Anaplastic large cell lymphoma

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 Bhagirathbhai Dholaria, MBBS
Vanderbilt University
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Note: these studies were specific to ALCL or had ALCL subgroups; regimens used in PTCL, NOS are also often used in this condition. Certain regimens have been moved to dedicated pages:

9 regimens on this page
12 variants on this page


Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

ESMO

NCCN

Untreated

BV-CHP

BV-CHP: Brentuximab Vedotin, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Prednisone

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence Comparator Comparative Efficacy
Horwitz et al. 2018 (ECHELON-2) 2013-2016 Phase 3 (E-RT-switch-ooc) CHOP Superior PFS (primary endpoint)
Median PFS: 48.2 vs 20.8 mo
(HR 0.71, 95% CI 0.54-0.93)

Superior OS (secondary endpoint)
Median OS: NYR vs NYR
(HR 0.66, 95% CI 0.46-0.95)

Antibody-drug conjugate therapy

Chemotherapy

Glucocorticoid therapy

21-day cycle for 6 to 8 cycles

References

  1. ECHELON-2: Horwitz S, O'Connor OA, Pro B, Illidge T, Fanale M, Advani R, Bartlett NL, Christensen JH, Morschhauser F, Domingo-Domenech E, Rossi G, Kim WS, Feldman T, Lennard A, Belada D, Illés Á, Tobinai K, Tsukasaki K, Yeh SP, Shustov A, Hüttmann A, Savage KJ, Yuen S, Iyer S, Zinzani PL, Hua Z, Little M, Rao S, Woolery J, Manley T, Trümper L; ECHELON-2 Study Group. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019 Jan 19;393(10168):229-240. Epub 2018 Dec 4. Erratum in: Lancet. 2019 Jan 19;393(10168):228. link to original article contains dosing details in abstract link to PMC article PubMed NCT01777152

CHOEP-14

CHOEP-14: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Etoposide, Prednisone every 14 days
CHOPE
VACOP

Example orders

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Pfreundschuh et al. 2004 (NHL-B1) 1993-2000 Phase 3, fewer than 20 pts in this subgroup (E-esc) 1. CHOEP-21
2. CHOP-21
3. CHOP-14 		Not reported by subgroup Not reported by subgroup

Note: This regimen was used in 16 patients with ALCL in the NHL-B1 trial. The authors did not report a subgroup analysis for this minority population.

Chemotherapy

Glucocorticoid therapy

Supportive therapy

  • Filgrastim (Neupogen) by the following weight-based criteria:
    • Less than 75 kg: 300 mcg SC once per day on days 4 to 13
    • 75 kg or more: 480 mcg SC once per day on days 4 to 13

14-day cycle for 6 cycles; next cycle to start as long as WBC count is greater than 2.5 x 109/L and platelets greater than 80 x 109/L

Subsequent treatment

  • NHL-B1, patients with initial bulky disease (mass conglomerate at least 7.5 cm): RT consolidation x 3600 cGy to extranodal sites of disease when possible

References

  1. NHL-B1: Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. link to original article contains dosing details in manuscript PubMed

CHOEP-21

CHOEP-21: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Etoposide, Prednisone every 21 days
CHOPE
VACOP

Example orders

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Pfreundschuh et al. 2004 (NHL-B1) 1993-2000 Phase 3, fewer than 20 pts in this subgroup (E-esc) 1. CHOEP-14
2. CHOP-21
3. CHOP-14 		Not reported by subgroup Not reported by subgroup

Note: This regimen was used in 20 patients with ALCL in the NHL-B1 trial. The authors did not report a subgroup analysis for this minority population.

Chemotherapy

Glucocorticoid therapy

Supportive therapy

21-day cycle for 6 cycles; next cycle to start as long as WBC count is greater than 2.5 x 109/L and platelets greater than 80 x 109/L

Subsequent treatment

  • NHL-B1, patients with initial bulky disease (mass conglomerate at least 7.5 cm): RT consolidation x 3600 cGy to extranodal sites of disease when possible

References

  1. NHL-B1: Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. link to original article contains dosing details in manuscript PubMed

CHOP

CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
CHOP-21
ACOP
CAVP
COPA
VACP
VCAP

Regimen variant #1, capped vincristine

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Horwitz et al. 2018 (ECHELON-2) 2013-2016 Phase 3 (C) BV-CHP Inferior OS

Chemotherapy

Glucocorticoid therapy

21-day cycle for 6 to 8 cycles


Regimen variant #2, flat-dose vincristine

Study Dates of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Pfreundschuh et al. 2004 (NHL-B1) 1993-2000 Phase 3, fewer than 20 pts in this subgroup (C) 1. CHOEP-14
2. CHOEP-21
3. CHOP-14 		Not reported by subgroup Not reported by subgroup

Note: This regimen was used in 14 patients with ALCL in NHL-B1. The authors did not report a subgroup analysis for this minority population.

Chemotherapy

Glucocorticoid therapy

Supportive therapy

  • At the discretion of ordering physician: Filgrastim (Neupogen) by the following weight-based criteria:
    • Less than 75 kg: 300 mcg SC once per day on days 4 to 13
    • 75 kg or more: 480 mcg SC once per day on days 4 to 13

21-day cycle for 6 cycles

References

  1. NHL-B1: Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. link to original article contains dosing details in manuscript PubMed
  2. ECHELON-2: Horwitz S, O'Connor OA, Pro B, Illidge T, Fanale M, Advani R, Bartlett NL, Christensen JH, Morschhauser F, Domingo-Domenech E, Rossi G, Kim WS, Feldman T, Lennard A, Belada D, Illés Á, Tobinai K, Tsukasaki K, Yeh SP, Shustov A, Hüttmann A, Savage KJ, Yuen S, Iyer S, Zinzani PL, Hua Z, Little M, Rao S, Woolery J, Manley T, Trümper L; ECHELON-2 Study Group. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019 Jan 19;393(10168):229-240. Epub 2018 Dec 4. Erratum in: Lancet. 2019 Jan 19;393(10168):228. link to original article contains dosing details in abstract link to PMC article PubMed NCT01777152

DA-EPOCH

DA-EPOCH: Dose Adjusted Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)

Regimen

Study Dates of enrollment Evidence
Dunleavy et al. 2015 (NCI 93-C-0133ALCL) 1993-2009 Phase 2

Note: this should be considered a substudy under the master protocol NCI 93-C-0133.

Chemotherapy

Glucocorticoid therapy

Supportive therapy

21-day cycle for 6 to 8 cycles

Dose and schedule modifications

  • Start cycle 1 as described above.
  • Obtain CBCs twice per week for nadir measurements.
  • If nadir ANC greater than 500/μL, increase etoposide, doxorubicin, and cyclophosphamide by one level (20%) compared to previous cycle.
  • If nadir ANC less than 500/μL, use same doses as last cycle.
  • If nadir platelet count less than 25 x 109/L, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to the previous cycle.

References

  1. NCI 93-C-0133ALCL: Dunleavy K, Pittaluga S, Shovlin M, Roschewski M, Lai C, Steinberg SM, Jaffe ES, Wilson WH. Phase II trial of dose-adjusted EPOCH in untreated systemic anaplastic large cell lymphoma. Haematologica. 2016 Jan;101(1):e27-9. Epub 2015 Oct 30. link to original article refers to protocol in Dunleavy et al. 2013 link to PMC article PubMed NCT00001337

Relapsed or refractory, salvage therapy

Brentuximab vedotin monotherapy

Regimen variant #1, 16 cycles

Study Dates of enrollment Evidence
Pro et al. 2012 (SG035-0004) 2009-2010 Phase 2 (RT)

Antibody-drug conjugate therapy

21-day cycle for up to 16 infusions


Regimen variant #2, bridge to transplant

Study Evidence
Gibb et al. 2012 Named Patient Programme

Antibody-drug conjugate therapy

21-day cycles until transplant


Regimen variant #3, indefinite

Study Dates of enrollment Evidence
Gopal et al. 2012 (SGN35-006) 2009-NR Phase 2, fewer than 20 pts in subgroup

Note: SGN35-006 is a re-treatment trial; all patients were previously exposed to brentuximab vedotin. Patients who had received the 1.2 mg/kg dose on a prior trial also received that dose at re-treatment.

Antibody-drug conjugate therapy

21-day cycles

References

  1. SGN35-006: Gopal AK, Ramchandren R, O'Connor OA, Berryman RB, Advani RH, Chen R, Smith SE, Cooper M, Rothe A, Matous JV, Grove LE, Zain J. Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation. Blood. 2012 Jul 19;120(3):560-8. Epub 2012 Apr 17. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00947856
    1. Update: Bartlett NL, Chen R, Fanale MA, Brice P, Gopal A, Smith SE, Advani R, Matous JV, Ramchandren R, Rosenblatt JD, Huebner D, Levine P, Grove L, Forero-Torres A. Retreatment with brentuximab vedotin in patients with CD30-positive hematologic malignancies. J Hematol Oncol. 2014 Mar 19;7:24. link to original article contains dosing details in manuscript link to PMC article PubMed
  2. SG035-0004: Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, Matous J, Ramchandren R, Fanale M, Connors JM, Yang Y, Sievers EL, Kennedy DA, Shustov A. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol. 2012 Jun 20;30(18):2190-6. Epub 2012 May 21. link to original article contains dosing details in manuscript PubMed NCT00866047
    1. Update: Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, Matous J, Ramchandren R, Fanale M, Connors JM, Fenton K, Huebner D, Pinelli JM, Kennedy DA, Shustov A. Five-year results of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma. Blood. 2017 Dec 21;130(25):2709-2717. Epub 2017 Oct 3. link to original article link to PMC article PubMed
  3. Gibb A, Jones C, Bloor A, Kulkarni S, Illidge T, Linton K, Radford J. Brentuximab vedotin in refractory CD30+ lymphomas: a bridge to allogeneic transplantation in approximately one quarter of patients treated on a Named Patient Programme at a single UK center. Haematologica. 2013 Apr;98(4):611-4. Epub 2012 Oct 12. link to original article contains dosing details in manuscript link to PMC article PubMed
  4. Retrospective: Gopal AK, Bartlett NL, Forero-Torres A, Younes A, Chen R, Friedberg JW, Matous JV, Shustov AR, Smith SE, Zain J, O'Meara MM, Fanale MA. Brentuximab vedotin in patients aged 60 years or older with relapsed or refractory CD30-positive lymphomas: a retrospective evaluation of safety and efficacy. Leuk Lymphoma. 2014 Oct;55(10):2328-34. Epub 2014 Feb 24. link to original article PubMed

DHAP

DHAP: Dexamethasone, High-dose Ara-C (cytarabine), Platinol (cisplatin)

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Crump et al. 2014 (NCIC-CTG LY.12) 2003-2011 Phase 3, <20 in this arm (C) GDP Non-inferior ORR

Chemotherapy

  • Cytarabine (Ara-C) 2000 mg/m2 IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m2)
  • Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours, started on day 1

Glucocorticoid therapy

21-day cycle for up to 3 cycles

References

  1. NCIC-CTG LY.12: Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains dosing details in manuscript PubMed NCT00078949

GDP

GDP: Gemcitabine, Dexamethasone, Platinol (Cisplatin)

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Crump et al. 2014 (NCIC-CTG LY.12) 2003-2011 Phase 3, fewer than 20 pts in this arm (E-switch-ic) DHAP Non-inferior ORR (co-primary endpoint)

Chemotherapy

Glucocorticoid therapy

21-day cycle for up to 3 cycles

References

  1. NCIC-CTG LY.12: Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains dosing details in manuscript PubMed NCT00078949

Consolidation after salvage therapy

Fludarabine, Busulfan, Cyclophosphamide, then allo HSCT

FluBuCy: Fludarabine, Busulfan, Cyclophosphamide

Regimen variant #1, oral

Study Dates of enrollment Evidence
Glass et al. 2014 (DSHNHL R3) 2004-06-16 to 2009-03-24 Phase 2

Chemotherapy

Immunotherapy

GVHD prophylaxis

One course


Regimen variant #2, intravenous

Study Dates of enrollment Evidence
Glass et al. 2014 (DSHNHL R3) 2004-06-16 to 2009-03-24 Phase 2

Chemotherapy

Immunotherapy

GVHD prophylaxis

One course

References

  1. DSHNHL R3: Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. link to original article link to original protocol (in German) contains dosing details in manuscript PubMed NCT00785330
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