Page editor		Section editor
	Samuel M. Rubinstein, MD University of North Carolina Chapel Hill, NC rubinstein_md		Andrew J. Cowan, MD University of Washington Seattle, WA andrewcowanmd LinkedIn

25 regimens on this page 48 variants on this page

Guidelines

BSH

2014: Wechalekar et al. Guidelines on the management of AL amyloidosis PubMed

EMN

2018: Gavriatopoulou et al. European myeloma network recommendations on diagnosis and management of patients with rare plasma cell dyscrasias PubMed

NCCN

NCCN Guidelines - Systemic Light Chain Amyloidosis

First-line therapy (including transplant ineligible)

Colchicine monotherapy

back to top

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kyle et al. 1985	NR	Randomized (E-switch-ooc)	MP	Seems not superior
Cohen et al. 1987	1976-1983	Non-randomized
Kyle et al. 1997	1982-1992	Phase III (C)	1. MP	Inferior OS
Kyle et al. 1997	1982-1992	Phase III (C)	2. Melphalan, Prednisone, Colchicine	Inferior OS

Of historic interest.

Chemotherapy

Colchicine (Colcrys)

References

Kyle RA, Greipp PR, Garton JP, Gertz MA. Primary systemic amyloidosis: comparison of melphalan/prednisone versus colchicine. Am J Med. 1985 Dec;79(6):708-16. link to original article PubMed
Cohen AS, Rubinow A, Anderson JJ, Skinner M, Mason JH, Libbey C, Kayne H. Survival of patients with primary (AL) amyloidosis: colchicine-treated cases from 1976 to 1983 compared with cases seen in previous years (1961 to 1973). Am J Med. 1987 Jun;82(6):1182-90. link to original article PubMed
Kyle RA, Gertz MA, Greipp PR, Witzig TE, Lust JA, Lacy MQ, Therneau TM. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone, and colchicine. N Engl J Med. 1997 Apr 24;336(17):1202-7. link to original article PubMed

CRd

back to top

CRd: Cyclophosphamide, Revlimid (Lenalidomide), low-dose dexamethasone
LDC: Lenalidomide, Dexamethasone, Cyclophosphamide
RdC: Revlimid (Lenalidomide), low-dose dexamethasone, Cyclophosphamide

Regimen variant #1, "LDC"

Study	Evidence
Cibeira et al. 2015	Phase II

Chemotherapy

Cyclophosphamide (Cytoxan) as follows:
- Cycles 1 to 6: 300 mg/m² IV once per day on days 1 & 8
- Cycles 7 to 12: 300 mg/m² IV once on day 1
Lenalidomide (Revlimid) as follows:
- Normal eGFR: 15 mg PO once per day on days 1 to 21
- eGFR greater than 30 mL/min/1.73m² but less than 50 mL/min/1.73m²: 10 mg PO once per day on days 1 to 21
- eGFR less than 30 mL/min/1.73m²: 5 mg PO once per day on days 1 to 21
Dexamethasone (Decadron) as follows:
- Cycles 1 to 6: 20 mg PO once per day on days 1 to 4, 9 to 12
- Cycles 7 to 12: 20 mg PO once per day on days 1 to 4
- Cardiac stage III (this is not defined): upfront modification "allowed" but not defined

Supportive medications

Aspirin 100 mg PO once per day, or Low molecular weight heparin

28-day cycle for 12 cycles

Subsequent treatment

Patients without progression who were tolerating therapy: Rd maintenance

Regimen variant #2, "CRd"

Study	Evidence
Kumar et al. 2012	Phase II

Chemotherapy

Cyclophosphamide (Cytoxan) 500 mg PO once per day on days 1, 8, 15
Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 21
Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22

Supportive medications

Thromboprophylaxis as follows:
- Standard patients: Aspirin 81 to 325 mg PO once per day
- Patients with previous thrombotic histories or who were considered to be higher thrombotic risks: low molecular weight heparin or Warfarin (Coumadin)
"Routine antibiotic, antiviral, or antifungal prophylaxis was not mandated and left to the discretion of the treating physician."

28-day cycle for up to 26 cycles (2 years)

Regimen variant #3, "RdC"

Study	Evidence
Kastritis et al. 2012	Phase I/II

This was the highest dose level tested in Kastritis et al. 2012, which had no dose-limiting toxicities.

Chemotherapy

Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 21
Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4
Cyclophosphamide (Cytoxan) 100 mg PO once per day on days 1 to 10

Supportive medications

Thromboprophylaxis: Aspirin 100 mg PO once per day
Proton pump inhibitor
Trimethoprim-sulfamethoxazole (Bactrim), dose and schedule not listed
Valacyclovir (Valtrex), dose and schedule not listed

28-day cycle for 12 cycles

References

Kumar SK, Hayman SR, Buadi FK, Roy V, Lacy MQ, Gertz MA, Allred J, Laumann KM, Bergsagel LP, Dingli D, Mikhael JR, Reeder CB, Stewart AK, Zeldenrust SR, Greipp PR, Lust JA, Fonseca R, Russell SJ, Rajkumar SV, Dispenzieri A. Lenalidomide, cyclophosphamide, and dexamethasone (CRd) for light-chain amyloidosis: long-term results from a phase 2 trial. Blood. 2012 May 24;119(21):4860-7. Epub 2012 Apr 13. link to original article contains verified protocol link to PMC article PubMed
Kastritis E, Terpos E, Roussou M, Gavriatopoulou M, Pamboukas C, Boletis I, Marinaki S, Apostolou T, Nikitas N, Gkortzolidis G, Michalis E, Delimpasi S, Dimopoulos MA. A phase 1/2 study of lenalidomide with low-dose oral cyclophosphamide and low-dose dexamethasone (RdC) in AL amyloidosis. Blood. 2012 Jun 7;119(23):5384-90. Epub 2012 Apr 18. link to original article contains verified protocol PubMed
Cibeira MT, Oriol A, Lahuerta JJ, Mateos MV, de la Rubia J, Hernández MT, Granell M, Fernández de Larrea C, San Miguel JF, Bladé J; PETHEMA. A phase II trial of lenalidomide, dexamethasone and cyclophosphamide for newly diagnosed patients with systemic immunoglobulin light chain amyloidosis. Br J Haematol. 2015 Sep;170(6):804-13. Epub 2015 May 14. link to original article contains verified protocol PubMed

CTD

back to top

CTD: Cyclophosphamide, Thalidomide, Dexamethasone

Regimen variant #1

Study	Evidence
Wechalekar et al. 2007	Phase II

Chemotherapy

Cyclophosphamide (Cytoxan) 500 mg PO once per day on days 1, 8, 15
Thalidomide (Thalomid) 100 mg PO once per day on days 1 to 21, then increased to 200 mg PO once per day if well tolerated after 4 weeks
Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 9 to 12

Supportive medications

"Antimicrobial and thromboprophylaxis were given according to local protocol"; no routine thromboprophylaxis

21-day cycles, "given until a stable clonal response was achieved on consecutive samples at least 4 weeks apart" or until confirmed lack of response

Regimen variant #2, risk attenuated regimen

Study	Evidence
Wechalekar et al. 2007	Phase II

For elderly patients (age greater than 70 years), NYHA heart failure greater than class II, and those with significant fluid overload.

Chemotherapy

Cyclophosphamide (Cytoxan) 500 mg PO once per day on days 1, 8, 15
Thalidomide (Thalomid) as follows:
- Cycle 1: 50 mg PO once per day
- Cycle 2 (if tolerated): 100 mg PO once per day
- Cycle 3 (if tolerated): 150 mg PO once per day
- Cycle 4 onwards (if tolerated): 200 mg PO once per day
Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4, 15 to 18

Supportive medications

"Antimicrobial and thromboprophylaxis were given according to local protocol"; no routine thromboprophylaxis

28-day cycles, "given until a stable clonal response was achieved on consecutive samples at least 4 weeks apart" or until confirmed lack of response

References

Wechalekar AD, Goodman HJ, Lachmann HJ, Offer M, Hawkins PN, Gillmore JD. Safety and efficacy of risk-adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL amyloidosis. Blood. 2007 Jan 15;109(2):457-64. Epub 2006 Sep 21. link to original article contains verified protocol PubMed

Dara-CyBorD

back to top

Dara-CyBorD: Daratumumab and hyaluronidase, Cyclophosphamide, Bortezomib, Dexamethasone
D-VCd: Daratumumab and hyaluronidase, Velcade (Bortezomib), Cyclophosphamide, low-dose dexamethasone

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Abstract: Kastritis et al. 2020 (ANDROMEDA)	2017-2020	Phase III (E-RT-esc)	CyBorD	Superior complete hematologic response rate

Targeted therapy

Daratumumab and hyaluronidase (Darzalex Faspro) as follows:
- Cycles 1 & 2: 1800 mg SC once per day on days 1, 8, 15, 22
- Cycles 3 to 6: 1800 mg SC once per day on days 1 & 15
- Cycle 7 onwards: 1800 mg SC once on day 1

Chemotherapy

Cyclophosphamide (Cytoxan) 300 mg/m² PO once per day on days 1, 8, 15, 22
Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22

28-day cycle for 6 cycles

Subsequent treatment

Daratumumab maintenance x 2 years

References

Abstract: Kastritis E, Palladini G, Minnema MC, Wechalekar AD, Jaccard A, Lee HC, Sanchorawala V, Gibbs S, Mollee P, Venner CP, Lu J, Schonland S, Gatt ME, Suzuki K, Kim K, Cibeira MT, Beksac M, Libby E, Valent J, HJungria V, Wong SW, Rosenzweig M, Bumma N, Chauveau D, Ahmadi T, Tran N, Qin X, Vasey SY, Tromp B, Schechter JM, Weiss BM, Vermeulen J, Merlini G, Comenzo RL. Subcutaneous Daratumumab + Cyclophosphamide, Bortezomib, and Dexamethasone (CyBorD) in patients with mewly diagnosed light chain (AL) amyloidosis: primary results from the phase 3 ANDROMEDA study. 25th EHA Congress. Frankfurt. 2020. link to abstract NCT03201965

Lenalidomide monotherapy

back to top

Regimen variant #1, 15 mg dosing

Study	Evidence
Sanchorwala et al. 2006	Phase II

The trial used an initial dose of lenalidomide of 25 mg PO once per day, but it was reduced to 15 mg because 25 mg was poorly tolerated.

Chemotherapy

Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 21

Supportive medications

Aspirin 81 mg or 325 mg (physician discretion) PO once per day

28-day cycles

Subsequent treatment

If no response after 3 cycles of therapy, then patients were escalated to lenalidomide & dexamethasone. Otherwise, treatment continued indefinitely

Regimen variant #2, 25 mg dosing

Study	Evidence
Dispenzieri et al. 2006	Phase II

Chemotherapy

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

28-day cycles

Subsequent treatment

If no response after 3 cycles of therapy, then patients were escalated to lenalidomide & dexamethasone. Otherwise, treatment continued up to 12 cycles

References

Sanchorawala V, Wright DG, Rosenzweig M, Finn KT, Fennessey S, Zeldis JB, Skinner M, Seldin DC. Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial. Blood. 2007 Jan 15;109(2):492-6. Epub 2006 Sep 7. link to original article contains verified protocol PubMed
1. Update: Sanchorawala V, Finn KT, Fennessey S, Shelton A, Doros G, Zeldis JB, Seldin DC. Durable hematologic complete responses can be achieved with lenalidomide in AL amyloidosis. Blood. 2010 Sep 16;116(11):1990-1. link to original article PubMed
Dispenzieri A, Lacy MQ, Zeldenrust SR, Hayman SR, Kumar SK, Geyer SM, Lust JA, Allred JB, Witzig TE, Rajkumar SV, Greipp PR, Russell SJ, Kabat B, Gertz MA. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood. 2007 Jan 15;109(2):465-70. Epub 2006 Sep 28. link to original article contains verified protocol PubMed

M-DEX

back to top

M-DEX: Melphalan & DEXamethasone

Regimen variant #1, BSA-based melphalan

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Jaccard et al. 2007	2000-2005	Phase III (C)	High-dose melphalan, then auto HSCT	Seems to have superior OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

Chemotherapy

Melphalan (Alkeran) 10 mg/m² PO once per day on days 1 to 4
Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4

Supportive medications

Proton pump inhibitor
Trimethoprim-Sulfamethoxazole (Bactrim DS) three times per week

1-month cycle for up to 18 cycles

Patients achieving complete hematologic remission could stop treatment after 12 cycles.

Regimen variant #2, weight-based melphalan

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Palladini et al. 2003	1999-2002	Phase II
Kastritis et al. 2020 (EMN-03)	2011-2016	Phase III (C)	BMDex	Inferior OS

Chemotherapy

Melphalan (Alkeran) 0.22 mg/kg PO once per day on days 1 to 4
Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4

Supportive medications

Omeprazole (Prilosec) 20 mg PO once per day on days 1 to 10
Ciprofloxacin (Cipro) 250 mg PO twice per day on days 1 to 10
Itraconazole (Sporanox) 100 mg PO once per day on days 1 to 10

28-day cycle for up to 9 cycles

References

Palladini G, Perfetti V, Obici L, Caccialanza R, Semino A, Adami F, Cavallero G, Rustichelli R, Virga G, Merlini G. Association of melphalan and high-dose dexamethasone is effective and well tolerated in patients with AL (primary) amyloidosis who are ineligible for stem cell transplantation. Blood. 2004 Apr 15;103(8):2936-8. Epub 2003 Dec 18. link to original article contains protocol PubMed
1. Update: Palladini G, Russo P, Nuvolone M, Lavatelli F, Perfetti V, Obici L, Merlini G. Treatment with oral melphalan plus dexamethasone produces long-term remissions in AL amyloidosis. Blood. 2007 Jul 15;110(2):787-8. link to original article PubMed
2. Update: Palladini G, Milani P, Foli A, Obici L, Lavatelli F, Nuvolone M, Caccialanza R, Perlini S, Merlini G. Oral melphalan and dexamethasone grants extended survival with minimal toxicity in AL amyloidosis: long-term results of a risk-adapted approach. Haematologica. 2014 Apr;99(4):743-50. Epub 2013 Nov 8. link to original article link to PMC article PubMed
Jaccard A, Moreau P, Leblond V, Leleu X, Benboubker L, Hermine O, Recher C, Asli B, Lioure B, Royer B, Jardin F, Bridoux F, Grosbois B, Jaubert J, Piette JC, Ronco P, Quet F, Cogne M, Fermand JP; MAG; IFM. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med. 2007 Sep 13;357(11):1083-93. link to original article contains verified protocol PubMed NCT00344526
EMN-03: Kastritis E, Leleu X, Arnulf B, Zamagni E, Cibeira MT, Kwok F, Mollee P, Hájek R, Moreau P, Jaccard A, Schönland SO, Filshie R, Nicolas-Virelizier E, Augustson B, Mateos MV, Wechalekar A, Hachulla E, Milani P, Dimopoulos MA, Fermand JP, Foli A, Gavriatopoulou M, Klersy C, Palumbo A, Sonneveld P, Johnsen HE, Merlini G, Palladini G. Bortezomib, Melphalan, and Dexamethasone for Light-Chain Amyloidosis. J Clin Oncol. 2020 Oct 1;38(28):3252-3260. Epub 2020 Jul 30. link to original article contains verified protocol PubMed NCT01277016

MP

back to top

MP: Melphalan & Prednisone

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kyle et al. 1978	NR	Randomized (E-esc)	Placebo	Longer time on treatment
Kyle et al. 1985	NR	Randomized (E-switch-ooc)	Colchicine	Seems not superior
Kyle et al. 1997	1982-1992	Phase III (C)	1. Colchicine	Superior OS
Kyle et al. 1997	1982-1992	Phase III (C)	2. Melphalan, Prednisone, Colchicine	Seems not superior

Of historic interest.

Chemotherapy

References

Kyle RA, Greipp PR. Primary systemic amyloidosis: comparison of melphalan and prednisone versus placebo. Blood. 1978 Oct;52(4):818-27. link to original article PubMed
Kyle RA, Greipp PR, Garton JP, Gertz MA. Primary systemic amyloidosis: comparison of melphalan/prednisone versus colchicine. Am J Med. 1985 Dec;79(6):708-16. link to original article PubMed
Kyle RA, Gertz MA, Greipp PR, Witzig TE, Lust JA, Lacy MQ, Therneau TM. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone, and colchicine. N Engl J Med. 1997 Apr 24;336(17):1202-7. link to original article PubMed

MRD

back to top

MRD: Melphalan, Revlimid (Lenalidomide), Dexamethasone
L-M-Dex: Lenalidomide, Melphalan, Dexamethasone

Regimen variant #1, "L-M-Dex"

Study	Evidence
Hegenbart et al. 2017	Phase II

Note: the manuscript states "treatment consisted of a total of 6 times 4 cycles"; this has been clarified with the authors to mean 6 times 4-week cycles.

Chemotherapy

Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
Melphalan (Alkeran) 0.15 mg/kg PO once per day on days 1 to 4
Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4

28-day cycle for 6 cycles

Supportive medications

Thromboprophylaxis with ONE of the following:
- Standard patients: Aspirin 100 mg PO once per day
- Patients with a history of VTE or thrombophilia: low-molecular weight heparin (dose/schedule not specified)

Regimen variant #2

Study	Evidence
Sanchorwala et al. 2012	Phase II, <20 pts

Sanchorawala et al. 2012 did not outright specify oral routes for melphalan and dexamethasone, but this is assumed based on how the paper discussed existing oral melphalan and dexamethasone regimens.

Chemotherapy

Melphalan (Alkeran) 5 mg/m² PO once per day on days 1 to 4
Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22

Supportive medications

Aspirin 325 mg PO once per day to decrease risk of Lenalidomide (Revlimid)-associated venous thromboembolism (VTE)
Proton pump inhibitor to decrease risk of gastritis from Dexamethasone (Decadron)

28-day cycle for 12 cycles

Regimen variant #3

Study	Evidence
Moreau et al. 2010	Phase I/II

This is the MTD dosing.

Chemotherapy

Melphalan (Alkeran) 0.18 mg/kg PO once per day on days 1 to 4
Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 21
Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4

Supportive medications

LMWH for the first 4 cycles, then Aspirin as another option if no thrombosis

28-day cycle for up to 9 cycles

References

Moreau P, Jaccard A, Benboubker L, Royer B, Leleu X, Bridoux F, Salles G, Leblond V, Roussel M, Alakl M, Hermine O, Planche L, Harousseau JL, Fermand JP. Lenalidomide in combination with melphalan and dexamethasone in patients with newly diagnosed AL amyloidosis: a multicenter phase 1/2 dose-escalation study. Blood. 2010 Dec 2;116(23):4777-82. Epub 2010 Aug 19. link to original article contains verified protocol PubMed
Sanchorawala V, Patel JM, Sloan JM, Shelton AC, Zeldis JB, Seldin DC. Melphalan, lenalidomide and dexamethasone for the treatment of immunoglobulin light chain amyloidosis: results of a phase II trial. Haematologica. 2013 May;98(5):789-92. Epub 2012 Nov 9. link to original article contains verified protocol link to PMC article PubMed
Hegenbart U, Bochtler T, Benner A, Becker N, Kimmich C, Kristen AV, Beimler J, Hund E, Zorn M, Freiberger A, Gawlik M, Goldschmidt H, Hose D, Jauch A, Ho AD, Schönland SO. Lenalidomide/melphalan/dexamethasone in newly diagnosed patients with immunoglobulin light chain amyloidosis: results of a prospective phase 2 study with long-term follow up. Haematologica. 2017 Aug;102(8):1424-1431. Epub 2017 May 18. link to original article contains verified protocolPubMed

No induction

back to top

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Huang et al. 2014 (NJCT-0703)	2009-2012	Randomized Phase II (C)	BD	Seems to have inferior OS

No induction prior to transplant.

Subsequent treatment

High-dose melphalan with autologous hematopoietic stem cell transplant

References

NJCT-0703: Huang X, Wang Q, Chen W, Zeng C, Chen Z, Gong D, Zhang H, Liu Z. Induction therapy with bortezomib and dexamethasone followed by autologous stem cell transplantation versus autologous stem cell transplantation alone in the treatment of renal AL amyloidosis: a randomized controlled trial. BMC Med. 2014 Jan 6;12:2. link to original article contains verified protocol link to PMC article PubMed NCT01998503

VD

back to top

VD: Velcade (Bortezomib) & Dexamethasone

Regimen variant #1, lower-dose dex

Study	Evidence	Efficacy
Sanchorawala et al. 2015 (X05292)	Phase II	HRR: 77%
Minnema et al. 2019 (HOVON 104)	Phase II	HRR: 80%

Chemotherapy

Bortezomib (Velcade) 1.3 mg/m² IV once per day on days 1, 4, 8, 11
Dexamethasone (Decadron) 20 mg PO once per day on days 1, 4, 8, 11

Supportive medications

21-day cycle for 2 cycles

Subsequent treatment

Bortezomib & high-dose melphalan with autologous hematopoietic stem cell transplant

Regimen variant #2, higher-dose dex

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Huang et al. 2014 (NJCT-0703)	2009-2012	Randomized Phase II (E-esc)	No induction	Seems to have superior OS

Chemotherapy

Bortezomib (Velcade) 1.3 mg/m² IV once per day on days 1, 4, 8, 11
Dexamethasone (Decadron) 40 mg PO once per day on days 1, 4, 8, 11

21-day cycle for 2 cycles

Subsequent treatment

High-dose melphalan with autologous hematopoietic stem cell transplant

References

NJCT-0703: Huang X, Wang Q, Chen W, Zeng C, Chen Z, Gong D, Zhang H, Liu Z. Induction therapy with bortezomib and dexamethasone followed by autologous stem cell transplantation versus autologous stem cell transplantation alone in the treatment of renal AL amyloidosis: a randomized controlled trial. BMC Med. 2014 Jan 6;12:2. link to original article contains verified protocol link to PMC article PubMed NCT01998503
X05292: Sanchorawala V, Brauneis D, Shelton AC, Lo S, Sun F, Sloan JM, Quillen K, Seldin DC. Induction therapy with bortezomib followed by bortezomib-high dose melphalan and stem cell transplantation for light chain amyloidosis: Results of a prospective clinical trial. Biol Blood Marrow Transplant. 2015 Aug;21(8):1445-51. Epub 2015 Apr 6. link to original article contains verified protocol PubMed
HOVON 104: Minnema MC, Nasserinejad K, Hazenberg B, Hegenbart U, Vlummens P, Ypma PF, Kröger N, Wu KL, Kersten MJ, Schaafsma MR, Croockewit S, de Waal E, Zweegman S, Tick L, Broijl A, Koene H, Bos G, Sonneveld P, Schönland S. Bortezomib-based induction followed by stem cell transplantation in light chain amyloidosis: results of the multicenter HOVON 104 trial. Haematologica. 2019 Nov;104(11):2274-2282. link to original article contains verified protocol PubMed

VDC

back to top

VDC: Velcade (Bortezomib), Dexamethasone, Cyclophosphamide
CyBorD: Cyclophosphamide, Bortezomib, Dexamethasone

Regimen variant #1, 300/1.3/40

Study	Evidence
Mikhael et al. 2012	Retrospective

Note: Mikhael et al. 2012 does not explicitly define the route for bortezomib or dexamethasone; the routes below were used in the majority of patients, per the authors.

Chemotherapy

Cyclophosphamide (Cytoxan) 300 mg/m² PO once per day on days 1, 8, 15, 22
Bortezomib (Velcade) 1.3 mg/m² SC once per day on days 1, 4, 8, 11
Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22

Supportive medications

Antiviral prophylaxis

28-day cycle for 2 to 6 cycles

Regimen variant #2, 300/1.5/40

Study	Evidence
Mikhael et al. 2012	Retrospective

Note: Mikhael et al. 2012 does not explicitly define the route for bortezomib or dexamethasone; the routes below were used in the majority of patients, per the authors.

Chemotherapy

Cyclophosphamide (Cytoxan) 300 mg/m² PO once per day on days 1, 8, 15, 22
Bortezomib (Velcade) 1.5 mg/m² SC once per day on days 1, 8, 15, 22
Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22

Supportive medications

Antiviral prophylaxis

28-day cycle for 2 to 6 cycles

References

Retrospective: Mikhael JR, Schuster SR, Jimenez-Zepeda VH, Bello N, Spong J, Reeder CB, Stewart AK, Bergsagel PL, Fonseca R. Cyclophosphamide-bortezomib-dexamethasone (CyBorD) produces rapid and complete hematologic response in patients with AL amyloidosis. Blood. 2012 May 10;119(19):4391-4. Epub 2012 Feb 13. link to original article contains verified protocol link to PMC article PubMed
Retrospective: Jaccard A, Comenzo RL, Hari P, Hawkins PN, Roussel M, Morel P, Macro M, Pellegrin JL, Lazaro E, Mohty D, Mercie P, Decaux O, Gillmore J, Lavergne D, Bridoux F, Wechalekar AD, Venner CP. Efficacy of bortezomib, cyclophosphamide and dexamethasone in treatment-naïve patients with high-risk cardiac AL amyloidosis (Mayo Clinic stage III). Haematologica. 2014 Sep;99(9):1479-85. Epub 2014 May 23. link to original article link to PMC article PubMed
Retrospective: Palladini G, Sachchithanantham S, Milani P, Gillmore J, Foli A, Lachmann H, Basset M, Hawkins P, Merlini G, Wechalekar AD. A European collaborative study of cyclophosphamide, bortezomib, and dexamethasone in upfront treatment of systemic AL amyloidosis. Blood. 2015 Jul 30;126(5):612-5. Epub 2015 May 18. link to original article PubMed

VMD

back to top

VMD: Velcade (Bortezomib), Melphalan, Dexamethasone
BMDex: Bortezomib, Melphalan, Dexamethasone

Regimen variant #1, 8 cycles

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kastritis et al. 2020 (EMN-03)	2011-2016	Phase III (E-esc)	MDex	Superior OS

Note: bortezomib administration was switched from IV to SC after the first 10 patients were enrolled in this arm.

Chemotherapy

Bortezomib (Velcade) as follows:
- Cycles 1 & 2: 1.3 mg/m² SC once per day on days 1, 4, 8, 11
- Cycles 3 to 8: 1.3 mg/m² SC once per day on days 1, 8, 15, 22
Melphalan (Alkeran) 0.22 mg/kg PO once per day on days 1 to 4
Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4

28-day cycle for 2 cycles, then 35-day cycle for 6 cycles

Regimen variant #2, 20 cycles

Study	Evidence
Zonder et al. 2009	Phase II

Chemotherapy

Bortezomib (Velcade) as follows, given first:
- No peripheral neuropathy at baseline: 1.3 mg/m² IV once per day on days 1, 8, 15, 22
- Peripheral neuropathy at baseline: 1 mg/m² IV once per day on days 1, 8, 15, 22
Melphalan (Alkeran) as follows, given third
- Serum creatinine up to 2.5 mg/dL: 9 mg/m² PO once per day on days 1 to 4
- Serum creatinine greater than 2.5 mg/dL: 6 mg/m² PO once per day on days 1 to 4
Dexamethasone (Decadron) as follows, given second
- Patients up to 70 years old: 40 mg IV or PO once per day on days 1, 8, 15, 22
- Patients older than 70, with peripheral edema, or congestive heart failure (CHF): 20 mg IV or PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23

4- to 6-week cycle for up to 20 cycles

References

Abstract: Zonder JA, Sanchorawala V, Snyder RM, Matous J, Terebelo H, Janakiraman N, Mapara MY, Lalo S, Tageja N, Webb C, Monsma D, Sellers C, Abrams J, Gasparetto C. Melphalan and Dexamethasone Plus Bortezomib Induces Hematologic and Organ Responses in AL Amyloidosis with Tolerable Neurotoxicity. Blood (ASH Annual Meeting Abstracts), Nov 2009; 114: 746. link to abstract
EMN-03: Kastritis E, Leleu X, Arnulf B, Zamagni E, Cibeira MT, Kwok F, Mollee P, Hájek R, Moreau P, Jaccard A, Schönland SO, Filshie R, Nicolas-Virelizier E, Augustson B, Mateos MV, Wechalekar A, Hachulla E, Milani P, Dimopoulos MA, Fermand JP, Foli A, Gavriatopoulou M, Klersy C, Palumbo A, Sonneveld P, Johnsen HE, Merlini G, Palladini G. Bortezomib, Melphalan, and Dexamethasone for Light-Chain Amyloidosis. J Clin Oncol. 2020 Oct 1;38(28):3252-3260. Epub 2020 Jul 30. link to original article contains verified protocol PubMed NCT01277016

Consolidation after first-line therapy

Bortezomib & Melphalan, then auto HSCT

back to top

Regimen variant #1, HDM 140 mg/m²

Study	Evidence	Efficacy
Sanchorawala et al. 2015 (X05292)	Phase II	HRR: 77%

Preceding treatment

Bortezomib & Dexamethasone x 2

Targeted therapy

Bortezomib (Velcade) 1 mg/m² IV once per day on days -6, -3, +1, +4

Chemotherapy

Melphalan (Alkeran) 70 mg/m² IV once per day on days -2 & -1

Stem cells re-infused on day 0

Regimen variant #2, HDM 200 mg/m²

Study	Evidence	Efficacy
Sanchorawala et al. 2015 (X05292)	Phase II	HRR: 77%

Preceding treatment

Bortezomib & Dexamethasone x 2

Targeted therapy

Bortezomib (Velcade) 1 mg/m² IV once per day on days -6, -3, +1, +4

Chemotherapy

Melphalan (Alkeran) 100 mg/m² IV once per day on days -2 & -1

Stem cells re-infused on day 0

References

X05292: Sanchorawala V, Brauneis D, Shelton AC, Lo S, Sun F, Sloan JM, Quillen K, Seldin DC. Induction therapy with bortezomib followed by bortezomib-high dose melphalan and stem cell transplantation for light chain amyloidosis: Results of a prospective clinical trial. Biol Blood Marrow Transplant. 2015 Aug;21(8):1445-51. Epub 2015 Apr 6. link to original article contains verified protocol PubMed

Melphalan, then auto HSCT

back to top

Regimen variant #1, 100 mg/m²

Study	Evidence
Landau et al. 2012 (NCT822)	Phase II, <20 pts

Note: this dose was intended for patients aged 61 to 70 with cardiac and/or renal compromise.

Chemotherapy

Melphalan (Alkeran) 100 mg/m² IV once (day not specified)

Stem cell re-infused on day not specified

Subsequent treatment

Less than CR: BD consolidation x 6

Regimen variant #2, 140 mg/m²

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Skinner et al. 2004	1994-2002	Case series
Jaccard et al. 2007	2000-2005	Phase III (E-esc)	M-DEX	Seems to have inferior OS
Landau et al. 2012 (NCT822)	2007-2011	Phase II, <20 pts
Huang et al. 2014 (NJCT-0703)	2009-2012	Non-randomized portion of RCT

Note: in Jaccard et al. 2007, this dose was intended for patients older than 65, with an EF below 30%, with a calculated CrCl of less than 30 ml per minute, or with severe liver disease. In NCT822, this dose was intended for patients up to age 60 with cardiac and/or renal compromise, or for patients aged 61 to 70 without cardiac or renal compromise. In NJCT-0703, this dose was intended for patients up to age 65 with cardiac or renal compromise.

Preceding treatment

NJCT-0703: BD x 2 versus no induction

Chemotherapy

Melphalan (Alkeran) 140 mg/m² IV once on day 0

Stem cell re-infused on day 2

Subsequent treatment

NCT822, less than CR: BD consolidation x 6

Regimen variant #3, 200 mg/m²

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Skinner et al. 2004	1994-2002	Phase II
Jaccard et al. 2007	2000-2005	Phase III (E-esc)	M-DEX	Seems to have inferior OS
Landau et al. 2012 (NCT822)	2007-2011	Phase II, <20 pts
Huang et al. 2014 (NJCT-0703)	2009-2012	Non-randomized portion of RCT

Note: in NCT822, this dose was intended for patients up to age 60 without cardiac or renal compromise. In NJCT-0703, this dose was intended for patients up to age 65 without cardiac or renal compromise.

Preceding treatment

NJCT-0703: BD x 2 versus no induction

Chemotherapy

Melphalan (Alkeran) 200 mg/m² IV once on day 0

Stem cell re-infused on day 2

Subsequent treatment

NCT822, less than CR: BD consolidation x 6

References

Skinner M, Sanchorawala V, Seldin DC, Dember LM, Falk RH, Berk JL, Anderson JJ, O'Hara C, Finn KT, Libbey CA, Wiesman J, Quillen K, Swan N, Wright DG. High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: an 8-year study. Ann Intern Med. 2004 Jan 20;140(2):85-93. link to original article contains verified protocol PubMed
Jaccard A, Moreau P, Leblond V, Leleu X, Benboubker L, Hermine O, Recher C, Asli B, Lioure B, Royer B, Jardin F, Bridoux F, Grosbois B, Jaubert J, Piette JC, Ronco P, Quet F, Cogne M, MAG; IFM. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med. 2007 Sep 13;357(11):1083-93. link to original article contains verified protocol PubMed NCT00344526
NCT822: Landau H, Hassoun H, Rosenzweig MA, Maurer M, Liu J, Flombaum C, Bello C, Hoover E, Riedel E, Giralt S, Comenzo RL. Bortezomib and dexamethasone consolidation following risk-adapted melphalan and stem cell transplantation for patients with newly diagnosed light-chain amyloidosis. Leukemia. 2013 Apr;27(4):823-8. Epub 2012 Sep 27. link to original article contains protocol PubMed
NJCT-0703: Huang X, Wang Q, Chen W, Zeng C, Chen Z, Gong D, Zhang H, Liu Z. Induction therapy with bortezomib and dexamethasone followed by autologous stem cell transplantation versus autologous stem cell transplantation alone in the treatment of renal AL amyloidosis: a randomized controlled trial. BMC Med. 2014 Jan 6;12:2. link to original article link to PMC article contains protocol PubMed NCT01998503

VD

back to top

VD: Velcade (Bortezomib) & Dexamethasone
BD: Bortezomib & Dexamethasone

Regimen

Study	Evidence
Landau et al. 2012 (NCT822)	Phase II

Preceding treatment

High-dose melphalan with autologous hematopoietic stem cell transplant, with less than CR

Targeted therapy

Bortezomib (Velcade) as follows:
- Cycles 1 & 2: 1.3 mg/m² IV once per day on days 1, 4, 8, 11
- Cycles 2 to 6: 1.3 mg/m² IV once per day on days 1, 8, 15, 22
Dexamethasone (Decadron) as follows:
- Cycles 1 & 2: 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
- Cycles 2 to 6: 20 mg PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23

21-day cycle for 2 cycles, then 35-day cycle for 4 cycles (6 total)

References

NCT822: Landau H, Hassoun H, Rosenzweig MA, Maurer M, Liu J, Flombaum C, Bello C, Hoover E, Riedel E, Giralt S, Comenzo RL. Bortezomib and dexamethasone consolidation following risk-adapted melphalan and stem cell transplantation for patients with newly diagnosed light-chain amyloidosis. Leukemia. 2013 Apr;27(4):823-8. Epub 2012 Sep 27. link to original article contains verified protocol PubMed

Maintenance after first-line therapy

Rd

back to top

Rd: Revlimid (Lenalidomide) & low-dose dexamethasone
RevDex: Revlimid (Lenalidomide) & Dexamethasone
Ld: Lenalidomide & low-dose dexamethasone
LenDex: Lenalidomide & Dexamethasone

Regimen

Study	Evidence
Cibeira et al. 2015 (LENDEXAL)	Phase II

Preceding treatment

LDC x 12

Targeted therapy

Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4

Supportive medications

Aspirin 100 mg PO once per day or Low molecular weight heparin

28-day cycle for 39 cycles (3 years)

References

LENDEXAL: Cibeira MT, Oriol A, Lahuerta JJ, Mateos MV, de la Rubia J, Hernández MT, Granell M, Fernández de Larrea C, San Miguel JF, Bladé J; PETHEMA. A phase II trial of lenalidomide, dexamethasone and cyclophosphamide for newly diagnosed patients with systemic immunoglobulin light chain amyloidosis. Br J Haematol. 2015 Sep;170(6):804-13. Epub 2015 May 14. link to original article contains verified protocol PubMed

Relapsed or refractory

Bendamustine & Dexamethasone

back to top

Regimen

Study	Evidence
Lentzsch et al. 2020 (AAAJ7800)	Phase II

Chemotherapy

Bendamustine 100 mg/m² IV once per day on days 1 & 2
Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22

28-day cycle for up to 6 cycles or progression of disease

References

AAAJ7800: Lentzsch S, Lagos GG, Comenzo RL, Zonder JA, Osman K, Pan S, Bhutani D, Pregja S, Sanchorawala V, Landau H. Bendamustine With Dexamethasone in Relapsed/Refractory Systemic Light-Chain Amyloidosis: Results of a Phase II Study. J Clin Oncol. 2020 Feb 21 [Epub ahead of print] link to original article contains verified protocol PubMed

Bortezomib monotherapy

back to top

Regimen variant #1, twice per week

Study	Evidence
Reece et al. 2011 (CAN2007)	Phase II

Targeted therapy

Bortezomib (Velcade) 1.3 mg/m² (route not specified) once per day on days 1, 4, 8, 11

21-day cycle for up to 8 cycles, with extended treatment allowed for patients with clear clinical benefit

Regimen variant #2, weekly schedule

Study	Evidence
Reece et al. 2011 (CAN2007)	Phase II

Targeted therapy

Bortezomib (Velcade) 1.6 mg/m² (route not specified) once per day on days 1, 8, 15, 22

35-day cycle for up to 8 cycles, with extended treatment allowed for patients with clear clinical benefit

References

CAN2007: Reece DE, Hegenbart U, Sanchorawala V, Merlini G, Palladini G, Bladé J, Fermand JP, Hassoun H, Heffner L, Vescio RA, Liu K, Enny C, Esseltine DL, van de Velde H, Cakana A, Comenzo RL. Efficacy and safety of once-weekly and twice-weekly bortezomib in patients with relapsed systemic AL amyloidosis: results of a phase 1/2 study. Blood. 2011 Jul 28;118(4):865-73. Epub 2011 May 11. link to original article contains verified protocol PubMed
1. Update: Reece DE, Hegenbart U, Sanchorawala V, Merlini G, Palladini G, Bladé J, Fermand JP, Hassoun H, Heffner L, Kukreti V, Vescio RA, Pei L, Enny C, Esseltine DL, van de Velde H, Cakana A, Comenzo RL. Long-term follow-up from a phase 1/2 study of single-agent bortezomib in relapsed systemic AL amyloidosis. Blood. 2014 Oct 16;124(16):2498-506. Epub 2014 Sep 8. link to original article contains verified protocol link to PMC article PubMed

CRd

back to top

CRd: Cyclophosphamide, Revlimid (Lenalidomide), low-dose dexamethasone
CLD: Cyclophosphamide, Lenalidomide Dexamethasone
RdC: Revlimid (Lenalidomide), low-dose dexamethasone, Cyclophosphamide

Regimen variant #1

Study	Evidence
Kumar et al. 2012	Phase II
Palladini et al. 2012 (AC-003-IT)	Phase II

Chemotherapy

Cyclophosphamide (Cytoxan) 500 mg PO once per day on days 1, 8, 15

Targeted therapy

Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 21
Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22
- In AC-003-IT only, patients who retained over 3% body weight despite "optimal diuretic use" received 20 mg PO once per day on days 1, 8, 15, 22

Supportive medications

(varies depending on reference)

Thromboprophylaxis with one of the following:
- Standard patients: Aspirin 81 to 325 mg PO once per day
- In Kumar et al. 2012, patients with previous thrombotic histories or who were considered to be higher thrombotic risks were recommended to receive: low molecular weight heparin or Warfarin (Coumadin)
Kumar et al. 2012: "Routine antibiotic, antiviral, or antifungal prophylaxis was not mandated and left to the discretion of the treating physician."

28-day cycle for up to 9 cycles or 2 years, depending on reference

Regimen variant #2

Study	Evidence	Efficacy
Kastritis et al. 2012	Phase I/II	ORR: 55% (hematologic response) 22% (organ response)

This was the highest dose level tested, which had no dose-limiting toxicities.

Chemotherapy

Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 21

Targeted therapy

Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4
Cyclophosphamide (Cytoxan) 100 mg PO once per day on days 1 to 10

Supportive medications

Thromboprophylaxis: Aspirin 100 mg PO once per day
Proton pump inhibitor
Trimethoprim-sulfamethoxazole (Bactrim), dose and schedule not listed
Valacyclovir (Valtrex), dose and schedule not listed

28-day cycle for 12 cycles

References

Kumar SK, Hayman SR, Buadi FK, Roy V, Lacy MQ, Gertz MA, Allred J, Laumann KM, Bergsagel LP, Dingli D, Mikhael JR, Reeder CB, Stewart AK, Zeldenrust SR, Greipp PR, Lust JA, Fonseca R, Russell SJ, Rajkumar SV, Dispenzieri A. Lenalidomide, cyclophosphamide, and dexamethasone (CRd) for light-chain amyloidosis: long-term results from a phase 2 trial. Blood. 2012 May 24;119(21):4860-7. Epub 2012 Apr 13. link to original article contains verified protocol link to PMC article PubMed
Kastritis E, Terpos E, Roussou M, Gavriatopoulou M, Pamboukas C, Boletis I, Marinaki S, Apostolou T, Nikitas N, Gkortzolidis G, Michalis E, Delimpasi S, Dimopoulos MA. A phase 1/2 study of lenalidomide with low-dose oral cyclophosphamide and low-dose dexamethasone (RdC) in AL amyloidosis. Blood. 2012 Jun 7;119(23):5384-90. Epub 2012 Apr 18. link to original article contains verified protocol PubMed
AC-003-IT: Palladini G, Russo P, Milani P, Foli A, Lavatelli F, Nuvolone M, Perlini S, Merlini G. A phase II trial of cyclophosphamide, lenalidomide and dexamethasone in previously treated patients with AL amyloidosis. Haematologica. 2013 Mar;98(3):433-6. Epub 2012 Sep 14. link to original article contains verified protocol link to PMC article PubMed

CTD

back to top

CTD: Cyclophosphamide, Thalidomide, Dexamethasone

Regimen variant #1

Study	Evidence
Wechalekar et al. 2007	Phase II

Chemotherapy

Cyclophosphamide (Cytoxan) 500 mg PO once per day on days 1, 8, 15

Targeted therapy

Thalidomide (Thalomid) 100 mg PO once per day on days 1 to 21, then increased to 200 mg PO once per day on days 1 to 21 if well tolerated after 4 weeks
Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 9 to 12

Supportive medications

"Antimicrobial and thromboprophylaxis were given according to local protocol"; no routine thromboprophylaxis

21-day cycles, "given until a stable clonal response was achieved on consecutive samples at least 4 weeks apart" or until confirmed lack of response

Regimen variant #2, risk attenuated regimen

Study	Evidence
Wechalekar et al. 2007	Phase II

For elderly patients (age greater than 70 years), NYHA heart failure greater than class II, and those with significant fluid overload.

Chemotherapy

Cyclophosphamide (Cytoxan) 500 mg PO once per day on days 1, 8, 15

Targeted therapy

Thalidomide (Thalomid) as follows:
- Cycle 1: 50 mg PO once per day
- Cycle 2 (if tolerated): 100 mg PO once per day
- Cycle 3 (if tolerated): 150 mg PO once per day
- Cycle 4 onwards (if tolerated): 200 mg PO once per day
Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4, 15 to 18

Supportive medications

"Antimicrobial and thromboprophylaxis were given according to local protocol"; no routine thromboprophylaxis

28-day cycles, "given until a stable clonal response was achieved on consecutive samples at least 4 weeks apart" or until confirmed lack of response

References

Wechalekar AD, Goodman HJ, Lachmann HJ, Offer M, Hawkins PN, Gillmore JD. Safety and efficacy of risk-adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL amyloidosis. Blood. 2007 Jan 15;109(2):457-64. Epub 2006 Sep 21. link to original article contains verified protocol PubMed

Daratumumab monotherapy

back to top

Regimen

Study	Evidence
Kaufman et al. 2017	Retrospective

Targeted therapy

Daratumumab (Darzalex) as follows:
- Cycles 1 & 2: 16 mg/kg IV once per day on days 1, 8, 15, 22
- Cycles 3 & 4: 16 mg/kg IV once per day on days 1 & 15
- Cycle 5 onwards: 16 mg/kg IV once on day 1

Supportive medications

Acetaminophen (Tylenol) 650 mg PO once, prior to daratumumab
Diphenhydramine (Benadryl) 50 mg PO once, prior to daratumumab
Dexamethasone (Decadron) 20 mg IV or PO once, prior to daratumumab

Continued indefinitely

References

Retrospective: Kaufman GP, Schrier SL, Lafayette RA, Arai S, Witteles RM, Liedtke M. Daratumumab yields rapid and deep hematologic responses in patients with heavily pretreated AL amyloidosis. Blood. 2017 Aug 17;130(7):900-902. link to original article PubMed

Ixazomib monotherapy

back to top

Regimen

Study	Evidence
Sanchorawala et al. 2017	Phase I/II

This is the MTD dosing determined in this phase I/II trial.

Targeted therapy

Ixazomib (Ninlaro) 4 mg PO once per day on days 1, 8, 15

28-day cycle for up to 12 cycles or longer if patient was "deriving clinical benefit"

Subsequent treatment

Patients with less than PR after four cycles: Ixazomib & dexamethasone

References

Sanchorawala V, Palladini G, Kukreti V, Zonder JA, Cohen AD, Seldin DC, Dispenzieri A, Jaccard A, Schönland SO, Berg D, Yang H, Gupta N, Hui AM, Comenzo RL, Merlini G. A phase 1/2 study of the oral proteasome inhibitor ixazomib in relapsed or refractory AL amyloidosis. Blood. 2017 Aug 3;130(5):597-605. Epub 2017 May 26. link to original article contains verified protocol PubMed

Ixazomib & Dexamethasone

back to top

Regimen

Study	Evidence
Sanchorawala et al. 2017	Phase I/II

Preceding treatment

Ixazomib x 4, with less than PR

Targeted therapy

Ixazomib (Ninlaro) 4 mg PO once per day on days 1, 8, 15
Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4

28-day cycles

References

Sanchorawala V, Palladini G, Kukreti V, Zonder JA, Cohen AD, Seldin DC, Dispenzieri A, Jaccard A, Schönland SO, Berg D, Yang H, Gupta N, Hui AM, Comenzo RL, Merlini G. A phase 1/2 study of the oral proteasome inhibitor ixazomib in relapsed or refractory AL amyloidosis. Blood. 2017 Aug 3;130(5):597-605. Epub 2017 May 26. link to original article contains verified protocol PubMed

Pd

back to top

Pd: Pomalidomide & low-dose dexamethasone

Regimen variant #1

Study	Evidence
Palladini et al. 2017 (AC-007-IT)	Phase II

Targeted therapy

Pomalidomide (Pomalyst) 4 mg PO once per day
Dexamethasone (Decadron) 20 mg PO once per day on days 1, 8, 15, 22

28-day cycles

Regimen variant #2

Study	Evidence
Sanchorawala et al. 2016 (PO-AMYL-PI-0024)	Phase I/II, <20 pts

Note: although the trial enrolled 27 patients, only 18 were treated at the MTD reproduced here:

Targeted therapy

Pomalidomide (Pomalyst) 4 mg PO once per day on days 1 to 21
Dexamethasone (Decadron) 20 mg PO once per day on days 1, 8, 15, 22

28-day cycles

Regimen variant #3

Study	Evidence
Dispenzieri et al. 2012	Phase II

Targeted therapy

Pomalidomide (Pomalyst) 2 mg PO once per day
- See Dispenzieri et al. 2012 for dose escalations and reductions
Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22

Supportive medications

Thromboprophylaxis: Aspirin 325 mg PO once per day

28-day cycles

References

Dispenzieri A, Buadi F, Laumann K, LaPlant B, Hayman SR, Kumar SK, Dingli D, Zeldenrust SR, Mikhael JR, Hall R, Rajkumar SV, Reeder C, Fonseca R, Bergsagel PL, Stewart AK, Roy V, Witzig TE, Lust JA, Russell SJ, Gertz MA, Lacy MQ. Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. Blood. 2012 Jun 7;119(23):5397-404. Epub 2012 Apr 4. link to original article contains verified protocol link to PMC article PubMed
PO-AMYL-PI-0024: Sanchorawala V, Shelton AC, Lo S, Varga C, Sloan JM, Seldin DC. Pomalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 1 and 2 trial. Blood. 2016 Aug 25;128(8):1059-62. Epub 2016 Jul 5. link to original article contains verified protocol PubMed
AC-007-IT: Palladini G, Milani P, Foli A, Basset M, Russo F, Perlini S, Merlini G. A phase 2 trial of pomalidomide and dexamethasone rescue treatment in patients with AL amyloidosis. Blood. 2017 Apr 13;129(15):2120-2123. Epub 2017 Jan 27. link to original article contains verified protocol PubMed

Rd

back to top

Rd: Revlimid (Lenalidomide) & low-dose dexamethasone
RevDex: Revlimid (Lenalidomide) & Dexamethasone
Ld: Lenalidomide & low-dose dexamethasone
LenDex: Lenalidomide & Dexamethasone

Regimen variant #1, weekly dexamethasone

Study	Evidence
Palladini et al. 2012	Phase II

Targeted therapy

Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 21
Dexamethasone (Decadron) 20 mg PO once per day on days 1, 8, 15, 22

Supportive medications

Thromboprophylaxis: Aspirin 100 mg PO once per day
Omeprazole (Prilosec) 20 mg PO once per day

28-day cycles

Regimen variant #2, pulsed dexamethasone

Study	Evidence
Sanchorwala et al. 2006	Phase II

Preceding treatment

Treatment failure after lenalidomide x 3 cycles

Targeted therapy

Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 21
Dexamethasone (Decadron) as follows:
- Odd cycles: 10 to 20 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20

Supportive medications

Thromboprophylaxis: Aspirin 81 or 325 mg PO once per day
Proton pump inhibitor

28-day cycles

References

Sanchorawala V, Wright DG, Rosenzweig M, Finn KT, Fennessey S, Zeldis JB, Skinner M, Seldin DC. Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial. Blood. 2007 Jan 15;109(2):492-6. Epub 2006 Sep 7. link to original article contains verified protocol PubMed
Palladini G, Russo P, Foli A, Milani P, Lavatelli F, Obici L, Nuvolone M, Brugnatelli S, Invernizzi R, Merlini G. Salvage therapy with lenalidomide and dexamethasone in patients with advanced AL amyloidosis refractory to melphalan, bortezomib, and thalidomide. Ann Hematol. 2012 Jan;91(1):89-92. link to original article contains verified protocol PubMed

RD

back to top

RD: Revlimid (Lenalidomide) & high-dose Dexamethasone

Regimen

Study	Evidence
Dispenzieri et al. 2006	Phase II

Preceding treatment

Treatment failure after lenalidomide x 3 cycles

Targeted therapy

Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 15 to 18

28-day cycle for 12 or more cycles

References

Dispenzieri A, Lacy MQ, Zeldenrust SR, Hayman SR, Kumar SK, Geyer SM, Lust JA, Allred JB, Witzig TE, Rajkumar SV, Greipp PR, Russell SJ, Kabat B, Gertz MA. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood. 2007 Jan 15;109(2):465-70. Epub 2006 Sep 28. link to original article contains verified protocol PubMed

Light-chain (AL) amyloidosis

Guidelines

BSH

EMN

NCCN

First-line therapy (including transplant ineligible)

Colchicine monotherapy

Regimen

Chemotherapy

References

CRd

Regimen variant #1, "LDC"

Chemotherapy

Supportive medications

Subsequent treatment

Regimen variant #2, "CRd"

Chemotherapy

Supportive medications

Regimen variant #3, "RdC"

Chemotherapy

Supportive medications

References

CTD

Regimen variant #1

Chemotherapy

Supportive medications

Regimen variant #2, risk attenuated regimen

Chemotherapy

Supportive medications

References

Dara-CyBorD

Regimen

Targeted therapy

Chemotherapy

Subsequent treatment

References

Lenalidomide monotherapy

Regimen variant #1, 15 mg dosing

Chemotherapy

Supportive medications

Subsequent treatment

Regimen variant #2, 25 mg dosing

Chemotherapy

Subsequent treatment

References

M-DEX

Regimen variant #1, BSA-based melphalan

Chemotherapy

Supportive medications

Regimen variant #2, weight-based melphalan

Chemotherapy

Supportive medications

References

MP

Regimen

Chemotherapy

References

MRD

Regimen variant #1, "L-M-Dex"

Chemotherapy

Supportive medications

Regimen variant #2

Chemotherapy

Supportive medications

Regimen variant #3

Chemotherapy

Supportive medications

References

No induction

Regimen

Subsequent treatment

References

VD

Regimen variant #1, lower-dose dex

Chemotherapy

Supportive medications

Subsequent treatment

Regimen variant #2, higher-dose dex

Chemotherapy

Subsequent treatment

Regimen variant #1, HDM 140 mg/m²

Regimen variant #2, HDM 200 mg/m²

Regimen variant #1, 100 mg/m²

Regimen variant #2, 140 mg/m²

Regimen variant #3, 200 mg/m²