 50%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.bloodjournal.org/content/99/12/4336.long Wiseman et al. 2002]
@@ Line 2,442: / Line 2,657: @@
 ''Note: this dosing was intended for patients with mild thrombocytopenia.''
 ====Radioimmunotherapy====
 *[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 *[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan 1.6 mg & Indium-111 5 mCi]] IV over 10 minutes once on day 1
-*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] 0.3 mCi/kg (11 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV over 10 minutes once on day 8, '''given immediately following rituximab'''
+*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 0.3 mCi/kg (11 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV over 10 minutes once on day 8, '''given immediately following rituximab'''
 '''8-day course'''
@@ Line 2,450: / Line 2,666: @@
 ===Variant #2, 0.4 mCi/kg {{#subobject:1fc8c3|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/17/12/3793.long Witzig et al. 1999]
-|style="background-color:#91cf61"|Phase I/II
+| style="background-color:#91cf61" |Phase I/II
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
 |-
 |[http://jco.ascopubs.org/content/20/10/2453.long Witzig et al. 2002a]
-|style="background-color:#1a9851"|Phase III (E-RT-switch-ic)
+| style="background-color:#1a9851" |Phase III (E-RT-switch-ic)
 |[[#Rituximab_monotherapy_3|Rituximab]]
-|style="background-color:#1a9850"|Superior ORR
+| style="background-color:#1a9850" |Superior ORR
 |-
 |[http://jco.ascopubs.org/content/20/15/3262.long Witzig et al. 2002b]
-|style="background-color:#91cf61"|Phase II (RT)
+| style="background-color:#91cf61" |Phase II (RT)
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
@@ Line 2,473: / Line 2,689: @@
 ''Witzig et al. 2002b was intended for patients with rituximab-refractory disease.''
 ====Radioimmunotherapy====
 *[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 *[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan 1.6 mg & Indium-111 5 mCi]] IV over 10 minutes once on day 1
-*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] 0.4 mCi/kg (15 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV over 10 minutes once on day 8, '''given immediately following rituximab'''
+*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 0.4 mCi/kg (15 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV over 10 minutes once on day 8, '''given immediately following rituximab'''
 '''8-day course'''
 ===References===
-# Witzig TE, White CA, Wiseman GA, Gordon LI, Emmanouilides C, Raubitschek A, Janakiraman N, Gutheil J, Schilder RJ, Spies S, Silverman DH, Parker E, Grillo-López AJ. Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec;17(12):3793-803. [http://jco.ascopubs.org/content/17/12/3793.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10577851 PubMed]
-# Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, Pohlman BL, Bartlett NL, Wiseman GA, Padre N, Grillo-López AJ, Multani P, White CA. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2002 May 15;20(10):2453-63. [http://jco.ascopubs.org/content/20/10/2453.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12011122 PubMed]
+#Witzig TE, White CA, Wiseman GA, Gordon LI, Emmanouilides C, Raubitschek A, Janakiraman N, Gutheil J, Schilder RJ, Spies S, Silverman DH, Parker E, Grillo-López AJ. Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec;17(12):3793-803. [http://jco.ascopubs.org/content/17/12/3793.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10577851 PubMed]
-# Wiseman GA, Gordon LI, Multani PS, Witzig TE, Spies S, Bartlett NL, Schilder RJ, Murray JL, Saleh M, Allen RS, Grillo-López AJ, White CA. Ibritumomab tiuxetan radioimmunotherapy for patients with relapsed or refractory non-Hodgkin lymphoma and mild thrombocytopenia: a phase II multicenter trial. Blood. 2002 Jun 15;99(12):4336-42. [http://www.bloodjournal.org/content/99/12/4336.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12036859 PubMed]
+#Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, Pohlman BL, Bartlett NL, Wiseman GA, Padre N, Grillo-López AJ, Multani P, White CA. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2002 May 15;20(10):2453-63. [http://jco.ascopubs.org/content/20/10/2453.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12011122 PubMed]
-# Witzig TE, Flinn IW, Gordon LI, Emmanouilides C, Czuczman MS, Saleh MN, Cripe L, Wiseman G, Olejnik T, Multani PS, White CA. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin's lymphoma. J Clin Oncol. 2002 Aug 1;20(15):3262-9. [http://jco.ascopubs.org/content/20/15/3262.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12149300 PubMed]
+#Wiseman GA, Gordon LI, Multani PS, Witzig TE, Spies S, Bartlett NL, Schilder RJ, Murray JL, Saleh M, Allen RS, Grillo-López AJ, White CA. Ibritumomab tiuxetan radioimmunotherapy for patients with relapsed or refractory non-Hodgkin lymphoma and mild thrombocytopenia: a phase II multicenter trial. Blood. 2002 Jun 15;99(12):4336-42. [http://www.bloodjournal.org/content/99/12/4336.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12036859 PubMed]
+#Witzig TE, Flinn IW, Gordon LI, Emmanouilides C, Czuczman MS, Saleh MN, Cripe L, Wiseman G, Olejnik T, Multani PS, White CA. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin's lymphoma. J Clin Oncol. 2002 Aug 1;20(15):3262-9. [http://jco.ascopubs.org/content/20/15/3262.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12149300 PubMed]
 ==Lenalidomide monotherapy {{#subobject:d9b3c|Regimen=1}}==
@@ Line 2,493: / Line 2,711: @@
 ===Variant #1, up to 12 cycles {{#subobject:c408a4|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/33/31/3635.full Leonard et al. 2015 (CALGB 50401)]
-|style="background-color:#1a9851"|Randomized Phase II (E-de-esc)
+| style="background-color:#1a9851" |Randomized Phase II (E-de-esc)
 |[[#Lenalidomide_.26_Rituximab_3|Lenalidomide & Rituximab]]
-|style="background-color:#d73027"|Inferior TTP
+| style="background-color:#d73027" |Inferior TTP
 |-
 |}
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] as follows:
 **Cycle 1: 15 mg PO once per day on days 1 to 21
@@ Line 2,511: / Line 2,730: @@
 ====Supportive medications====
 *[[Aspirin]] or [[:Category:Low molecular weight heparins|LMWH]] recommended for patients at high risk of thrombosis (see paper for details)
@@ Line 2,517: / Line 2,737: @@
 ===Variant #2, indefinite {{#subobject:ac829f|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://jco.ascopubs.org/content/27/32/5404.full Witzig et al. 2009 (NHL-001)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
@@ Line 2,531: / Line 2,752: @@
 ===References===
 <!-- Presented in part in poster format at the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 1-5, 2007, the 49th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 8-11, 2007, and the 13th Annual Meeting of the European Hematology Association, Copenhagen, Denmark, June 12-15, 2008. -->
-# Witzig TE, Wiernik PH, Moore T, Reeder C, Cole C, Justice G, Kaplan H, Voralia M, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Vose JM. Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin's Lymphoma. J Clin Oncol. 2009 Nov 10;27(32):5404-9. Epub 2009 Oct 5. [http://jco.ascopubs.org/content/27/32/5404.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19805688 PubMed]
+#Witzig TE, Wiernik PH, Moore T, Reeder C, Cole C, Justice G, Kaplan H, Voralia M, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Vose JM. Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin's Lymphoma. J Clin Oncol. 2009 Nov 10;27(32):5404-9. Epub 2009 Oct 5. [http://jco.ascopubs.org/content/27/32/5404.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19805688 PubMed]
 <!-- # '''Abstract:''' John Leonard, Sin-Ho Jung, Jeffrey L. Johnson, Nancy Bartlett, Kristie A. Blum, Bruce D. Cheson. CALGB 50401: A randomized trial of lenalidomide alone versus lenalidomide plus rituximab in patients with recurrent follicular lymphoma. J Clin Oncol 30, 2012 (suppl; abstr 8000) [http://meetinglibrary.asco.org/content/93509-114 link to abstract] -->
-# Leonard JP, Jung SH, Johnson J, Pitcher BN, Bartlett NL, Blum KA, Czuczman M, Giguere JK, Cheson BD. Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). J Clin Oncol. 2015 Nov 1;33(31):3635-40. Epub 2015 Aug 24. [http://jco.ascopubs.org/content/33/31/3635.full link to full article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622102/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26304886 PubMed]
+#Leonard JP, Jung SH, Johnson J, Pitcher BN, Bartlett NL, Blum KA, Czuczman M, Giguere JK, Cheson BD. Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). J Clin Oncol. 2015 Nov 1;33(31):3635-40. Epub 2015 Aug 24. [http://jco.ascopubs.org/content/33/31/3635.full link to full article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622102/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26304886 PubMed]
 ==Lenalidomide & Rituximab {{#subobject:00ba12|Regimen=1}}==
@@ Line 2,542: / Line 2,764: @@
 ===Variant #1, len 10 {{#subobject:c5580d|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://clincancerres.aacrjournals.org/content/21/8/1835.full Chong et al. 2015]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 10 mg PO once per day
 *[[Rituximab (Rituxan)]] as follows:
@@ Line 2,558: / Line 2,781: @@
 ===Variant #2, len dose escalation 15 -> 25 x 12 {{#subobject:20e899|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://jco.ascopubs.org/content/33/31/3635.full Leonard et al. 2015 (CALGB 50401)]
-|style="background-color:#1a9851"|Randomized Phase II (E-esc)
+| style="background-color:#1a9851" |Randomized Phase II (E-esc)
 |[[#Lenalidomide_monotherapy|Lenalidomide]]
-|style="background-color:#1a9850"|Superior TTP
+| style="background-color:#1a9850" |Superior TTP
 |-
 |}
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] as follows:
 **Cycle 1: 15 mg PO once per day on days 1 to 21
@@ Line 2,578: / Line 2,802: @@
 ====Supportive medications====
 *[[Aspirin]] or [[:Category:Low molecular weight heparins|LMWH]] recommended for patients at high risk of thrombosis (see paper for details)
@@ Line 2,584: / Line 2,809: @@
 ===Variant #3, len 20 x 2 {{#subobject:c6480d|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.12755/full Tuscano et al. 2014]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 *[[Rituximab (Rituxan)]] as follows:
 **Cycle 1: 375 mg/m<sup>2</sup> IV once on day 15
 **Cycle 2: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 ====Supportive medications====
 *[[Allopurinol (Zyloprim)]] as follows:
 **Cycle 1: 300 mg PO once per day
@@ Line 2,604: / Line 2,831: @@
 '''28-day cycle for 2 cycles'''
 ====Subsequent treatment====
 *Responders: [[#Lenalidomide_monotherapy_2|Lenalidomide maintenance]]
 *Patients with less than a CR after induction: more rituximab could be given at the discretion of the treating physician. Dosing details not provided in the reference
@@ Line 2,613: / Line 2,841: @@
 |}
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.19.00010 Leonard et al. 2019 (AUGMENT)]
-|style="background-color:#1a9851"|Phase III (E-RT-esc)
+| style="background-color:#1a9851" |Phase III (E-RT-esc)
 |[[#Lenalidomide_monotherapy|Lenalidomide]]
-|style="background-color:#1a9850"|Superior PFS
+| style="background-color:#1a9850" |Superior PFS
 |-
 |}
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 *[[Rituximab (Rituxan)]] as follows:
@@ Line 2,633: / Line 2,862: @@
 ===References===
-# Tuscano JM, Dutia M, Chee K, Brunson A, Reed-Pease C, Abedi M, Welborn J, O'Donnell RT. Lenalidomide plus rituximab can produce durable clinical responses in patients with relapsed or refractory, indolent non-Hodgkin lymphoma. Br J Haematol. 2014 May;165(3):375-81. Epub 2014 Mar 7. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12755/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24606326 PubMed]
-# Chong EA, Ahmadi T, Aqui NA, Svoboda J, Nasta SD, Mato AR, Walsh KM, Schuster SJ. Combination of lenalidomide and rituximab overcomes rituximab resistance in patients with indolent B-cell and mantle cell lymphomas. Clin Cancer Res. 2015 Apr 15;21(8):1835-42. Epub 2015 Jan 28. [http://clincancerres.aacrjournals.org/content/21/8/1835.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25632047 PubMed]
+#Tuscano JM, Dutia M, Chee K, Brunson A, Reed-Pease C, Abedi M, Welborn J, O'Donnell RT. Lenalidomide plus rituximab can produce durable clinical responses in patients with relapsed or refractory, indolent non-Hodgkin lymphoma. Br J Haematol. 2014 May;165(3):375-81. Epub 2014 Mar 7. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12755/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24606326 PubMed]
+#Chong EA, Ahmadi T, Aqui NA, Svoboda J, Nasta SD, Mato AR, Walsh KM, Schuster SJ. Combination of lenalidomide and rituximab overcomes rituximab resistance in patients with indolent B-cell and mantle cell lymphomas. Clin Cancer Res. 2015 Apr 15;21(8):1835-42. Epub 2015 Jan 28. [http://clincancerres.aacrjournals.org/content/21/8/1835.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25632047 PubMed]
 <!-- # '''Abstract:''' John Leonard, Sin-Ho Jung, Jeffrey L. Johnson, Nancy Bartlett, Kristie A. Blum, Bruce D. Cheson. CALGB 50401: A randomized trial of lenalidomide alone versus lenalidomide plus rituximab in patients with recurrent follicular lymphoma. J Clin Oncol 30, 2012 (suppl; abstr 8000) [http://meetinglibrary.asco.org/content/93509-114 link to abstract] -->
-# Leonard JP, Jung SH, Johnson J, Pitcher BN, Bartlett NL, Blum KA, Czuczman M, Giguere JK, Cheson BD. Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). J Clin Oncol. 2015 Nov 1;33(31):3635-40. Epub 2015 Aug 24. [http://jco.ascopubs.org/content/33/31/3635.full link to full article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622102/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26304886 PubMed]
+#Leonard JP, Jung SH, Johnson J, Pitcher BN, Bartlett NL, Blum KA, Czuczman M, Giguere JK, Cheson BD. Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). J Clin Oncol. 2015 Nov 1;33(31):3635-40. Epub 2015 Aug 24. [http://jco.ascopubs.org/content/33/31/3635.full link to full article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622102/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26304886 PubMed]
-# '''AUGMENT:''' Leonard JP, Trneny M, Izutsu K, Fowler NH, Hong X, Zhu J, Zhang H, Offner F, Scheliga A, Nowakowski GS, Pinto A, Re F, Fogliatto LM, Scheinberg P, Flinn IW, Moreira C, Cabeçadas J, Liu D, Kalambakas S, Fustier P, Wu C, Gribben JG; AUGMENT Trial Investigators. AUGMENT: a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019 May 10;37(14):1188-1199. Epub 2019 Mar 21. [https://ascopubs.org/doi/full/10.1200/JCO.19.00010 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30897038 PubMed]
+#'''AUGMENT:''' Leonard JP, Trneny M, Izutsu K, Fowler NH, Hong X, Zhu J, Zhang H, Offner F, Scheliga A, Nowakowski GS, Pinto A, Re F, Fogliatto LM, Scheinberg P, Flinn IW, Moreira C, Cabeçadas J, Liu D, Kalambakas S, Fustier P, Wu C, Gribben JG; AUGMENT Trial Investigators. AUGMENT: a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019 May 10;37(14):1188-1199. Epub 2019 Mar 21. [https://ascopubs.org/doi/full/10.1200/JCO.19.00010 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30897038 PubMed]
 ==Obinutuzumab monotherapy {{#subobject:942df7|Regimen=1}}==
@@ Line 2,646: / Line 2,876: @@
 ===Variant #1 {{#subobject:fb6e5c|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ Sehn et al. 2015 (GAUSS)]
-|style="background-color:#1a9851"|Randomized Phase II (E-switch-ic)
+| style="background-color:#1a9851" |Randomized Phase II (E-switch-ic)
 |[[#Rituximab_monotherapy_3|Rituximab]]
-|style="background-color:#d9ef8b"|Might have superior ORR
+| style="background-color:#d9ef8b" |Might have superior ORR
 |-
 |}
 ====Chemotherapy====
 *[[Obinutuzumab (Gazyva)]] 1000 mg IV once per day on days 1, 8, 15, 22
 '''28-day course'''
 ====Subsequent treatment====
 *Patients with SD or better: Optional [[#Obinutuzumab_monotherapy_3|maintenance obinutuzumab]]
 ===Variant #2 {{#subobject:bb9813|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.bloodjournal.org/content/119/22/5126.long Salles et al. 2012 (GAUGUIN)]
-|style="background-color:#91cf61"|Phase I/II
+| style="background-color:#91cf61" |Phase I/II
 |-
 |}
@@ Line 2,676: / Line 2,908: @@
 ''Note: Dose here is that recommended by Salles et al. 2013 as having "encouraging activity with an acceptable safety profile"''
 ====Chemotherapy====
 *[[Obinutuzumab (Gazyva)]] as follows:
 **Cycle 1: 1600 mg (diluted to 10 mg/mL) IV once per day on days 1 & 7
 **Cycles 2 to 8: 800 mg IV once on day 1
 **''Initial infusion rate is 50 mg/hour. In the absence of infusion-related reactions (IRRs), the rate is then increased by 50 mg/hour every 30 minutes, up to a maximum of 400 mg/hour.''
 ====Supportive medications====
 *[[Acetaminophen (Tylenol)]] (no dose specified) PO once per infusion; 30 minutes prior to [[Obinutuzumab (Gazyva)]]
 *[[:Category:Antihistamines|Antihistamine]] (no drug or dose specified) PO once per infusion; 30 minutes prior to [[Obinutuzumab (Gazyva)]]
@@ Line 2,689: / Line 2,923: @@
 ===References===
-# '''GAUGUIN:''' Salles G, Morschhauser F, Lamy T, Milpied N, Thieblemont C, Tilly H, Bieska G, Asikanius E, Carlile D, Birkett J, Pisa P, Cartron G. Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients. Blood. 2012 May 31;119(22):5126-32. Epub 2012 Mar 19. [http://www.bloodjournal.org/content/119/22/5126.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22431570 PubMed]
-## '''Subgroup analysis:''' Morschhauser FA, Cartron G, Thieblemont C, Solal-Céligny P, Haioun C, Bouabdallah R, Feugier P, Bouabdallah K, Asikanius E, Lei G, Wenger M, Wassner-Fritsch E, Salles GA. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large B-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2912-9. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/31/23/2912.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23835718 PubMed]
+#'''GAUGUIN:''' Salles G, Morschhauser F, Lamy T, Milpied N, Thieblemont C, Tilly H, Bieska G, Asikanius E, Carlile D, Birkett J, Pisa P, Cartron G. Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients. Blood. 2012 May 31;119(22):5126-32. Epub 2012 Mar 19. [http://www.bloodjournal.org/content/119/22/5126.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22431570 PubMed]
-## '''Subgroup analysis:''' Salles GA, Morschhauser F, Solal-Céligny P, Thieblemont C, Lamy T, Tilly H, Gyan E, Lei G, Wenger M, Wassner-Fritsch E, Cartron G. Obinutuzumab (GA101) in patients with relapsed/refractory indolent non-Hodgkin lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2920-6. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/31/23/2920.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23835715 PubMed]
+##'''Subgroup analysis:''' Morschhauser FA, Cartron G, Thieblemont C, Solal-Céligny P, Haioun C, Bouabdallah R, Feugier P, Bouabdallah K, Asikanius E, Lei G, Wenger M, Wassner-Fritsch E, Salles GA. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large B-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2912-9. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/31/23/2912.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23835718 PubMed]
-## '''Subgroup analysis:''' Cartron G, de Guibert S, Dilhuydy MS, Morschhauser F, Leblond V, Dupuis J, Mahe B, Bouabdallah R, Lei G, Wenger M, Wassner-Fritsch E, Hallek M. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study. Blood. 2014 Oct 2;124(14):2196-202. Epub 2014 Aug 20. [http://www.bloodjournal.org/content/124/14/2196 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25143487 PubMed]
+##'''Subgroup analysis:''' Salles GA, Morschhauser F, Solal-Céligny P, Thieblemont C, Lamy T, Tilly H, Gyan E, Lei G, Wenger M, Wassner-Fritsch E, Cartron G. Obinutuzumab (GA101) in patients with relapsed/refractory indolent non-Hodgkin lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2920-6. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/31/23/2920.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23835715 PubMed]
+##'''Subgroup analysis:''' Cartron G, de Guibert S, Dilhuydy MS, Morschhauser F, Leblond V, Dupuis J, Mahe B, Bouabdallah R, Lei G, Wenger M, Wassner-Fritsch E, Hallek M. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study. Blood. 2014 Oct 2;124(14):2196-202. Epub 2014 Aug 20. [http://www.bloodjournal.org/content/124/14/2196 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25143487 PubMed]
 <!-- Presented in part at the American Society of Hematology 53rd Annual Meeting, San Diego, CA, December 10-13, 2011. -->
-# '''GAUSS:''' Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: final analysis of the GAUSS study. J Clin Oncol. 2015 Oct 20;33(30):3467-74. Epub 2015 Aug 17. [http://jco.ascopubs.org/content/33/30/3467.full link to original article]] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26282650 PubMed]
+#'''GAUSS:''' Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: final analysis of the GAUSS study. J Clin Oncol. 2015 Oct 20;33(30):3467-74. Epub 2015 Aug 17. [http://jco.ascopubs.org/content/33/30/3467.full link to original article]] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26282650 PubMed]
 ==R-CHOP {{#subobject:cd6d2c|Regimen=1}}==
@@ Line 2,704: / Line 2,939: @@
 ===Variant #1, 3 cycles {{#subobject:7ee3bb|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13954/abstract Illidge et al. 2016 (UK NCRI LG)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Dosing details for R-CHOP were not available in the abstract; this is a typical R-CHOP regimen.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 2,721: / Line 2,957: @@
 '''21-day cycle for 3 cycles'''
 ====Subsequent treatment====
 *[[#Ibritumomab_tiuxetan_monotherapy_5|Ibritumomab tiuxetan consolidation]]
 ===Variant #2, 6 cycles with prednisone 100 mg {{#subobject:9915f9|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.bloodjournal.org/content/108/10/3295.long Van Oers et al. 2006 (EORTC 20981)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[Follicular_lymphoma_-_historical#CHOP_2|CHOP]]
-|style="background-color:#1a9850"|Superior PFS
+| style="background-color:#1a9850" |Superior PFS
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 2,745: / Line 2,983: @@
 '''21-day cycle for 6 cycles'''
 ====Subsequent treatment====
 *Responders (PR or CR): [[#Rituximab_monotherapy.2C_extended_course_2|Rituximab maintenance]] versus [[#Observation_4|no further treatment]]
 ===Variant #3, 6 cycles with prednisone 100 mg/m<sup>2</sup> {{#subobject:820b17|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://jco.ascopubs.org/content/17/1/268.full Czuczman et al. 1999]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows:
 **Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days -6 & -1 (7 and 2 days before cycle 1 day 1)
@@ Line 2,769: / Line 3,009: @@
 ===References===
-# Czuczman MS, Grillo-López AJ, White CA, Saleh M, Gordon L, LoBuglio AF, Jonas C, Klippenstein D, Dallaire B, Varns C. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol. 1999 Jan;17(1):268-76. [http://jco.ascopubs.org/content/17/1/268.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10458242 PubMed]
-## '''Update:''' Czuczman MS, Weaver R, Alkuzweny B, Berlfein J, Grillo-López AJ. Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin's lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol. 2004 Dec 1;22(23):4711 to 6. Epub 2004 Oct 13. [http://jco.ascopubs.org/content/22/23/4711.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15483015 PubMed]
+#Czuczman MS, Grillo-López AJ, White CA, Saleh M, Gordon L, LoBuglio AF, Jonas C, Klippenstein D, Dallaire B, Varns C. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol. 1999 Jan;17(1):268-76. [http://jco.ascopubs.org/content/17/1/268.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10458242 PubMed]
-# '''EORTC 20981:''' van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van 't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27. [http://www.bloodjournal.org/content/108/10/3295.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16873669 PubMed]
+##'''Update:''' Czuczman MS, Weaver R, Alkuzweny B, Berlfein J, Grillo-López AJ. Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin's lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol. 2004 Dec 1;22(23):4711 to 6. Epub 2004 Oct 13. [http://jco.ascopubs.org/content/22/23/4711.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15483015 PubMed]
-## '''Update:''' van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. Epub 2010 May 3. [http://jco.ascopubs.org/content/28/17/2853.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903319/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20439641 PubMed]
+#'''EORTC 20981:''' van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van 't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27. [http://www.bloodjournal.org/content/108/10/3295.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16873669 PubMed]
-# Illidge TM, McKenzie HS, Mayes S, Bates A, Davies AJ, Pettengell R, Stanton L, Cozens K, Hampson G, Dive C, Zivanovic M, Tipping J, Gallop-Evans E, Radford JA, Johnson PW. Short duration immunochemotherapy followed by radioimmunotherapy consolidation is effective and well tolerated in relapsed follicular lymphoma: 5-year results from a UK National Cancer Research Institute Lymphoma Group study. Br J Haematol. 2016 Apr;173(2):274-82. Epub 2016 Feb 5. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13954/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26849853 PubMed]
+##'''Update:''' van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. Epub 2010 May 3. [http://jco.ascopubs.org/content/28/17/2853.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903319/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20439641 PubMed]
+#Illidge TM, McKenzie HS, Mayes S, Bates A, Davies AJ, Pettengell R, Stanton L, Cozens K, Hampson G, Dive C, Zivanovic M, Tipping J, Gallop-Evans E, Radford JA, Johnson PW. Short duration immunochemotherapy followed by radioimmunotherapy consolidation is effective and well tolerated in relapsed follicular lymphoma: 5-year results from a UK National Cancer Research Institute Lymphoma Group study. Br J Haematol. 2016 Apr;173(2):274-82. Epub 2016 Feb 5. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13954/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26849853 PubMed]
 ==R-FCM {{#subobject:35e1ac|Regimen=1}}==
@@ Line 2,784: / Line 3,025: @@
 ===Regimen {{#subobject:28fda|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.bloodjournal.org/content/104/10/3064.long Forstpointner et al. 2004]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[Follicular_lymphoma_-_historical#FCM|FCM]]
-|style="background-color:#91cf60"|Seems to have superior PFS
+| style="background-color:#91cf60" |Seems to have superior PFS
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day -1 (the day before FCM)
 *[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3
@@ Line 2,803: / Line 3,045: @@
 '''28-day cycle for 4 cycles'''
 ====Subsequent treatment====
 *PR or CR: [[#Rituximab_monotherapy.2C_abbreviated_course_2|Rituximab maintenance]] versus [[#Observation_4|no further treatment]]
 ===References===
-# Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Böck HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. Epub 2004 Jul 29. [http://www.bloodjournal.org/content/104/10/3064.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15284112 PubMed]
-## '''Update:''' Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group (GLSG). Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. Epub 2006 Aug 31. [http://www.bloodjournal.org/content/108/13/4003.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16946304 PubMed]
+#Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Böck HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. Epub 2004 Jul 29. [http://www.bloodjournal.org/content/104/10/3064.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15284112 PubMed]
+##'''Update:''' Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group (GLSG). Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. Epub 2006 Aug 31. [http://www.bloodjournal.org/content/108/13/4003.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16946304 PubMed]
 ==Rituximab monotherapy {{#subobject:8fecee|Regimen=1}}==
@@ Line 2,817: / Line 3,061: @@
 ===Variant #1 {{#subobject:56da8f|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00052-4/fulltext Hainsworth et al. 2014]
-|style="background-color:#1a9851"|Randomized (C)
+| style="background-color:#1a9851" |Randomized (C)
 |[[#Bevacizumab_.26_Rituximab|Bevacizumab & Rituximab]]
-|style="background-color:#fc8d59"|Seems to have inferior PFS
+| style="background-color:#fc8d59" |Seems to have inferior PFS
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows:
 **Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
@@ Line 2,837: / Line 3,082: @@
 ===Variant #2 {{#subobject:4baa29|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.bloodjournal.org/content/84/8/2457.long Maloney et al. 1994]
 | style="background-color:#ffffbe" |Phase 1, <20 pts
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[http://www.bloodjournal.org/content/90/6/2188.long Maloney et al. 1997a]
-|style="background-color:#91cf61"|Phase II (RT)
+| style="background-color:#91cf61" |Phase II (RT)
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://ascopubs.org/doi/abs/10.1200/JCO.1997.15.10.3266 Maloney et al. 1997b]
 | style="background-color:#ffffbe" |Phase 1, <20 pts
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[http://jco.ascopubs.org/content/16/8/2825.long McLaughlin et al. 1998]
-|style="background-color:#91cf61"|Phase II (RT)
+| style="background-color:#91cf61" |Phase II (RT)
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[http://jco.ascopubs.org/content/20/10/2453.long Witzig et al. 2002a]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Ibritumomab_tiuxetan_monotherapy_4|Ibritumomab tiuxetan]]
-|style="background-color:#d73027"|Inferior ORR
+| style="background-color:#d73027" |Inferior ORR
 |-
 |[http://www.bloodjournal.org/content/103/12/4416.full Ghielmini et al. 2004 (SAKK 35/98)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[http://jco.ascopubs.org/content/23/6/1088.long Hainsworth et al. 2005b]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ Sehn et al. 2015 (GAUSS)]
-|style="background-color:#1a9851"|Randomized Phase II (C)
+| style="background-color:#1a9851" |Randomized Phase II (C)
 |[[#Obinutuzumab_monotherapy_2|Obinutuzumab]]
-|style="background-color:#fee08b"|Might have inferior ORR
+| style="background-color:#fee08b" |Might have inferior ORR
 |-
 |}
 ''Note: the phase 1 described by Maloney et al. 1994 did not actually employ this dosing level, but is included here for reference purposes.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 ====Supportive medications====
 *(not explicitly mentioned in all references)
 *[[Acetaminophen (Tylenol)]] 650 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to [[Rituximab (Rituxan)]]
@@ Line 2,894: / Line 3,141: @@
 '''4-week course'''
 ====Subsequent treatment====
 *SAKK 35/98, patients with SD or better at 12 weeks: [[#Rituximab_monotherapy.2C_abbreviated_course_2|Rituximab maintenance]] versus [[#Observation_4|no further treatment]]
 *Hainsworth et al. 2005b, patients with SD or better: [[#Rituximab_monotherapy.2C_abbreviated_course_2|Rituximab maintenance]] versus re-treatment with rituximab at time of progression
@@ Line 2,900: / Line 3,148: @@
 ===Variant #3 {{#subobject:21e303|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70150-4/abstract Coiffier et al. 2011 (LYM-3001)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#VR|VR]]
-|style="background-color:#fc8d59"|Seems to have inferior PFS
+| style="background-color:#fc8d59" |Seems to have inferior PFS
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows:
 **Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 **Cycles 2 to 6: 375 mg/m<sup>2</sup> IV once on day 1
 ====Supportive medications====
 *[[Acetaminophen (Tylenol)]] 650 mg PO once per infusion; 30 minutes prior to [[Rituximab (Rituxan)]]
 *[[Diphenhydramine (Benadryl)]] 50 mg PO once per infusion; 30 minutes prior to [[Rituximab (Rituxan)]]
@@ Line 2,924: / Line 3,174: @@
 ===Variant #4 {{#subobject:5ed822|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171355/ Kahl et al. 2014 (RESORT)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Rituximab_monotherapy.2C_very_extended_course|Rituximab]]; indefinite
-|style="background-color:#ffffbf"|Did not meet primary endpoint of TTF
+| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
 |-
 |}
 ====Preceding treatment====
 *[[#Rituximab_monotherapy_2|Rituximab]]
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
@@ Line 2,943: / Line 3,196: @@
 ===References===
-# '''Phase 1:''' Maloney DG, Liles TM, Czerwinski DK, Waldichuk C, Rosenberg J, Grillo-Lopez A, Levy R. Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood. 1994 Oct 15;84(8):2457-66. [http://www.bloodjournal.org/content/84/8/2457.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7522629 PubMed]
-# Maloney DG, Grillo-López AJ, White CA, Bodkin D, Schilder RJ, Neidhart JA, Janakiraman N, Foon KA, Liles TM, Dallaire BK, Wey K, Royston I, Davis T, Levy R. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood. 1997 Sep 15;90(6):2188-95. [http://www.bloodjournal.org/content/90/6/2188.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9310469 PubMed]
+#'''Phase 1:''' Maloney DG, Liles TM, Czerwinski DK, Waldichuk C, Rosenberg J, Grillo-Lopez A, Levy R. Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood. 1994 Oct 15;84(8):2457-66. [http://www.bloodjournal.org/content/84/8/2457.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7522629 PubMed]
-# '''Phase 1:''' Maloney DG, Grillo-López AJ, Bodkin DJ, White CA, Liles TM, Royston I, Varns C, Rosenberg J, Levy R. IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma. J Clin Oncol. 1997 Oct;15(10):3266-74. [https://ascopubs.org/doi/abs/10.1200/JCO.1997.15.10.3266 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9336364 PubMed]
+#Maloney DG, Grillo-López AJ, White CA, Bodkin D, Schilder RJ, Neidhart JA, Janakiraman N, Foon KA, Liles TM, Dallaire BK, Wey K, Royston I, Davis T, Levy R. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood. 1997 Sep 15;90(6):2188-95. [http://www.bloodjournal.org/content/90/6/2188.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9310469 PubMed]
-# McLaughlin P, Grillo-López AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998 Aug;16(8):2825-33. [http://jco.ascopubs.org/content/16/8/2825.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9704735 PubMed]
+#'''Phase 1:''' Maloney DG, Grillo-López AJ, Bodkin DJ, White CA, Liles TM, Royston I, Varns C, Rosenberg J, Levy R. IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma. J Clin Oncol. 1997 Oct;15(10):3266-74. [https://ascopubs.org/doi/abs/10.1200/JCO.1997.15.10.3266 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9336364 PubMed]
-# Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, Pohlman BL, Bartlett NL, Wiseman GA, Padre N, Grillo-López AJ, Multani P, White CA. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2002 May 15;20(10):2453-63. [http://jco.ascopubs.org/content/20/10/2453.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12011122 PubMed]
+#McLaughlin P, Grillo-López AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998 Aug;16(8):2825-33. [http://jco.ascopubs.org/content/16/8/2825.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9704735 PubMed]
-# '''SAKK 35/98:''' Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. [http://www.bloodjournal.org/content/103/12/4416.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14976046 PubMed]
+#Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, Pohlman BL, Bartlett NL, Wiseman GA, Padre N, Grillo-López AJ, Multani P, White CA. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2002 May 15;20(10):2453-63. [http://jco.ascopubs.org/content/20/10/2453.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12011122 PubMed]
-## '''Update:''' Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. [http://jco.ascopubs.org/content/28/29/4480.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20697092 PubMed]
+#'''SAKK 35/98:''' Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. [http://www.bloodjournal.org/content/103/12/4416.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14976046 PubMed]
-# Hainsworth JD, Litchy S, Shaffer DW, Lackey VL, Grimaldi M, Greco FA. Maximizing therapeutic benefit of rituximab: maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin's lymphoma--a randomized phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Feb 20;23(6):1088-95. Epub 2005 Jan 18. [http://jco.ascopubs.org/content/23/6/1088.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15657401 PubMed]
+##'''Update:''' Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. [http://jco.ascopubs.org/content/28/29/4480.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20697092 PubMed]
-# Coiffier B, Osmanov EA, Hong X, Scheliga A, Mayer J, Offner F, Rule S, Teixeira A, Walewski J, de Vos S, Crump M, Shpilberg O, Esseltine DL, Zhu E, Enny C, Theocharous P, van de Velde H, Elsayed YA, Zinzani PL; LYM-3001 study investigators. Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial. Lancet Oncol. 2011 Aug;12(8):773-84. Epub 2011 Jul 1. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70150-4/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21724462 PubMed]
+#Hainsworth JD, Litchy S, Shaffer DW, Lackey VL, Grimaldi M, Greco FA. Maximizing therapeutic benefit of rituximab: maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin's lymphoma--a randomized phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Feb 20;23(6):1088-95. Epub 2005 Jan 18. [http://jco.ascopubs.org/content/23/6/1088.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15657401 PubMed]
-## '''Subgroup analysis:''' Zinzani PL, Khuageva NK, Wang H, Garicochea B, Walewski J, Van Hoof A, Soubeyran P, Caballero D, Buckstein R, Esseltine DL, Theocharous P, Enny C, Zhu E, Elsayed YA, Coiffier B. Bortezomib plus rituximab versus rituximab in patients with high-risk, relapsed, rituximab-naïve or rituximab-sensitive follicular lymphoma: subgroup analysis of a randomized phase 3 trial. J Hematol Oncol. 2012 Oct 22;5:67. [http://www.jhoonline.org/content/5/1/67 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3502148/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23088650 PubMed]
+#Coiffier B, Osmanov EA, Hong X, Scheliga A, Mayer J, Offner F, Rule S, Teixeira A, Walewski J, de Vos S, Crump M, Shpilberg O, Esseltine DL, Zhu E, Enny C, Theocharous P, van de Velde H, Elsayed YA, Zinzani PL; LYM-3001 study investigators. Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial. Lancet Oncol. 2011 Aug;12(8):773-84. Epub 2011 Jul 1. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70150-4/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21724462 PubMed]
-# '''ECOG E4402:''' Kahl BS, Hong F, Williams ME, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ. Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: Eastern Cooperative Oncology Group protocol E4402. J Clin Oncol. 2014 Oct 1;32(28):3096-102. Epub 2014 Aug 25. [http://jco.ascopubs.org/content/32/28/3096.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171355/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25154829 PubMed]
+##'''Subgroup analysis:''' Zinzani PL, Khuageva NK, Wang H, Garicochea B, Walewski J, Van Hoof A, Soubeyran P, Caballero D, Buckstein R, Esseltine DL, Theocharous P, Enny C, Zhu E, Elsayed YA, Coiffier B. Bortezomib plus rituximab versus rituximab in patients with high-risk, relapsed, rituximab-naïve or rituximab-sensitive follicular lymphoma: subgroup analysis of a randomized phase 3 trial. J Hematol Oncol. 2012 Oct 22;5:67. [http://www.jhoonline.org/content/5/1/67 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3502148/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23088650 PubMed]
-# Hainsworth JD, Greco FA, Raefsky EL, Thompson DS, Lunin S, Reeves J Jr, White L, Quinn R, DeBusk LM, Flinn IW. Rituximab with or without bevacizumab for the treatment of patients with relapsed follicular lymphoma. Clin Lymphoma Myeloma Leuk. 2014 Aug;14(4):277-83. Epub 2014 Feb 28. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00052-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24679633 PubMed]
+#'''ECOG E4402:''' Kahl BS, Hong F, Williams ME, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ. Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: Eastern Cooperative Oncology Group protocol E4402. J Clin Oncol. 2014 Oct 1;32(28):3096-102. Epub 2014 Aug 25. [http://jco.ascopubs.org/content/32/28/3096.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171355/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25154829 PubMed]
+#Hainsworth JD, Greco FA, Raefsky EL, Thompson DS, Lunin S, Reeves J Jr, White L, Quinn R, DeBusk LM, Flinn IW. Rituximab with or without bevacizumab for the treatment of patients with relapsed follicular lymphoma. Clin Lymphoma Myeloma Leuk. 2014 Aug;14(4):277-83. Epub 2014 Feb 28. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00052-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24679633 PubMed]
 <!-- Presented in part at the American Society of Hematology 53rd Annual Meeting, San Diego, CA, December 10-13, 2011. -->
-# '''GAUSS:''' Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: final analysis of the GAUSS study. J Clin Oncol. 2015 Oct 20;33(30):3467-74. Epub 2015 Aug 17. [http://jco.ascopubs.org/content/33/30/3467.full link to original article]] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26282650 PubMed]
+#'''GAUSS:''' Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: final analysis of the GAUSS study. J Clin Oncol. 2015 Oct 20;33(30):3467-74. Epub 2015 Aug 17. [http://jco.ascopubs.org/content/33/30/3467.full link to original article]] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26282650 PubMed]
 ==VR {{#subobject:eeeda9|Regimen=1}}==
@@ Line 2,967: / Line 3,221: @@
 ===Variant #1 {{#subobject:d4c970|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70150-4/abstract Coiffier et al. 2011 (LYM-3001)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#Rituximab_monotherapy_3|Rituximab]]
-|style="background-color:#91cf60"|Seems to have superior PFS
+| style="background-color:#91cf60" |Seems to have superior PFS
 |-
 |}
 ====Chemotherapy====
 *[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV over 3 to 5 seconds once per day on days 1, 8, 15, 22
 *[[Rituximab (Rituxan)]] as follows:
 **Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 **Cycles 2 to 5: 375 mg/m<sup>2</sup> IV once on day 1
 ====Supportive medications====
 *No routine antiviral prophylaxis was mandated
@@ Line 2,991: / Line 3,247: @@
 ===Variant #2 {{#subobject:c079c5|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2010.08340.x/full Agathocleous et al. 2010]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 *[[Rituximab (Rituxan)]] as follows:
@@ Line 3,007: / Line 3,264: @@
 ===Variant #3 {{#subobject:4605b4|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://jco.ascopubs.org/content/27/30/5023.long de Vos et al. 2009]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 *[[Rituximab (Rituxan)]] as follows:
@@ Line 3,023: / Line 3,281: @@
 ===Variant #4 {{#subobject:b049b0|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116936/ Baiocchi et al. 2011 (OSU-0430)]
-|style="background-color:#ffffbe"|Phase II, <20 patients reported
+| style="background-color:#ffffbe" |Phase II, <20 patients reported
 |-
 |}
@@ Line 3,033: / Line 3,291: @@
 ''Bortezomib dose was initially 1.5 mg/m<sup>2</sup> but was reduced due to excess grade 3 neurotoxicity.''
 ====Chemotherapy====
 *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
 *[[Rituximab (Rituxan)]] as follows:
@@ Line 3,039: / Line 3,298: @@
 '''21-day cycle for up to 5 cycles.'''
 ====Subsequent treatment====
 *SD or better: optional [[#VR_2|VR maintenance]]
 ===References===
-# de Vos S, Goy A, Dakhil SR, Saleh MN, McLaughlin P, Belt R, Flowers CR, Knapp M, Hart L, Patel-Donnelly D, Glenn M, Gregory SA, Holladay C, Zhang T, Boral AL. Multicenter randomized phase II study of weekly or twice-weekly bortezomib plus rituximab in patients with relapsed or refractory follicular or marginal-zone B-cell lymphoma. J Clin Oncol. 2009 Oct 20;27(30):5023-30. Epub 2009 Sep 21. [http://jco.ascopubs.org/content/27/30/5023.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19770386 PubMed]
-# Agathocleous A, Rohatiner A, Rule S, Hunter H, Kerr JP, Neeson SM, Matthews J, Strauss S, Montoto S, Johnson P, Radford J, Lister A. Weekly versus twice weekly bortezomib given in conjunction with rituximab, in patients with recurrent follicular lymphoma, mantle cell lymphoma and Waldenström macroglobulinaemia. Br J Haematol. 2010 Nov;151(4):346-53. Epub 2010 Sep 29. [https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2010.08340.x/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20880120 PubMed]
+#de Vos S, Goy A, Dakhil SR, Saleh MN, McLaughlin P, Belt R, Flowers CR, Knapp M, Hart L, Patel-Donnelly D, Glenn M, Gregory SA, Holladay C, Zhang T, Boral AL. Multicenter randomized phase II study of weekly or twice-weekly bortezomib plus rituximab in patients with relapsed or refractory follicular or marginal-zone B-cell lymphoma. J Clin Oncol. 2009 Oct 20;27(30):5023-30. Epub 2009 Sep 21. [http://jco.ascopubs.org/content/27/30/5023.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19770386 PubMed]
-# '''OSU-0430:''' Baiocchi RA, Alinari L, Lustberg ME, Lin TS, Porcu P, Li X, Johnston JS, Byrd JC, Blum KA. Phase 2 trial of rituximab and bortezomib in patients with relapsed or refractory mantle cell and follicular lymphoma. Cancer. 2011 Jun 1;117(11):2442-51. Epub 2010 Dec 14. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.25792/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116936/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24048792 PubMed]
+#Agathocleous A, Rohatiner A, Rule S, Hunter H, Kerr JP, Neeson SM, Matthews J, Strauss S, Montoto S, Johnson P, Radford J, Lister A. Weekly versus twice weekly bortezomib given in conjunction with rituximab, in patients with recurrent follicular lymphoma, mantle cell lymphoma and Waldenström macroglobulinaemia. Br J Haematol. 2010 Nov;151(4):346-53. Epub 2010 Sep 29. [https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2010.08340.x/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20880120 PubMed]
-# Coiffier B, Osmanov EA, Hong X, Scheliga A, Mayer J, Offner F, Rule S, Teixeira A, Walewski J, de Vos S, Crump M, Shpilberg O, Esseltine DL, Zhu E, Enny C, Theocharous P, van de Velde H, Elsayed YA, Zinzani PL; LYM-3001 study investigators. Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial. Lancet Oncol. 2011 Aug;12(8):773-84. Epub 2011 Jul 1. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70150-4/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21724462 PubMed]
+#'''OSU-0430:''' Baiocchi RA, Alinari L, Lustberg ME, Lin TS, Porcu P, Li X, Johnston JS, Byrd JC, Blum KA. Phase 2 trial of rituximab and bortezomib in patients with relapsed or refractory mantle cell and follicular lymphoma. Cancer. 2011 Jun 1;117(11):2442-51. Epub 2010 Dec 14. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.25792/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116936/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24048792 PubMed]
-## '''Subgroup analysis:''' Zinzani PL, Khuageva NK, Wang H, Garicochea B, Walewski J, Van Hoof A, Soubeyran P, Caballero D, Buckstein R, Esseltine DL, Theocharous P, Enny C, Zhu E, Elsayed YA, Coiffier B. Bortezomib plus rituximab versus rituximab in patients with high-risk, relapsed, rituximab-naïve or rituximab-sensitive follicular lymphoma: subgroup analysis of a randomized phase 3 trial. J Hematol Oncol. 2012 Oct 22;5:67. [http://www.jhoonline.org/content/5/1/67 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3502148/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23088650 PubMed]
+#Coiffier B, Osmanov EA, Hong X, Scheliga A, Mayer J, Offner F, Rule S, Teixeira A, Walewski J, de Vos S, Crump M, Shpilberg O, Esseltine DL, Zhu E, Enny C, Theocharous P, van de Velde H, Elsayed YA, Zinzani PL; LYM-3001 study investigators. Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial. Lancet Oncol. 2011 Aug;12(8):773-84. Epub 2011 Jul 1. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70150-4/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21724462 PubMed]
+##'''Subgroup analysis:''' Zinzani PL, Khuageva NK, Wang H, Garicochea B, Walewski J, Van Hoof A, Soubeyran P, Caballero D, Buckstein R, Esseltine DL, Theocharous P, Enny C, Zhu E, Elsayed YA, Coiffier B. Bortezomib plus rituximab versus rituximab in patients with high-risk, relapsed, rituximab-naïve or rituximab-sensitive follicular lymphoma: subgroup analysis of a randomized phase 3 trial. J Hematol Oncol. 2012 Oct 22;5:67. [http://www.jhoonline.org/content/5/1/67 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3502148/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23088650 PubMed]
 =Relapsed or refractory, non-randomized or retrospective data=
@@ Line 3,058: / Line 3,319: @@
 ===Regimen {{#subobject:b9a669|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://jco.ascopubs.org/content/23/4/676.long O'Connor et al. 2005]
-|style="background-color:#ffffbe"|Phase II, <20 patients reported
+| style="background-color:#ffffbe" |Phase II, <20 patients reported
 |-
 |}
 ====Chemotherapy====
 *[[Bortezomib (Velcade)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
 ====Supportive medications====
 *"Use of antiemetics, erythropoietin, and [[Filgrastim (Neupogen)]] was allowed if deemed necessary by the treating physician."
@@ Line 3,074: / Line 3,337: @@
 ===References===
-# O'Connor OA, Wright J, Moskowitz C, Muzzy J, MacGregor-Cortelli B, Stubblefield M, Straus D, Portlock C, Hamlin P, Choi E, Dumetrescu O, Esseltine D, Trehu E, Adams J, Schenkein D, Zelenetz AD. Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol. 2005 Feb 1;23(4):676-84. Epub 2004 Dec 21. [http://jco.ascopubs.org/content/23/4/676.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15613699 PubMed]
+#O'Connor OA, Wright J, Moskowitz C, Muzzy J, MacGregor-Cortelli B, Stubblefield M, Straus D, Portlock C, Hamlin P, Choi E, Dumetrescu O, Esseltine D, Trehu E, Adams J, Schenkein D, Zelenetz AD. Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol. 2005 Feb 1;23(4):676-84. Epub 2004 Dec 21. [http://jco.ascopubs.org/content/23/4/676.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15613699 PubMed]
 ==BVR {{#subobject:ad1aa9|Regimen=1}}==
@@ Line 3,085: / Line 3,349: @@
 ===Variant #1, 1.3/90/375 {{#subobject:a04708|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062293/ Friedberg et al. 2011]
-|style="background-color:#ffffbe"|Phase II, <20 patients in this subgroup
+| style="background-color:#ffffbe" |Phase II, <20 patients in this subgroup
 |-
 |}
 ====Chemotherapy====
 *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11, '''given first'''
 *[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 4, '''given third'''
@@ Line 3,098: / Line 3,363: @@
 ====Supportive medications====
 *Premedications, antiemetic therapy, and growth factor support per institutional guidelines
 *No routine antibiotic or antiviral prophylaxis was given
@@ Line 3,105: / Line 3,371: @@
 ===Variant #2, 1.6/90/375 {{#subobject:aff118|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://jco.ascopubs.org/content/29/25/3389.long Fowler et al. 2011 (VERTICAL)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Note: Bendamustine was dose-escalated in the first phase of the trial and the 90 mg/m<sup>2</sup> dose is the MTD.''
 ====Chemotherapy====
 *[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, '''given first'''
 *[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2, '''given second'''
 *[[Rituximab (Rituxan)]] as follows, '''given third''':
 **Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 **Cycles 2 to 5: 375 mg/m<sup>2</sup> IV once on day 1
 ====Supportive medications====
 *Antiviral prophylaxis at physician discretion
@@ Line 3,127: / Line 3,395: @@
 ===References===
 <!-- Presented in abstract form at the 51st annual meeting of the American Society of Hematology, New Orleans, LA, December 8, 2009. -->
-# Friedberg JW, Vose JM, Kelly JL, Young F, Bernstein SH, Peterson D, Rich L, Blumel S, Proia NK, Liesveld J, Fisher RI, Armitage JO, Grant S, Leonard JP. The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma. Blood. 2011 Mar 10;117(10):2807-12. Epub 2011 Jan 14. [http://www.bloodjournal.org/content/117/10/2807.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062293/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21239695 PubMed]
+#Friedberg JW, Vose JM, Kelly JL, Young F, Bernstein SH, Peterson D, Rich L, Blumel S, Proia NK, Liesveld J, Fisher RI, Armitage JO, Grant S, Leonard JP. The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma. Blood. 2011 Mar 10;117(10):2807-12. Epub 2011 Jan 14. [http://www.bloodjournal.org/content/117/10/2807.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062293/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21239695 PubMed]
 <!-- Presented at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and orally at the 51st Annual Meeting of the American Society of Hematology, December 5-8, 2009, New Orleans, LA. -->
-# '''VERTICAL:''' Fowler N, Kahl BS, Lee P, Matous JV, Cashen AF, Jacobs SA, Letzer J, Amin B, Williams ME, Smith S, Saleh A, Rosen P, Shi H, Parasuraman S, Cheson BD. Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II VERTICAL study. J Clin Oncol. 2011 Sep 1;29(25):3389-95. Epub 2011 Aug 1. [http://jco.ascopubs.org/content/29/25/3389.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21810687 PubMed]
+#'''VERTICAL:''' Fowler N, Kahl BS, Lee P, Matous JV, Cashen AF, Jacobs SA, Letzer J, Amin B, Williams ME, Smith S, Saleh A, Rosen P, Shi H, Parasuraman S, Cheson BD. Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II VERTICAL study. J Clin Oncol. 2011 Sep 1;29(25):3389-95. Epub 2011 Aug 1. [http://jco.ascopubs.org/content/29/25/3389.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21810687 PubMed]
 ==Copanlisib monotherapy {{#subobject:93db44|Regimen=1}}==
@@ Line 3,142: / Line 3,411: @@
 |}
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |CHRONOS-1 (*)
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 | style="background-color:#9ebcda" |ORR: 59% (95% CI, 49-68)
 |-
@@ Line 3,153: / Line 3,422: @@
 ''Note: this is the FDA-recommended dose and the dose used for most of the patients enrolled in this trial; however, the publication to date only details the weight-based dosing (see below).''
 ====Chemotherapy====
 *[[Copanlisib (Aliqopa)]] 60 mg IV over 60 minutes once per day on days 1, 8, 15
@@ Line 3,159: / Line 3,429: @@
 ===Variant #2, weight-based {{#subobject:f9baa2|Variant=1}}===
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834070/ Dreyling et al. 2017 (CHRONOS-1)]
-|style="background-color:#91cf61"|Phase II (RT)
+| style="background-color:#91cf61" |Phase II (RT)
 | style="background-color:#9ebcda" |ORR: 59% (95% CI, 49-68)
 |-
 |}
 ====Chemotherapy====
 *[[Copanlisib (Aliqopa)]] 0.8 mg/kg IV over 60 minutes once per day on days 1, 8, 15
@@ Line 3,174: / Line 3,445: @@
 ===References===
-# '''CHRONOS-1:''' Dreyling M, Morschhauser F, Bouabdallah K, Bron D, Cunningham D, Assouline SE, Verhoef G, Linton K, Thieblemont C, Vitolo U, Hiemeyer F, Giurescu M, Garcia-Vargas J, Gorbatchevsky I, Liu L, Koechert K, Peña C, Neves M, Childs BH, Zinzani PL. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Ann Oncol. 2017 Sep 1;28(9):2169-2178. [https://academic.oup.com/annonc/article/28/9/2169/3868097 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834070/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28633365 PubMed]
-==FR {{#subobject:abb23b|Regimen=1}}==
+#'''CHRONOS-1:''' Dreyling M, Morschhauser F, Bouabdallah K, Bron D, Cunningham D, Assouline SE, Verhoef G, Linton K, Thieblemont C, Vitolo U, Hiemeyer F, Giurescu M, Garcia-Vargas J, Gorbatchevsky I, Liu L, Koechert K, Peña C, Neves M, Childs BH, Zinzani PL. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Ann Oncol. 2017 Sep 1;28(9):2169-2178. [https://academic.oup.com/annonc/article/28/9/2169/3868097 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834070/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28633365 PubMed]
+<br />
+==Duvelisib monotherapy {{#subobject:d573d9|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-FR: '''<u>F</u>'''ludarabine & '''<u>R</u>'''ituximab
-===Regimen {{#subobject:4f5008|Variant=1}}===
+===Regimen {{#subobject:b9a669|Variant=1}}===
-{| class="wikitable" style="width: 75%; text-align:center;"
+{| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 25%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[http://jco.ascopubs.org/content/23/4/694.long Czuczman et al. 2005]
+|[https://ascopubs.org/doi/pdf/10.1200/JCO.18.00915 DYNAMO]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#ffffbe" |Phase II, 83 patients reported
-| style="background-color:#f7fcfd" |ORR: 90%
 |-
 |}
 ====Chemotherapy====
-*[[Fludarabine (Fludara)]] as follows:
-**Weeks 2, 6, 10, 14, 18, 22: 25 mg/m<sup>2</sup> IV once per day on days 1 to 5
+*[[Duvelisib (Copiktra)|Duvelisib]] 25 mg PO twice per day continuously until progression
+===References===
+#Flint IW, Miller CB, Ardeshna KM, Tetreault S, Assouline SE, Mayer J, Merli M, Lunin SD, Pettitt AR, Nagy Z, Tournilhac O, Abou-Nassar KE, Crump M, Jacobsen ED, de Vos S, Kelly VM, Shi W, Steelman L, Le N, Weaver DT, Lustgarten S, Wagner-Johnston ND, Zinzani PL. DYNAMO: A Phase II Study of Duvelisib (IPI-145) in Patients With Refractory Indolent Non-Hodgkin Lymphoma. J Clin Oncol. 2019 Apr 10;37(11):912-922. Epub 2019 Feb 11. [https://ascopubs.org/doi/pdf/10.1200/JCO.18.00915 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30742566 PubMed]
+==FR {{#subobject:abb23b|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+FR: '''<u>F</u>'''ludarabine & '''<u>R</u>'''ituximab
+===Regimen {{#subobject:4f5008|Variant=1}}===
+{| class="wikitable" style="width: 75%; text-align:center;"
+! style="width: 33%" |Study
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
+|-
+|[http://jco.ascopubs.org/content/23/4/694.long Czuczman et al. 2005]
+| style="background-color:#91cf61" |Phase II
+| style="background-color:#f7fcfd" |ORR: 90%
+|-
+|}
+====Chemotherapy====
+*[[Fludarabine (Fludara)]] as follows:
+**Weeks 2, 6, 10, 14, 18, 22: 25 mg/m<sup>2</sup> IV once per day on days 1 to 5
 *[[Rituximab (Rituxan)]] as follows:
 **Weeks 1 & 26: 375 mg/m<sup>2</sup> IV once per day on days 1 & 4
@@ Line 3,204: / Line 3,501: @@
 ===References===
-# Czuczman MS, Koryzna A, Mohr A, Stewart C, Donohue K, Blumenson L, Bernstein ZP, McCarthy P, Alam A, Hernandez-Ilizaliturri F, Skipper M, Brown K, Chanan-Khan A, Klippenstein D, Loud P, Rock MK, Benyunes M, Grillo-Lopez A, Bernstein SH. Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma. J Clin Oncol. 2005 Feb 1;23(4):694-704. [http://jco.ascopubs.org/content/23/4/694.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15681517 PubMed]
+#Czuczman MS, Koryzna A, Mohr A, Stewart C, Donohue K, Blumenson L, Bernstein ZP, McCarthy P, Alam A, Hernandez-Ilizaliturri F, Skipper M, Brown K, Chanan-Khan A, Klippenstein D, Loud P, Rock MK, Benyunes M, Grillo-Lopez A, Bernstein SH. Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma. J Clin Oncol. 2005 Feb 1;23(4):694-704. [http://jco.ascopubs.org/content/23/4/694.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15681517 PubMed]
 ==Ibrutinib monotherapy {{#subobject:ba5ba9|Regimen=1}}==
@@ Line 3,213: / Line 3,511: @@
 ===Regimen {{#subobject:f4ee96|Variant=1}}===
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[http://www.bloodjournal.org/content/131/2/182.long Bartlett et al. 2017]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |ORR: 37.5% (95% CI, 23-54)
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8853 Gopal et al. 2018 (DAWN)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |ORR: 21% (95% CI, 14-30)
 |-
 |}
 ====Chemotherapy====
 *[[Ibrutinib (Imbruvica)]] 560 mg PO once per day
@@ Line 3,233: / Line 3,532: @@
 ===References===
 <!-- # '''Abstract:''' Nancy L. Bartlett, MD, Betsy R. LaPlant, MS, Jing Qi, MD, PhD, Stephen M. Ansell, MD, PhD, John G. Kuruvilla, MD, Craig B. Reeder, MD, Lim S. Thye, MD, Daniel M. Anderson, MD, MPH, Charles Erlichman, MD and Barry A. Siegel, MD. Ibrutinib Monotherapy in Relapsed/Refractory Follicular Lymphoma (FL): Preliminary Results of a Phase 2 Consortium (P2C) Trial. Blood 2014 124:800. [http://www.bloodjournal.org/content/124/21/800 link to abstract] -->
-# Bartlett NL, Costello BA, LaPlant BR, Ansell SM, Kuruvilla JG, Reeder CB, Thye LS, Anderson DM, Krysiak K, Ramirez C, Qi J, Siegel BA, Griffith M, Griffith OL, Gomez F, Fehniger TA. Single-agent ibrutinib in relapsed or refractory follicular lymphoma: a phase 2 consortium trial. Blood. 2018 Jan 11;131(2):182-190. Epub 2017 Oct 26. [http://www.bloodjournal.org/content/131/2/182.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29074501 PubMed]
-# '''DAWN:''' Gopal AK, Schuster SJ, Fowler NH, Trotman J, Hess G, Hou JZ, Yacoub A, Lill M, Martin P, Vitolo U, Spencer A, Radford J, Jurczak W, Morton J, Caballero D, Deshpande S, Gartenberg GJ, Wang SS, Damle RN, Schaffer M, Balasubramanian S, Vermeulen J, Cheson BD, Salles G. Ibrutinib as treatment for patients with relapsed/refractory follicular lymphoma: results from the open-label, multicenter, phase II DAWN study. J Clin Oncol. 2018 Aug 10;36(23):2405-2412. Epub 2018 May 31. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8853 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29851546 PubMed]
+#Bartlett NL, Costello BA, LaPlant BR, Ansell SM, Kuruvilla JG, Reeder CB, Thye LS, Anderson DM, Krysiak K, Ramirez C, Qi J, Siegel BA, Griffith M, Griffith OL, Gomez F, Fehniger TA. Single-agent ibrutinib in relapsed or refractory follicular lymphoma: a phase 2 consortium trial. Blood. 2018 Jan 11;131(2):182-190. Epub 2017 Oct 26. [http://www.bloodjournal.org/content/131/2/182.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29074501 PubMed]
+#'''DAWN:''' Gopal AK, Schuster SJ, Fowler NH, Trotman J, Hess G, Hou JZ, Yacoub A, Lill M, Martin P, Vitolo U, Spencer A, Radford J, Jurczak W, Morton J, Caballero D, Deshpande S, Gartenberg GJ, Wang SS, Damle RN, Schaffer M, Balasubramanian S, Vermeulen J, Cheson BD, Salles G. Ibrutinib as treatment for patients with relapsed/refractory follicular lymphoma: results from the open-label, multicenter, phase II DAWN study. J Clin Oncol. 2018 Aug 10;36(23):2405-2412. Epub 2018 May 31. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.8853 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29851546 PubMed]
 ==Idelalisib monotherapy {{#subobject:7fef70|Regimen=1}}==
@@ Line 3,245: / Line 3,545: @@
 ===Regimen {{#subobject:cea36|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039496/ Gopal et al. 2014 (DELTA)]
-|style="background-color:#91cf61"|Phase II (RT)
+| style="background-color:#91cf61" |Phase II (RT)
 |-
 |}
 ====Chemotherapy====
 *[[Idelalisib (Zydelig)]] 150 mg PO twice per day
@@ Line 3,258: / Line 3,559: @@
 ===References===
-# '''DELTA:''' Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. PI3Kd inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014 Mar 13;370(11):1008-18. Epub 2014 Jan 22. [https://www.nejm.org/doi/full/10.1056/NEJMoa1314583 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039496/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24450858 PubMed]
-## '''Update:''' '''Abstract:''' Ajay K. Gopal, MD, Brad S. Kahl, MD, Sven de Vos, MD, PhD, Nina D. Wagner-Johnston, MD, Stephen J. Schuster, MD, Wojciech Jurczak, MD, PhD, Ian W. Flinn, MD, PhD, Christopher R. Flowers, MD, Peter Martin, MD, Andreas Viardot, MD, Kristie A. Blum, MD, Andre Goy, MD, Andrew Davies, BM PhD, Pier Luigi Zinzani, MD, Martin H. Dreyling, MD, PhD, Leanne M. Holes, Bess Sorensen, PhD, Wayne R. Godfrey, MD and Gilles Andre Salles, MD, PhD. Mature Follow up from a Phase 2 Study of PI3K-Delta Inhibitor Idelalisib in Patients with Double (Rituximab and Alkylating agent)-Refractory Indolent B-Cell Non-Hodgkin Lymphoma (iNHL). Blood 2014 124:1708. [http://www.bloodjournal.org/content/124/21/1708 link to abstract]
+#'''DELTA:''' Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. PI3Kd inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014 Mar 13;370(11):1008-18. Epub 2014 Jan 22. [https://www.nejm.org/doi/full/10.1056/NEJMoa1314583 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039496/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24450858 PubMed]
+##'''Update:''' '''Abstract:''' Ajay K. Gopal, MD, Brad S. Kahl, MD, Sven de Vos, MD, PhD, Nina D. Wagner-Johnston, MD, Stephen J. Schuster, MD, Wojciech Jurczak, MD, PhD, Ian W. Flinn, MD, PhD, Christopher R. Flowers, MD, Peter Martin, MD, Andreas Viardot, MD, Kristie A. Blum, MD, Andre Goy, MD, Andrew Davies, BM PhD, Pier Luigi Zinzani, MD, Martin H. Dreyling, MD, PhD, Leanne M. Holes, Bess Sorensen, PhD, Wayne R. Godfrey, MD and Gilles Andre Salles, MD, PhD. Mature Follow up from a Phase 2 Study of PI3K-Delta Inhibitor Idelalisib in Patients with Double (Rituximab and Alkylating agent)-Refractory Indolent B-Cell Non-Hodgkin Lymphoma (iNHL). Blood 2014 124:1708. [http://www.bloodjournal.org/content/124/21/1708 link to abstract]
 ==Inotuzumab ozogamicin monotherapy {{#subobject:c19383|Regimen=1}}==
@@ Line 3,268: / Line 3,570: @@
 ===Regimen {{#subobject:02a609|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/wol1/doi/10.1111/bjh.14094/full Goy et al. 2016]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Inotuzumab ozogamicin (Besponsa)]] 1.8 mg/m<sup>2</sup> IV once on day 1
@@ Line 3,281: / Line 3,584: @@
 ===References===
-# Goy A, Forero A, Wagner-Johnston N, Christopher Ehmann W, Tsai M, Hatake K, Ananthakrishnan R, Volkert A, Vandendries E, Ogura M. A phase 2 study of inotuzumab ozogamicin in patients with indolent B-cell non-Hodgkin lymphoma refractory to rituximab alone, rituximab and chemotherapy, or radioimmunotherapy. Br J Haematol. 2016 Aug;174(4):571-81. Epub 2016 Apr 22. [https://onlinelibrary.wiley.com/wol1/doi/10.1111/bjh.14094/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27101934 PubMed]
+#Goy A, Forero A, Wagner-Johnston N, Christopher Ehmann W, Tsai M, Hatake K, Ananthakrishnan R, Volkert A, Vandendries E, Ogura M. A phase 2 study of inotuzumab ozogamicin in patients with indolent B-cell non-Hodgkin lymphoma refractory to rituximab alone, rituximab and chemotherapy, or radioimmunotherapy. Br J Haematol. 2016 Aug;174(4):571-81. Epub 2016 Apr 22. [https://onlinelibrary.wiley.com/wol1/doi/10.1111/bjh.14094/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27101934 PubMed]
 ==Lenalidomide, Dexamethasone, Rituximab {{#subobject:7475e|Regimen=1}}==
@@ Line 3,290: / Line 3,594: @@
 ===Regimen {{#subobject:49372b|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.28405 Ahmadi et al. 2013]
-|style="background-color:#ffffbe"|Phase II, <20 pts in subgroup
+| style="background-color:#ffffbe" |Phase II, <20 pts in subgroup
 |-
 |}
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 10 mg PO once per day
 *[[Dexamethasone (Decadron)]] 8 mg (route not specified) once per day on days 1, 8, 15, 22
@@ Line 3,306: / Line 3,611: @@
 ===References===
-# Ahmadi T, Chong EA, Gordon A, Aqui NA, Nasta SD, Svoboda J, Mato AR, Schuster SJ. Combined lenalidomide, low-dose dexamethasone, and rituximab achieves durable responses in rituximab-resistant indolent and mantle cell lymphomas. Cancer. 2014 Jan 15;120(2):222-8. Epub 2013 Oct 7. [https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.28405 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24122387 PubMed]
+#Ahmadi T, Chong EA, Gordon A, Aqui NA, Nasta SD, Svoboda J, Mato AR, Schuster SJ. Combined lenalidomide, low-dose dexamethasone, and rituximab achieves durable responses in rituximab-resistant indolent and mantle cell lymphomas. Cancer. 2014 Jan 15;120(2):222-8. Epub 2013 Oct 7. [https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.28405 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24122387 PubMed]
 ==Ofatumumab monotherapy {{#subobject:a875bf|Regimen=1}}==
@@ Line 3,316: / Line 3,622: @@
 ===Regimen {{#subobject:ddfe7d|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.bloodjournal.org/content/111/12/5486.long Hagenbeek et al. 2008 (Hx-CD20-001)]
-|style="background-color:#91cf61"|Phase I/II
+| style="background-color:#91cf61" |Phase I/II
 |-
 |[http://www.bloodjournal.org/content/119/16/3698.long Czucman et al. 2012 (405 Study)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Note: there was no MTD determined in Hx-CD20-001.''
 ====Chemotherapy====
 *[[Ofatumumab (Arzerra)]] as follows:
 **Cycle 1: 300 mg IV once on day 1, then 1000 mg IV once per day on days 8, 15, 22
@@ Line 3,333: / Line 3,640: @@
 ====Supportive medications====
 *[[Acetaminophen (Tylenol)]] 1000 mg (no route specified) before each dose of [[Ofatumumab (Arzerra)]]
 *[[Cetirizine (Zyrtec)]] 10 mg (or equivalent) PO before each dose of [[Ofatumumab (Arzerra)]]
@@ Line 3,340: / Line 3,648: @@
 ===References===
-# '''Hx-CD20-001:''' Hagenbeek A, Gadeberg O, Johnson P, Pedersen LM, Walewski J, Hellmann A, Link BK, Robak T, Wojtukiewicz M, Pfreundschuh M, Kneba M, Engert A, Sonneveld P, Flensburg M, Petersen J, Losic N, Radford J. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. Blood. 2008 Jun 15;111(12):5486-95. Epub 2008 Apr 4. [http://www.bloodjournal.org/content/111/12/5486.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18390837 PubMed]
-# '''405 Study:''' Czuczman MS, Fayad L, Delwail V, Cartron G, Jacobsen E, Kuliczkowski K, Link BK, Pinter-Brown L, Radford J, Hellmann A, Gallop-Evans E, DiRienzo CG, Goldstein N, Gupta I, Jewell RC, Lin TS, Lisby S, Schultz M, Russell CA, Hagenbeek A; 405 Study Investigators. Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study. Blood. 2012 Apr 19;119(16):3698-704. Epub 2012 Mar 2. [http://www.bloodjournal.org/content/119/16/3698.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22389254 PubMed]
+#'''Hx-CD20-001:''' Hagenbeek A, Gadeberg O, Johnson P, Pedersen LM, Walewski J, Hellmann A, Link BK, Robak T, Wojtukiewicz M, Pfreundschuh M, Kneba M, Engert A, Sonneveld P, Flensburg M, Petersen J, Losic N, Radford J. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. Blood. 2008 Jun 15;111(12):5486-95. Epub 2008 Apr 4. [http://www.bloodjournal.org/content/111/12/5486.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18390837 PubMed]
+#'''405 Study:''' Czuczman MS, Fayad L, Delwail V, Cartron G, Jacobsen E, Kuliczkowski K, Link BK, Pinter-Brown L, Radford J, Hellmann A, Gallop-Evans E, DiRienzo CG, Goldstein N, Gupta I, Jewell RC, Lin TS, Lisby S, Schultz M, Russell CA, Hagenbeek A; 405 Study Investigators. Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study. Blood. 2012 Apr 19;119(16):3698-704. Epub 2012 Mar 2. [http://www.bloodjournal.org/content/119/16/3698.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22389254 PubMed]
 ==PEP-C {{#subobject:a10d44|Regimen=1}}==
@@ Line 3,352: / Line 3,661: @@
 ===Regimen {{#subobject:7794d|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1002/cncr.23422/full Coleman et al. 2008]
@@ Line 3,361: / Line 3,670: @@
 ====Chemotherapy, induction phase====
 *[[Prednisone (Sterapred)]] 20 mg PO once per day after breakfast
 *[[Etoposide (Vepesid)]] 50 mg PO once per day after dinner
@@ Line 3,367: / Line 3,677: @@
 ====Supportive medications====
 *[[Ondansetron (Zofran)]] (dose not specified, presumably PO) with each [[Procarbazine (Matulane)]] dose
@@ Line 3,372: / Line 3,683: @@
 ====Chemotherapy, maintenance phase====
 *Same medications and doses given per day as used in the induction phase, but the number of days per week they are used is titrated to maintain a WBC count of at least 3 x 10<sup>9</sup>/L; for example, 5 out of 7 days, every other day, once per week, etc.
 ===References===
-# '''Retrospective:''' Coleman M, Martin P, Ruan J, Furman R, Niesvizky R, Elstrom R, George P, Kaufman TP, Leonard JP. Prednisone, etoposide, procarbazine, and cyclophosphamide (PEP-C) oral combination chemotherapy regimen for recurring/refractory lymphoma: low-dose metronomic, multidrug therapy. Cancer. 2008 May 15;112(10):2228-32. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.23422/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18338745 PubMed]
+#'''Retrospective:''' Coleman M, Martin P, Ruan J, Furman R, Niesvizky R, Elstrom R, George P, Kaufman TP, Leonard JP. Prednisone, etoposide, procarbazine, and cyclophosphamide (PEP-C) oral combination chemotherapy regimen for recurring/refractory lymphoma: low-dose metronomic, multidrug therapy. Cancer. 2008 May 15;112(10):2228-32. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.23422/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18338745 PubMed]
 ==R-CVP {{#subobject:b2b476|Regimen=1}}==
@@ Line 3,385: / Line 3,698: @@
 ===Regimen {{#subobject:4d86f1|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13954/abstract Illidge et al. 2016 (UK NCRI LG)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Dosing details for R-CVP were not available in the abstract; this is a typical R-CVP regimen.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
@@ Line 3,401: / Line 3,715: @@
 '''21-day cycle for 3 cycles'''
 ====Subsequent treatment====
 *[[#Ibritumomab_tiuxetan_monotherapy_5|Ibritumomab tiuxetan consolidation]]
 ===References===
-# '''UK NCRI LG:''' Illidge TM, McKenzie HS, Mayes S, Bates A, Davies AJ, Pettengell R, Stanton L, Cozens K, Hampson G, Dive C, Zivanovic M, Tipping J, Gallop-Evans E, Radford JA, Johnson PW. Short duration immunochemotherapy followed by radioimmunotherapy consolidation is effective and well tolerated in relapsed follicular lymphoma: 5-year results from a UK National Cancer Research Institute Lymphoma Group study. Br J Haematol. 2016 Apr;173(2):274-82. Epub 2016 Feb 5. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13954/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26849853 PubMed]
+#'''UK NCRI LG:''' Illidge TM, McKenzie HS, Mayes S, Bates A, Davies AJ, Pettengell R, Stanton L, Cozens K, Hampson G, Dive C, Zivanovic M, Tipping J, Gallop-Evans E, Radford JA, Johnson PW. Short duration immunochemotherapy followed by radioimmunotherapy consolidation is effective and well tolerated in relapsed follicular lymphoma: 5-year results from a UK National Cancer Research Institute Lymphoma Group study. Br J Haematol. 2016 Apr;173(2):274-82. Epub 2016 Feb 5. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13954/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26849853 PubMed]
 ==R-DexaBEAM {{#subobject:542726|Regimen=1}}==
@@ Line 3,414: / Line 3,730: @@
 ===Regimen {{#subobject:41ae94|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full Kirschey et al. 2014]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ''Note: the dosing in the manuscript is different than below. The below are the correct doses as verified by the authors.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1 & 8
 *[[Dexamethasone (Decadron)]] 8 mg PO three times per day on days 1 to 10
@@ Line 3,432: / Line 3,749: @@
 '''3- to 4-week cycle for 2 cycles'''
 ====Subsequent treatment====
 *[[#R-BEAM.2C_then_auto_HSCT|R-BEAM with autologous hematopoietic stem cell transplant]] or [[#R-TBI.2FCy.2C_then_auto_HSCT|R-TBI/Cy with autologous hematopoietic stem cell transplant]]
 ===References===
-# Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25546611 PubMed]
+#Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25546611 PubMed]
 ==R-FND {{#subobject:f8dffd|Regimen=1}}==
@@ Line 3,445: / Line 3,764: @@
 ===Regimen {{#subobject:fb6d8|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901692/ Nastoupil et al. 2017]
@@ Line 3,458: / Line 3,777: @@
 ''Note: although this is the experimental arm of a negative study, the concurrent approach is the standard approach now.''
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] as follows:
 **Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1 & 8
@@ Line 3,467: / Line 3,787: @@
 '''28-day cycle for up to 8 cycles'''
 ====Subsequent treatment====
 *[[#Interferon_alfa-2a_monotherapy|Interferon alfa maintenance]]
 ===References===
-# '''Review:''' Hagemeister F, Cabanillas F, Coleman M, Gregory SA, Zinzani PL. The role of mitoxantrone in the treatment of indolent lymphomas. Oncologist. 2005 Feb;10(2):150-9. [http://theoncologist.alphamedpress.org/content/10/2/150.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15709217 PubMed] content property of [http://hemonc.org HemOnc.org]
-# '''Retrospective:''' Liu Q, Fayad L, Cabanillas F, Hagemeister FB, Ayers GD, Hess M, Romaguera J, Rodriguez MA, Tsimberidou AM, Verstovsek S, Younes A, Pro B, Lee MS, Ayala A, McLaughlin P. Improvement of overall and failure-free survival in stage IV follicular lymphoma: 25 years of treatment experience at The University of Texas M.D. Anderson Cancer Center. J Clin Oncol. 2006 Apr 1;24(10):1582-9. [http://jco.ascopubs.org/content/24/10/1582.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16575009 PubMed]
+#'''Review:''' Hagemeister F, Cabanillas F, Coleman M, Gregory SA, Zinzani PL. The role of mitoxantrone in the treatment of indolent lymphomas. Oncologist. 2005 Feb;10(2):150-9. [http://theoncologist.alphamedpress.org/content/10/2/150.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15709217 PubMed] content property of [http://hemonc.org HemOnc.org]
+#'''Retrospective:''' Liu Q, Fayad L, Cabanillas F, Hagemeister FB, Ayers GD, Hess M, Romaguera J, Rodriguez MA, Tsimberidou AM, Verstovsek S, Younes A, Pro B, Lee MS, Ayala A, McLaughlin P. Improvement of overall and failure-free survival in stage IV follicular lymphoma: 25 years of treatment experience at The University of Texas M.D. Anderson Cancer Center. J Clin Oncol. 2006 Apr 1;24(10):1582-9. [http://jco.ascopubs.org/content/24/10/1582.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16575009 PubMed]
 <!-- # '''Abstract:''' P. McLaughlin, M. A. Rodriguez, F. B. Hagemeister, J. Romaguera, A. H. Sarris, A. Younes, N. H. Dang, A. Goy, F. Samaniego, M. Hess et al. Stage IV indolent lymphoma: A randomized study of concurrent vs. sequential use of FND chemotherapy (fludarabine, mitoxantrone, dexamethasone) and rituximab (R) monoclonal antibody therapy, with interferon maintenance. 2003 ASCO Annual Meeting Abstract 2269. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview==abst_detail_view&confID==23&abstractID==102314 link to abstract] '''contains verified dosages'''
 # '''Abstract:''' G. E. Manoukian, F. B. Hagemeister, P. McLaughlin, L. Fayad, F. Samaniego, A. Goy, J. E. Romaguera, B. Pro, F. Cabanillas, M. A. Rodriguez. Rituximab, fludarabine, mitoxantrone, and dexamethasone (R-FND) for patients with relapsed indolent B-cell lymphoma (RIL). 2010 ASCO Annual Meeting Abstract 8078. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview==abst_detail_view&confID==74&abstractID==54087 link to abstract] '''contains verified dosages''' -->
-# Nastoupil LJ, McLaughlin P, Feng L, Neelapu SS, Samaniego F, Hagemeister FB, Ayala A, Romaguera JE, Goy AH, Neal E, Wang M, Fayad L, Fanale MA, Oki Y, Westin JR, Rodriguez MA, Cabanillas F, Fowler NH. High ten-year remission rates following rituximab, fludarabine, mitoxantrone and dexamethasone (R-FND) with interferon maintenance in indolent lymphoma: results of a randomized study. Br J Haematol. 2017 Apr;177(2):263-270. Epub 2017 Mar 24. [https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.14541 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901692/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28340281 PubMed]
+#Nastoupil LJ, McLaughlin P, Feng L, Neelapu SS, Samaniego F, Hagemeister FB, Ayala A, Romaguera JE, Goy AH, Neal E, Wang M, Fayad L, Fanale MA, Oki Y, Westin JR, Rodriguez MA, Cabanillas F, Fowler NH. High ten-year remission rates following rituximab, fludarabine, mitoxantrone and dexamethasone (R-FND) with interferon maintenance in indolent lymphoma: results of a randomized study. Br J Haematol. 2017 Apr;177(2):263-270. Epub 2017 Mar 24. [https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.14541 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901692/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28340281 PubMed]
 ==R-INO {{#subobject:f63c89|Regimen=1}}==
@@ Line 3,483: / Line 3,806: @@
 ===Regimen {{#subobject:5afbeb|Variant=1}}===
 {| class="wikitable" style="width: 75%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 33%" |Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878046/ Fayad et al. 2013 (B1931004)]
-|style="background-color:#91cf61"|Phase I/II
+| style="background-color:#91cf61" |Phase I/II
 |ORR: 87%
 |-
 |}
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 *[[Inotuzumab ozogamicin (Besponsa)]] 1.8 mg/m<sup>2</sup> IV once on day 2
@@ Line 3,499: / Line 3,823: @@
 ===References===
-# '''B1931004:''' Fayad L, Offner F, Smith MR, Verhoef G, Johnson P, Kaufman JL, Rohatiner A, Advani A, Foran J, Hess G, Coiffier B, Czuczman M, Giné E, Durrant S, Kneissl M, Luu KT, Hua SY, Boni J, Vandendries E, Dang NH. Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with rituximab. J Clin Oncol. 2013 Feb 10;31(5):573-83. Epub 2013 Jan 7. [http://jco.ascopubs.org/content/31/5/573.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878046/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23295790 PubMed]
+#'''B1931004:''' Fayad L, Offner F, Smith MR, Verhoef G, Johnson P, Kaufman JL, Rohatiner A, Advani A, Foran J, Hess G, Coiffier B, Czuczman M, Giné E, Durrant S, Kneissl M, Luu KT, Hua SY, Boni J, Vandendries E, Dang NH. Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with rituximab. J Clin Oncol. 2013 Feb 10;31(5):573-83. Epub 2013 Jan 7. [http://jco.ascopubs.org/content/31/5/573.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878046/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23295790 PubMed]
 ==Temsirolimus monotherapy {{#subobject:934c01|Regimen=1}}==
@@ Line 3,509: / Line 3,834: @@
 ===Regimen {{#subobject:4882ef|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020703/ Smith et al. 2010]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes once per day on days 1, 8, 15, 22
@@ Line 3,522: / Line 3,848: @@
 ===References===
-# Smith SM, van Besien K, Karrison T, Dancey J, McLaughlin P, Younes A, Smith S, Stiff P, Lester E, Modi S, Doyle LA, Vokes EE, Pro B. Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: The University of Chicago phase II consortium. J Clin Oncol. 2010 Nov 1;28(31):4740-6. Epub 2010 Sep 13. [http://jco.ascopubs.org/content/28/31/4740.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020703/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20837940 PubMed]
+#Smith SM, van Besien K, Karrison T, Dancey J, McLaughlin P, Younes A, Smith S, Stiff P, Lester E, Modi S, Doyle LA, Vokes EE, Pro B. Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: The University of Chicago phase II consortium. J Clin Oncol. 2010 Nov 1;28(31):4740-6. Epub 2010 Sep 13. [http://jco.ascopubs.org/content/28/31/4740.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020703/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20837940 PubMed]
 ==Vorinostat monotherapy {{#subobject:29c647|Regimen=1}}==
@@ Line 3,532: / Line 3,859: @@
 ===Regimen {{#subobject:f0bd7f|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083875/ Kirschbaum et al. 2011]
-|style="background-color:#ffffbe"|Phase II, <20 pts in subgroup
+| style="background-color:#ffffbe" |Phase II, <20 pts in subgroup
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282031/ Ogura et al. 2014]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Vorinostat (Zolinza)]] 200 mg PO twice per day on days 1 to 14
@@ Line 3,548: / Line 3,876: @@
 ===References===
-# Kirschbaum M, Frankel P, Popplewell L, Zain J, Delioukina M, Pullarkat V, Matsuoka D, Pulone B, Rotter AJ, Espinoza-Delgado I, Nademanee A, Forman SJ, Gandara D, Newman E. Phase II study of vorinostat for treatment of relapsed or refractory indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol. 2011 Mar 20;29(9):1198-203. Epub 2011 Feb 7. [http://jco.ascopubs.org/content/29/9/1198.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083875/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21300924 PubMed]
-# Ogura M, Ando K, Suzuki T, Ishizawa K, Oh SY, Itoh K, Yamamoto K, Au WY, Tien HF, Matsuno Y, Terauchi T, Yamamoto K, Mori M, Tanaka Y, Shimamoto T, Tobinai K, Kim WS. A multicentre phase II study of vorinostat in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma. Br J Haematol. 2014 Jun;165(6):768-776. Epub 2014 Mar 12. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12819/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282031/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24617454 PubMed]
+#Kirschbaum M, Frankel P, Popplewell L, Zain J, Delioukina M, Pullarkat V, Matsuoka D, Pulone B, Rotter AJ, Espinoza-Delgado I, Nademanee A, Forman SJ, Gandara D, Newman E. Phase II study of vorinostat for treatment of relapsed or refractory indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol. 2011 Mar 20;29(9):1198-203. Epub 2011 Feb 7. [http://jco.ascopubs.org/content/29/9/1198.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083875/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21300924 PubMed]
+#Ogura M, Ando K, Suzuki T, Ishizawa K, Oh SY, Itoh K, Yamamoto K, Au WY, Tien HF, Matsuno Y, Terauchi T, Yamamoto K, Mori M, Tanaka Y, Shimamoto T, Tobinai K, Kim WS. A multicentre phase II study of vorinostat in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma. Br J Haematol. 2014 Jun;165(6):768-776. Epub 2014 Mar 12. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12819/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282031/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24617454 PubMed]
 ==Vorinostat & Rituximab {{#subobject:bb981e|Regimen=1}}==
@@ Line 3,559: / Line 3,888: @@
 ===Regimen {{#subobject:981cd2|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349274/ Chen et al. 2015 (CoH 07195)]
-|style="background-color:#ffffbe"|Phase II, <20 patients in this subgroup
+| style="background-color:#ffffbe" |Phase II, <20 patients in this subgroup
 |-
 |}
 ====Chemotherapy====
 *[[Vorinostat (Zolinza)]] 200 mg PO twice per day on days 1 to 14
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 3,573: / Line 3,903: @@
 ===References===
-# '''CoH 07195:''' Chen R, Frankel P, Popplewell L, Siddiqi T, Ruel N, Rotter A, Thomas SH, Mott M, Nathwani N, Htut M, Nademanee A, Forman SJ, Kirschbaum M. A phase II study of vorinostat and rituximab for treatment of newly diagnosed and relapsed/refractory indolent non-Hodgkin lymphoma. Haematologica. 2015 Mar;100(3):357-62. Epub 2015 Jan 16. [http://www.haematologica.org/content/100/3/357.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349274/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25596263 PubMed]
+#'''CoH 07195:''' Chen R, Frankel P, Popplewell L, Siddiqi T, Ruel N, Rotter A, Thomas SH, Mott M, Nathwani N, Htut M, Nademanee A, Forman SJ, Kirschbaum M. A phase II study of vorinostat and rituximab for treatment of newly diagnosed and relapsed/refractory indolent non-Hodgkin lymphoma. Haematologica. 2015 Mar;100(3):357-62. Epub 2015 Jan 16. [http://www.haematologica.org/content/100/3/357.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349274/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25596263 PubMed]
 ==VR-CP {{#subobject:d1f835|Regimen=1}}==
@@ Line 3,583: / Line 3,914: @@
 ===Regimen {{#subobject:8d1a0b|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.12991/full Craig et al. 2014 (C05012)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Chemotherapy====
 *[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1 & 8
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 3,597: / Line 3,929: @@
 ====Supportive medications====
 *Antiviral prophylaxis against VZV recommended for all patients
@@ Line 3,602: / Line 3,935: @@
 ===References===
-# '''C05012:''' Craig M, Hanna WT, Cabanillas F, Chen CS, Esseltine DL, Neuwirth R, O'Connor OA. Phase II study of bortezomib in combination with rituximab, cyclophosphamide and prednisone with or without doxorubicin followed by rituximab maintenance in patients with relapsed or refractory follicular lymphoma. Br J Haematol. 2014 Sep;166(6):920-8. Epub 2014 Jul 9. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12991/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25039282 PubMed]
+#'''C05012:''' Craig M, Hanna WT, Cabanillas F, Chen CS, Esseltine DL, Neuwirth R, O'Connor OA. Phase II study of bortezomib in combination with rituximab, cyclophosphamide and prednisone with or without doxorubicin followed by rituximab maintenance in patients with relapsed or refractory follicular lymphoma. Br J Haematol. 2014 Sep;166(6):920-8. Epub 2014 Jul 9. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12991/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25039282 PubMed]
 =Consolidation after subsequent lines of therapy=
@@ Line 3,614: / Line 3,948: @@
 ===Regimen {{#subobject:4f0684|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.bloodjournal.org/content/98/13/3595.long Khouri et al. 2001]
@@ Line 3,623: / Line 3,957: @@
 {{#lst:Allogeneic HSCT|4f0684}}
 ====Immunotherapy====
 *[[Allogeneic stem cells]]
 '''Stem cells transfused on day 0'''
 ===References===
-# Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB, Korbling M, Younes A, Ippoliti C, Gajewski JL, McLaughlin P, Anderlini P, Donato ML, Cabanillas FF, Champlin RE. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood. 2001 Dec 15;98(13):3595-9. [http://www.bloodjournal.org/content/98/13/3595.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11739162 PubMed]
-## '''Update:''' Khouri IF, McLaughlin P, Saliba RM, Hosing C, Korbling M, Lee MS, Medeiros LJ, Fayad L, Samaniego F, Alousi A, Anderlini P, Couriel D, de Lima M, Giralt S, Neelapu SS, Ueno NT, Samuels BI, Hagemeister F, Kwak LW, Champlin RE. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood. 2008 Jun 15;111(12):5530-6. Epub 2008 Apr 14. Erratum in: Blood. 2009 Feb 12;113(7):1613. [http://www.bloodjournal.org/content/111/12/5530.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624452/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18411419 PubMed]
+#Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB, Korbling M, Younes A, Ippoliti C, Gajewski JL, McLaughlin P, Anderlini P, Donato ML, Cabanillas FF, Champlin RE. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood. 2001 Dec 15;98(13):3595-9. [http://www.bloodjournal.org/content/98/13/3595.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11739162 PubMed]
-## '''Update:''' Khouri IF, Saliba RM, Erwin WD, Samuels BI, Korbling M, Medeiros LJ, Valverde R, Alousi AM, Anderlini P, Bashir Q, Ciurea S, Gulbis AM, de Lima M, Hosing C, Kebriaei P, Popat UR, Fowler N, Neelapu SS, Samaniego F, Champlin RE, Macapinlac HA. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood. 2012 Jun 28;119(26):6373-8. Epub 2012 May 14. [http://www.bloodjournal.org/content/119/26/6373.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347306/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22586182 PubMed]
+##'''Update:''' Khouri IF, McLaughlin P, Saliba RM, Hosing C, Korbling M, Lee MS, Medeiros LJ, Fayad L, Samaniego F, Alousi A, Anderlini P, Couriel D, de Lima M, Giralt S, Neelapu SS, Ueno NT, Samuels BI, Hagemeister F, Kwak LW, Champlin RE. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood. 2008 Jun 15;111(12):5530-6. Epub 2008 Apr 14. Erratum in: Blood. 2009 Feb 12;113(7):1613. [http://www.bloodjournal.org/content/111/12/5530.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624452/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18411419 PubMed]
+##'''Update:''' Khouri IF, Saliba RM, Erwin WD, Samuels BI, Korbling M, Medeiros LJ, Valverde R, Alousi AM, Anderlini P, Bashir Q, Ciurea S, Gulbis AM, de Lima M, Hosing C, Kebriaei P, Popat UR, Fowler N, Neelapu SS, Samaniego F, Champlin RE, Macapinlac HA. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood. 2012 Jun 28;119(26):6373-8. Epub 2012 May 14. [http://www.bloodjournal.org/content/119/26/6373.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347306/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22586182 PubMed]
 ==Ibritumomab tiuxetan monotherapy {{#subobject:0d2dce|Regimen=1}}==
@@ Line 3,637: / Line 3,974: @@
 ===Regimen {{#subobject:bdf405|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13954/abstract Illidge et al. 2016 (UK NCRI LG)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Preceding treatment====
 *[[#R-CHOP_2|R-CHOP]] x 3 or [[#R-CVP_2|R-CVP]] x 3
 ====Radioimmunotherapy====
 *[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] 15 MBq/kg (maximum dose of 1200 MBq) IV once on day 8, '''given immediately after rituximab'''
+*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 15 MBq/kg (maximum dose of 1200 MBq) IV once on day 8, '''given immediately after rituximab'''
 '''8-day course'''
 ===References===
-# '''UK NCRI LG:''' Illidge TM, McKenzie HS, Mayes S, Bates A, Davies AJ, Pettengell R, Stanton L, Cozens K, Hampson G, Dive C, Zivanovic M, Tipping J, Gallop-Evans E, Radford JA, Johnson PW. Short duration immunochemotherapy followed by radioimmunotherapy consolidation is effective and well tolerated in relapsed follicular lymphoma: 5-year results from a UK National Cancer Research Institute Lymphoma Group study. Br J Haematol. 2016 Apr;173(2):274-82. Epub 2016 Feb 5. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13954/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26849853 PubMed]
+#'''UK NCRI LG:''' Illidge TM, McKenzie HS, Mayes S, Bates A, Davies AJ, Pettengell R, Stanton L, Cozens K, Hampson G, Dive C, Zivanovic M, Tipping J, Gallop-Evans E, Radford JA, Johnson PW. Short duration immunochemotherapy followed by radioimmunotherapy consolidation is effective and well tolerated in relapsed follicular lymphoma: 5-year results from a UK National Cancer Research Institute Lymphoma Group study. Br J Haematol. 2016 Apr;173(2):274-82. Epub 2016 Feb 5. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13954/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26849853 PubMed]
 ==Observation==
@@ Line 3,663: / Line 4,004: @@
 ===Regimen===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.bloodjournal.org/content/103/12/4416.full Ghielmini et al. 2004 (SAKK 35/98)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Rituximab_monotherapy.2C_abbreviated_course_2|Rituximab]]
-|style="background-color:#fc8d59"|Seems to have inferior EFS
+| style="background-color:#fc8d59" |Seems to have inferior EFS
 |-
 |[http://www.bloodjournal.org/content/104/10/3064.long Forstpointner et al. 2004]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Rituximab_monotherapy.2C_abbreviated_course_2|Rituximab]]
-|style="background-color:#fc8d59"|Seems to have inferior PFS
+| style="background-color:#fc8d59" |Seems to have inferior PFS
 |-
 |[http://www.bloodjournal.org/content/108/10/3295.long Van Oers et al. 2006 (EORTC 20981)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Rituximab_monotherapy.2C_extended_course_2|Rituximab]]
-|style="background-color:#fc8d59"|Seems to have inferior OS
+| style="background-color:#fc8d59" |Seems to have inferior OS
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.2012.47.1862 Pettengell et al. 2013 (EBMT Lym-1)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Rituximab_monotherapy.2C_abbreviated_course_2|Rituximab]]
-|style="background-color:#fc8d59"|Seems to have inferior PFS
+| style="background-color:#fc8d59" |Seems to have inferior PFS
 |-
 |}
 ''No further treatment after second-line therapy.''
 ====Preceding treatment====
 *SAKK 35/98: [[#Rituximab_monotherapy_3|R]] x 4
 *Forstpointner et al. 2004: [[#R-FCM_2|R-FCM]] x 4 versus [[Follicular_lymphoma_-_historical#FCM|FCM]] x 4
 *EORTC 20981: [[Follicular_lymphoma_-_historical#CHOP_2|CHOP]] versus [[#R-CHOP_2|R-CHOP]]
 *EBMT Lym-1: BEAM with auto HSCT
 ===References===
-# '''SAKK 35/98:''' Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. [http://www.bloodjournal.org/content/103/12/4416.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14976046 PubMed]
-## '''Update:''' Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. [http://jco.ascopubs.org/content/28/29/4480.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20697092 PubMed]
+#'''SAKK 35/98:''' Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. [http://www.bloodjournal.org/content/103/12/4416.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14976046 PubMed]
-# Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Böck HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. Epub 2004 Jul 29. [http://www.bloodjournal.org/content/104/10/3064.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15284112 PubMed]
+##'''Update:''' Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. [http://jco.ascopubs.org/content/28/29/4480.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20697092 PubMed]
-## '''Update:''' Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group (GLSG). Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. Epub 2006 Aug 31. [http://www.bloodjournal.org/content/108/13/4003.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16946304 PubMed]
+#Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Böck HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. Epub 2004 Jul 29. [http://www.bloodjournal.org/content/104/10/3064.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15284112 PubMed]
-# '''EORTC 20981:''' van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van 't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27. [http://www.bloodjournal.org/content/108/10/3295.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16873669 PubMed]
+##'''Update:''' Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group (GLSG). Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. Epub 2006 Aug 31. [http://www.bloodjournal.org/content/108/13/4003.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16946304 PubMed]
-## '''Update:''' van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. Epub 2010 May 3. [http://jco.ascopubs.org/content/28/17/2853.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903319/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20439641 PubMed]
+#'''EORTC 20981:''' van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van 't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27. [http://www.bloodjournal.org/content/108/10/3295.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16873669 PubMed]
-# '''EBMT Lym-1:''' Pettengell R, Schmitz N, Gisselbrecht C, Smith G, Patton WN, Metzner B, Caballero D, Tilly H, Walewski JA, Bence-Bruckler I, To B, Geisler CH, Schots R, Kimby E, Taverna CJ, Kozák T, Dreger P, Uddin R, Ruiz de Elvira C, Goldstone AH. Rituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma: a prospective randomized trial from the lymphoma working party of the European group for blood and marrow transplantation. J Clin Oncol. 2013 May 1;31(13):1624-30. Epub 2013 Apr 1. [https://ascopubs.org/doi/full/10.1200/JCO.2012.47.1862 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23547078 PubMed]
+##'''Update:''' van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. Epub 2010 May 3. [http://jco.ascopubs.org/content/28/17/2853.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903319/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20439641 PubMed]
+#'''EBMT Lym-1:''' Pettengell R, Schmitz N, Gisselbrecht C, Smith G, Patton WN, Metzner B, Caballero D, Tilly H, Walewski JA, Bence-Bruckler I, To B, Geisler CH, Schots R, Kimby E, Taverna CJ, Kozák T, Dreger P, Uddin R, Ruiz de Elvira C, Goldstone AH. Rituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma: a prospective randomized trial from the lymphoma working party of the European group for blood and marrow transplantation. J Clin Oncol. 2013 May 1;31(13):1624-30. Epub 2013 Apr 1. [https://ascopubs.org/doi/full/10.1200/JCO.2012.47.1862 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23547078 PubMed]
 ==Rituximab monotherapy, abbreviated course {{#subobject:10e39b|Regimen=1}}==
@@ Line 3,712: / Line 4,056: @@
 ===Variant #1, 4 doses {{#subobject:dfa3f2|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.bloodjournal.org/content/103/12/4416.full Ghielmini et al. 2004 (SAKK 35/98)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#Observation_4|Observation]]
-|style="background-color:#91cf60"|Seems to have superior EFS
+| style="background-color:#91cf60" |Seems to have superior EFS
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.2012.47.1862 Pettengell et al. 2013 (EBMT Lym-1)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#Observation_4|Observation]]
-|style="background-color:#91cf60"|Seems to have superior EFS
+| style="background-color:#91cf60" |Seems to have superior EFS
 |-
 |}
 ''Note: SAKK 35/98 specifies that treatment is to be given at week 12, month 5, 7, 9. Pettengell et al. 2013 does not specify when the maintenance rituximab is to begin post-auto HSCT.''
 ====Preceding treatment====
 *SAKK 35/98: [[#Rituximab_monotherapy_3|Rituximab re-induction]]
 *EBMT Lym-1: BEAM with auto HSCT
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 3,740: / Line 4,086: @@
 ===Variant #2, 8 doses {{#subobject:eca645|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.bloodjournal.org/content/104/10/3064.long Forstpointner et al. 2004]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#Observation_4|Observation]]
-|style="background-color:#91cf60"|Seems to have superior PFS
+| style="background-color:#91cf60" |Seems to have superior PFS
 |-
 |}
 ''Note: first cycle begins 3 months after completion of salvage therapy.''
 ====Preceding treatment====
 *[[#R-FCM_2|R-FCM]] x 4 versus [[Follicular_lymphoma_-_historical#FCM|FCM]] x 4
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
@@ Line 3,760: / Line 4,109: @@
 ===References===
-# '''SAKK 35/98:''' Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. [http://www.bloodjournal.org/content/103/12/4416.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14976046 PubMed]
-## '''Update:''' Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. [http://jco.ascopubs.org/content/28/29/4480.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20697092 PubMed]
+#'''SAKK 35/98:''' Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. [http://www.bloodjournal.org/content/103/12/4416.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14976046 PubMed]
-# Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Böck HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. Epub 2004 Jul 29. [http://www.bloodjournal.org/content/104/10/3064.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15284112 PubMed]
+##'''Update:''' Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. [http://jco.ascopubs.org/content/28/29/4480.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20697092 PubMed]
-## '''Update:''' Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group (GLSG). Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. Epub 2006 Aug 31. [http://www.bloodjournal.org/content/108/13/4003.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16946304 PubMed]
+#Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Böck HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. Epub 2004 Jul 29. [http://www.bloodjournal.org/content/104/10/3064.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15284112 PubMed]
-# '''EBMT Lym-1:''' Pettengell R, Schmitz N, Gisselbrecht C, Smith G, Patton WN, Metzner B, Caballero D, Tilly H, Walewski JA, Bence-Bruckler I, To B, Geisler CH, Schots R, Kimby E, Taverna CJ, Kozák T, Dreger P, Uddin R, Ruiz de Elvira C, Goldstone AH. Rituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma: a prospective randomized trial from the lymphoma working party of the European group for blood and marrow transplantation. J Clin Oncol. 2013 May 1;31(13):1624-30. Epub 2013 Apr 1. [https://ascopubs.org/doi/full/10.1200/JCO.2012.47.1862 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23547078 PubMed]
+##'''Update:''' Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group (GLSG). Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. Epub 2006 Aug 31. [http://www.bloodjournal.org/content/108/13/4003.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16946304 PubMed]
+#'''EBMT Lym-1:''' Pettengell R, Schmitz N, Gisselbrecht C, Smith G, Patton WN, Metzner B, Caballero D, Tilly H, Walewski JA, Bence-Bruckler I, To B, Geisler CH, Schots R, Kimby E, Taverna CJ, Kozák T, Dreger P, Uddin R, Ruiz de Elvira C, Goldstone AH. Rituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma: a prospective randomized trial from the lymphoma working party of the European group for blood and marrow transplantation. J Clin Oncol. 2013 May 1;31(13):1624-30. Epub 2013 Apr 1. [https://ascopubs.org/doi/full/10.1200/JCO.2012.47.1862 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23547078 PubMed]
 ==R-BEAM, then auto HSCT {{#subobject:8b88db|Regimen=1}}==
@@ Line 3,774: / Line 4,124: @@
 ===Regimen {{#subobject:77f5a0|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full Kirschey et al. 2014]
@@ Line 3,783: / Line 4,133: @@
 ''A minimum number of 2 × 10<sup>6</sup>/kg bw CD34-positive cells were required to proceed.''
 ====Preceding treatment====
 *[[#R-DexaBEAM|R-DexaBEAM]] x 2
 {{#lst:Autologous HSCT conditioning regimens|77f5a0}}
 ===References===
-# Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25546611 PubMed]
+#Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25546611 PubMed]
 ==R-TBI/Cy, then auto HSCT {{#subobject:38a16a|Regimen=1}}==
@@ Line 3,796: / Line 4,148: @@
 ===Regimen {{#subobject:1b28ce|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full Kirschey et al. 2014]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Preceding treatment====
 *[[#R-DexaBEAM|R-DexaBEAM]] x 2
 {{#lst:Autologous HSCT|785614}}
 '''Stem cells reinfused on day 0'''
 ===References===
-# Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25546611 PubMed]
+#Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13234/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25546611 PubMed]
 ==Cyclophosphamide & TBI, then auto HSCT {{#subobject:0a4915|Regimen=1}}==
@@ Line 3,818: / Line 4,172: @@
 ===Regimen {{#subobject:a2b2d3|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[https://ascopubs.org/doi/full/10.1200/JCO.2003.10.023 Schouten et al. 2003 (CUP)]
@@ Line 3,831: / Line 4,185: @@
 {{#lst:Autologous HSCT|a2b2d3}}
 ===References===
-# '''CUP:''' Schouten HC, Qian W, Kvaloy S, Porcellini A, Hagberg H, Johnsen HE, Doorduijn JK, Sydes MR, Kvalheim G. High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial. J Clin Oncol. 2003 Nov 1;21(21):3918-27. Epub 2003 Sep 29. [https://ascopubs.org/doi/full/10.1200/JCO.2003.10.023 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14517188 PubMed]
+#'''CUP:''' Schouten HC, Qian W, Kvaloy S, Porcellini A, Hagberg H, Johnsen HE, Doorduijn JK, Sydes MR, Kvalheim G. High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial. J Clin Oncol. 2003 Nov 1;21(21):3918-27. Epub 2003 Sep 29. [https://ascopubs.org/doi/full/10.1200/JCO.2003.10.023 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14517188 PubMed]
 ==(90)YFC, then allo HSCT {{#subobject:ed22a7|Regimen=1}}==
@@ Line 3,842: / Line 4,197: @@
 ===Regimen {{#subobject:efc342|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://www.bloodjournal.org/content/98/13/3595.long Khouri et al. 2001]
@@ Line 3,851: / Line 4,206: @@
 {{#lst:Allogeneic HSCT|efc342}}
 ====Immunotherapy====
 *[[Allogeneic stem cells]]
 '''Stem cells transfused on day 0'''
 ===References===
-# Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB, Korbling M, Younes A, Ippoliti C, Gajewski JL, McLaughlin P, Anderlini P, Donato ML, Cabanillas FF, Champlin RE. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood. 2001 Dec 15;98(13):3595-9. [http://www.bloodjournal.org/content/98/13/3595.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11739162 PubMed]
-## '''Update:''' Khouri IF, McLaughlin P, Saliba RM, Hosing C, Korbling M, Lee MS, Medeiros LJ, Fayad L, Samaniego F, Alousi A, Anderlini P, Couriel D, de Lima M, Giralt S, Neelapu SS, Ueno NT, Samuels BI, Hagemeister F, Kwak LW, Champlin RE. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood. 2008 Jun 15;111(12):5530-6. Epub 2008 Apr 14. Erratum in: Blood. 2009 Feb 12;113(7):1613. [http://www.bloodjournal.org/content/111/12/5530.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624452/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18411419 PubMed]
+#Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB, Korbling M, Younes A, Ippoliti C, Gajewski JL, McLaughlin P, Anderlini P, Donato ML, Cabanillas FF, Champlin RE. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood. 2001 Dec 15;98(13):3595-9. [http://www.bloodjournal.org/content/98/13/3595.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11739162 PubMed]
-## '''Update:''' Khouri IF, Saliba RM, Erwin WD, Samuels BI, Korbling M, Medeiros LJ, Valverde R, Alousi AM, Anderlini P, Bashir Q, Ciurea S, Gulbis AM, de Lima M, Hosing C, Kebriaei P, Popat UR, Fowler N, Neelapu SS, Samaniego F, Champlin RE, Macapinlac HA. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood. 2012 Jun 28;119(26):6373-8. Epub 2012 May 14. [http://www.bloodjournal.org/content/119/26/6373.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347306/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22586182 PubMed]
+##'''Update:''' Khouri IF, McLaughlin P, Saliba RM, Hosing C, Korbling M, Lee MS, Medeiros LJ, Fayad L, Samaniego F, Alousi A, Anderlini P, Couriel D, de Lima M, Giralt S, Neelapu SS, Ueno NT, Samuels BI, Hagemeister F, Kwak LW, Champlin RE. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood. 2008 Jun 15;111(12):5530-6. Epub 2008 Apr 14. Erratum in: Blood. 2009 Feb 12;113(7):1613. [http://www.bloodjournal.org/content/111/12/5530.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624452/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18411419 PubMed]
+##'''Update:''' Khouri IF, Saliba RM, Erwin WD, Samuels BI, Korbling M, Medeiros LJ, Valverde R, Alousi AM, Anderlini P, Bashir Q, Ciurea S, Gulbis AM, de Lima M, Hosing C, Kebriaei P, Popat UR, Fowler N, Neelapu SS, Samaniego F, Champlin RE, Macapinlac HA. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood. 2012 Jun 28;119(26):6373-8. Epub 2012 May 14. [http://www.bloodjournal.org/content/119/26/6373.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347306/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22586182 PubMed]
 =Maintenance after subsequent lines of therapy=
@@ Line 3,867: / Line 4,225: @@
 ===Regimen {{#subobject:ca30fc|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.12755/full Tuscano et al. 2014]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
 ====Preceding treatment====
 *[[#Lenalidomide_.26_Rituximab_3|Lenalidomide & Rituximab]]
 ====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 ====Supportive medications====
 *[[Aspirin]] 81 mg PO once per day
@@ Line 3,885: / Line 4,247: @@
 ===References===
-# Tuscano JM, Dutia M, Chee K, Brunson A, Reed-Pease C, Abedi M, Welborn J, O'Donnell RT. Lenalidomide plus rituximab can produce durable clinical responses in patients with relapsed or refractory, indolent non-Hodgkin lymphoma. Br J Haematol. 2014 May;165(3):375-81. Epub 2014 Mar 7. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12755/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24606326 PubMed]
+#Tuscano JM, Dutia M, Chee K, Brunson A, Reed-Pease C, Abedi M, Welborn J, O'Donnell RT. Lenalidomide plus rituximab can produce durable clinical responses in patients with relapsed or refractory, indolent non-Hodgkin lymphoma. Br J Haematol. 2014 May;165(3):375-81. Epub 2014 Mar 7. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.12755/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24606326 PubMed]
 ==Obinutuzumab monotherapy {{#subobject:0c3223|Regimen=1}}==
@@ Line 3,895: / Line 4,258: @@
 ===Regimen {{#subobject:c2b00c|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ Sehn et al. 2015 (GAUSS)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30097-3/fulltext Sehn et al. 2016 (GADOLIN)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
 ====Preceding treatment====
 *GAUSS: [[#Obinutuzumab_monotherapy_2|Obinutuzumab induction]]
 *GADOLIN: [[#Bendamustine_.26_Obinutuzumab_2|Bendamustine & Obinutuzumab]] x 6
 ====Chemotherapy====
 *[[Obinutuzumab (Gazyva)]] 1000 mg IV once on day 1
@@ Line 3,915: / Line 4,281: @@
 ===References===
 <!-- Presented in part at the American Society of Hematology 53rd Annual Meeting, San Diego, CA, December 10-13, 2011. -->
-# '''GAUSS:''' Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: final analysis of the GAUSS study. J Clin Oncol. 2015 Oct 20;33(30):3467-74. Epub 2015 Aug 17. [http://jco.ascopubs.org/content/33/30/3467.full link to original article]] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26282650 PubMed]
+#'''GAUSS:''' Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: final analysis of the GAUSS study. J Clin Oncol. 2015 Oct 20;33(30):3467-74. Epub 2015 Aug 17. [http://jco.ascopubs.org/content/33/30/3467.full link to original article]] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26282650 PubMed]
 <!-- # '''Abstract:''' Laurie Helen Sehn, Neil Sun Chua, Jiri Mayer, Gregory Scott Dueck, Marek Trněný, Kamal Bouabdallah, Nathan Hale Fowler, Vincent Delwail, Oliver W. Press, Gilles A. Salles, John G. Gribben, Anne Lennard, Pieternella J. Lugtenburg, Natalie Franklin, Elisabeth Wassner Fritsch, Guenter Fingerle-Rowson, Bruce D. Cheson. GADOLIN: Primary results from a phase III study of obinutuzumab plus bendamustine compared with bendamustine alone in patients with rituximab-refractory indolent non-Hodgkin lymphoma. J Clin Oncol 33, 2015 (suppl; abstr LBA8502) [http://meetinglibrary.asco.org/content/147837-156 link to abstract] -->
-# '''GADOLIN:''' Sehn LH, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben J, Lennard A, Lugtenburg PJ, Dimier N, Wassner-Fritsch E, Fingerle-Rowson G, Cheson BD. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1081-93. Epub 2016 Jun 23. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30097-3/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27345636 PubMed]
+#'''GADOLIN:''' Sehn LH, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben J, Lennard A, Lugtenburg PJ, Dimier N, Wassner-Fritsch E, Fingerle-Rowson G, Cheson BD. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1081-93. Epub 2016 Jun 23. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30097-3/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27345636 PubMed]
-## '''Update:''' Cheson BD, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben JG, Lennard A, Lugtenburg PJ, Fingerle-Rowson G, Mattiello F, Knapp A, Sehn LH. Overall survival benefit in patients with rituximab-refractory indolent non-Hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study. J Clin Oncol. 2018 Aug 1;36(22):2259-2266. Epub 2018 Mar 27. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.3656 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29584548 PubMed]
+##'''Update:''' Cheson BD, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben JG, Lennard A, Lugtenburg PJ, Fingerle-Rowson G, Mattiello F, Knapp A, Sehn LH. Overall survival benefit in patients with rituximab-refractory indolent non-Hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study. J Clin Oncol. 2018 Aug 1;36(22):2259-2266. Epub 2018 Mar 27. [https://ascopubs.org/doi/full/10.1200/JCO.2017.76.3656 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29584548 PubMed]
 ==Rituximab monotherapy, extended course {{#subobject:fc9136|Regimen=1}}==
@@ Line 3,929: / Line 4,296: @@
 ===Variant #1, 3-month cycles {{#subobject:c5e67c|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
+! style="width: 25%" |Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
 |[http://www.bloodjournal.org/content/108/10/3295.long Van Oers et al. 2006 (EORTC 20981)]
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#1a9851" |Phase III (E-esc)
 |[[#Observation_4|Observation]]
-|style="background-color:#91cf60"|Seems to have superior OS
+| style="background-color:#91cf60" |Seems to have superior OS
 |-
 |}
 ====Preceding treatment====
 *[[Follicular_lymphoma_-_historical#CHOP_2|CHOP]] versus [[#R-CHOP_2|R-CHOP]]
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 3,949: / Line 4,319: @@
 ===Variant #2, 2-month cycles {{#subobject:5c392f|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[http://link.springer.com/article/10.1007/s00277-014-2103-3/fulltext.html Witzens-Harig et al. 2014 (MAXIMA)]
-|style="background-color:#91cf61"|Non-randomized
+| style="background-color:#91cf61" |Non-randomized
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ Sehn et al. 2015 (GAUSS)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
 ====Preceding treatment====
 *MAXIMA: [[#Rituximab_monotherapy_3|Rituximab monotherapy]] or rituximab and chemotherapy (Most patients, 62%, received an anthracycline-based regimen)
 *GAUSS: [[#Rituximab_monotherapy_3|Rituximab]]
 ====Chemotherapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 3,969: / Line 4,341: @@
 ===References===
-# '''EORTC 20981:''' van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van 't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27. [http://www.bloodjournal.org/content/108/10/3295.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16873669 PubMed]
-## '''Update:''' van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. Epub 2010 May 3. [http://jco.ascopubs.org/content/28/17/2853.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903319/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20439641 PubMed]
+#'''EORTC 20981:''' van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van 't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27. [http://www.bloodjournal.org/content/108/10/3295.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16873669 PubMed]
-# Witzens-Harig M, Foá R, Di Rocco A, van Hazel G, Chamone DF, Rowe JM, Arcaini L, Poddubnaya I, Ho AD, Ivanova V, Vranovsky A, Thurley D, Oertel S. Maintenance with rituximab is safe and not associated with severe or uncommon infections in patients with follicular lymphoma: results from the phase IIIb MAXIMA study. Ann Hematol. 2014 Oct;93(10):1717-24. Epub 2014 May 14. Erratum in: Ann Hematol. 2014 Oct;93(10):1807. [http://link.springer.com/article/10.1007/s00277-014-2103-3/fulltext.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24824768 PubMed]
+##'''Update:''' van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. Epub 2010 May 3. [http://jco.ascopubs.org/content/28/17/2853.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903319/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20439641 PubMed]
+#Witzens-Harig M, Foá R, Di Rocco A, van Hazel G, Chamone DF, Rowe JM, Arcaini L, Poddubnaya I, Ho AD, Ivanova V, Vranovsky A, Thurley D, Oertel S. Maintenance with rituximab is safe and not associated with severe or uncommon infections in patients with follicular lymphoma: results from the phase IIIb MAXIMA study. Ann Hematol. 2014 Oct;93(10):1717-24. Epub 2014 May 14. Erratum in: Ann Hematol. 2014 Oct;93(10):1807. [http://link.springer.com/article/10.1007/s00277-014-2103-3/fulltext.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24824768 PubMed]
 <!-- Presented in part at the American Society of Hematology 53rd Annual Meeting, San Diego, CA, December 10-13, 2011. -->
-# '''GAUSS:''' Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: final analysis of the GAUSS study. J Clin Oncol. 2015 Oct 20;33(30):3467-74. Epub 2015 Aug 17. [http://jco.ascopubs.org/content/33/30/3467.full link to original article]] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26282650 PubMed]
+#'''GAUSS:''' Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: final analysis of the GAUSS study. J Clin Oncol. 2015 Oct 20;33(30):3467-74. Epub 2015 Aug 17. [http://jco.ascopubs.org/content/33/30/3467.full link to original article]] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26282650 PubMed]
 ==VR {{#subobject:70e1ea|Regimen=1}}==
@@ Line 3,984: / Line 4,357: @@
 ===Regimen {{#subobject:d6310e|Variant=1}}===
 {| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 25%" |Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116936/ Baiocchi et al. 2011 (OSU-0430)]
-|style="background-color:#ffffbe"|Phase II, <20 patients reported
+| style="background-color:#ffffbe" |Phase II, <20 patients reported
 |-
 |}
 ====Preceding treatment====
 *[[#VR|VR re-induction]]
 ====Chemotherapy====
 *[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1 & 8
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1 & 8
@@ Line 4,000: / Line 4,376: @@
 ===References===
-# '''OSU-0430:''' Baiocchi RA, Alinari L, Lustberg ME, Lin TS, Porcu P, Li X, Johnston JS, Byrd JC, Blum KA. Phase 2 trial of rituximab and bortezomib in patients with relapsed or refractory mantle cell and follicular lymphoma. Cancer. 2011 Jun 1;117(11):2442-51. Epub 2010 Dec 14. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.25792/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116936/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24048792 PubMed]
+#'''OSU-0430:''' Baiocchi RA, Alinari L, Lustberg ME, Lin TS, Porcu P, Li X, Johnston JS, Byrd JC, Blum KA. Phase 2 trial of rituximab and bortezomib in patients with relapsed or refractory mantle cell and follicular lymphoma. Cancer. 2011 Jun 1;117(11):2442-51. Epub 2010 Dec 14. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.25792/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116936/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24048792 PubMed]
 =Prognosis=
@@ Line 4,010: / Line 4,387: @@
 Each category is assigned 0 or 1 points:
 *Age
 **Less than 60 years (0 points)
@@ Line 4,027: / Line 4,405: @@
 Risk stratification:
 *'''0 or 1 points''': Low risk
 *'''2 points''': Intermediate risk
@@ Line 4,032: / Line 4,411: @@
 ===References===
-# Solal-Céligny P, Roy P, Colombat P, White J, Armitage JO, Arranz-Saez R, Au WY, Bellei M, Brice P, Caballero D, Coiffier B, Conde-Garcia E, Doyen C, Federico M, Fisher RI, Garcia-Conde JF, Guglielmi C, Hagenbeek A, Haïoun C, LeBlanc M, Lister AT, Lopez-Guillermo A, McLaughlin P, Milpied N, Morel P, Mounier N, Proctor SJ, Rohatiner A, Smith P, Soubeyran P, Tilly H, Vitolo U, Zinzani PL, Zucca E, Montserrat E. Follicular lymphoma international prognostic index. Blood. 2004 Sep 1;104(5):1258-65. Epub 2004 May 4. [http://www.bloodjournal.org/content/104/5/1258.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15126323 PubMed]
+#Solal-Céligny P, Roy P, Colombat P, White J, Armitage JO, Arranz-Saez R, Au WY, Bellei M, Brice P, Caballero D, Coiffier B, Conde-Garcia E, Doyen C, Federico M, Fisher RI, Garcia-Conde JF, Guglielmi C, Hagenbeek A, Haïoun C, LeBlanc M, Lister AT, Lopez-Guillermo A, McLaughlin P, Milpied N, Morel P, Mounier N, Proctor SJ, Rohatiner A, Smith P, Soubeyran P, Tilly H, Vitolo U, Zinzani PL, Zucca E, Montserrat E. Follicular lymphoma international prognostic index. Blood. 2004 Sep 1;104(5):1258-65. Epub 2004 May 4. [http://www.bloodjournal.org/content/104/5/1258.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15126323 PubMed]
 ==Follicular lymphoma international prognostic index (FLIPI - 2)==
@@ Line 4,041: / Line 4,421: @@
 Each category is assigned 0 or 1 points:
 *Age
 **Less than 60 years (0 points)
@@ Line 4,058: / Line 4,439: @@
 Risk stratification:
 *'''0 points''': Low risk
 *'''1 or 2 points''': Intermediate risk
@@ Line 4,063: / Line 4,445: @@
 ===References===
-# Federico M, Bellei M, Marcheselli L, Luminari S, Lopez-Guillermo A, Vitolo U, Pro B, Pileri S, Pulsoni A, Soubeyran P, Cortelazzo S, Martinelli G, Martelli M, Rigacci L, Arcaini L, Di Raimondo F, Merli F, Sabattini E, McLaughlin P, Solal-Céligny P. Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. J Clin Oncol. 2009 Sep 20;27(27):4555-62. Epub 2009 Aug 3. [http://jco.ascopubs.org/content/27/27/4555.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19652063 PubMed]
+#Federico M, Bellei M, Marcheselli L, Luminari S, Lopez-Guillermo A, Vitolo U, Pro B, Pileri S, Pulsoni A, Soubeyran P, Cortelazzo S, Martinelli G, Martelli M, Rigacci L, Arcaini L, Di Raimondo F, Merli F, Sabattini E, McLaughlin P, Solal-Céligny P. Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. J Clin Oncol. 2009 Sep 20;27(27):4555-62. Epub 2009 Aug 3. [http://jco.ascopubs.org/content/27/27/4555.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19652063 PubMed]
 =Response criteria=
 ==NCI Sponsored International Working Group Criteria (1999)==
-# Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351. [http://jco.ascopubs.org/content/17/4/1244.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10561185 PubMed]
+#Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351. [http://jco.ascopubs.org/content/17/4/1244.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10561185 PubMed]
 =Investigational agents=

Difference between revisions of "Follicular lymphoma"

Revision as of 01:10, 22 January 2020

Guidelines

ESMO

Current

Older

NCCN

Early disease, definitive therapy

Ibritumomab tiuxetan monotherapy

Regimen

Radioimmunotherapy

References

Radiation therapy

Regimen

Radiotherapy

Subsequent treatment

References

Early disease, adjuvant therapy

Observation

Regimen

Preceding treatment

References

Advanced disease, pre-phase

Rituximab monotherapy

Regimen

Chemotherapy

Subsequent treatment

References

Advanced disease, first-line therapy, randomized data

Bendamustine & Obinutuzumab

Regimen

Chemotherapy

Subsequent treatment

References

BR

Variant #1, 6 cycles

Chemotherapy

Supportive medications

Subsequent treatment

Variant #2, 6 cycles with rituximab extension

Chemotherapy

Subsequent treatment

Variant #3, 8 cycles

Chemotherapy

Supportive medications

References

Chlorambucil monotherapy

Regimen

Chemotherapy

References

Cyclophosphamide monotherapy

Regimen

Chemotherapy

References

G-CVP

Regimen

Chemotherapy

Subsequent treatment

References

G-CHOP

Regimen

Chemotherapy

Subsequent treatment

References

Lenalidomide & Rituximab

Variant #1

Chemotherapy

Variant #2

Chemotherapy

Variant #3

Chemotherapy

Variant #4

Chemotherapy

Subsequent treatment

References

Observation

Regimen

References

R-CHOP

Variant #1, 3 cycles with prednisone 100 mg

Variant #2, 3 cycles with prednisone 100 mg/m²

Variant #4, prednisone 100 mg/m²

Variant #1, prednisone 40 mg/m²