Section editor
	Samuel M. Rubinstein, MD University of North Carolina Chapel Hill, NC, USA LinkedIn

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25 regimens on this page 48 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.

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)

CRd

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

Regimen variant #1, "LDC"

Study	Dates of enrollment	Evidence
Cibeira et al. 2015 (LENDEXAL)	2010-2012	Phase 2

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

Glucocorticoid therapy

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

Targeted therapy

Lenalidomide (Revlimid) by the following renal function-based criteria:
- eGFR 50 mL/min/1.73 m² or more: 15 mg PO once per day on days 1 to 21
- eGFR 30 up to 50 mL/min/1.73 m²: 10 mg PO once per day on days 1 to 21
- eGFR less than 30 mL/min/1.73 m²: 5 mg PO once per day on days 1 to 21

Supportive therapy

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

28-day cycle for 12 cycles

Subsequent treatment

LENDEXAL, patients without progression who were tolerating therapy: Rd maintenance

Dose and schedule modifications

Cardiac stage III (this is not defined): Dexamethasone (Decadron) upfront modification "allowed" but not defined

Regimen variant #2, "CRd"

Study	Dates of enrollment	Evidence
Kumar et al. 2012 (MC0685)	2007-2008	Phase 2

Chemotherapy

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

Glucocorticoid therapy

Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22

Targeted therapy

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

Supportive therapy

Thromboprophylaxis by the following criteria:
- 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	Dates of enrollment	Evidence
Kastritis et al. 2012 (RV-178)	2008-2011	Phase 1/2

Note: This was the highest dose level tested in RV-178, which had no dose-limiting toxicities.

Chemotherapy

Cyclophosphamide (Cytoxan) 100 mg PO once per day on days 1 to 10

Glucocorticoid therapy

Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4

Targeted therapy

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

Supportive therapy

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

MC0685: 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 dosing details in manuscript link to PMC article PubMed NCT00564889
RV-178: 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 dosing details in manuscript PubMed NCT00981708
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 dosing details in manuscript PubMed NCT01194791

CTD

CTD: Cyclophosphamide, Thalidomide, Dexamethasone

Regimen variant #1

Study	Dates of enrollment	Evidence
Wechalekar et al. 2007	2000-2005	Phase 2

Note: Thalidomide dose was increased only if the prior dose was tolerated.

Chemotherapy

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

Glucocorticoid therapy

Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 9 to 12

Targeted therapy

Thalidomide (Thalomid) as follows:
- Cycle 1: 100 mg PO once per day on days 1 to 21
- Cycle 2: 100 mg PO once per day on days 1 to 7, then 200 mg PO once per day on days 8 to 21
- Cycle 3 onwards: 200 mg PO once per day on days 1 to 21

Supportive therapy

"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	Dates of enrollment	Evidence
Wechalekar et al. 2007	2000-2005	Phase 2

Note: Thalidomide dose was increased only if the prior dose was tolerated.

Eligibility criteria

Older 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

Glucocorticoid therapy

Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4, 15 to 18

Targeted therapy

Thalidomide (Thalomid) as follows:
- Cycle 1: 50 mg PO once per day on days 1 to 28
- Cycle 2: 100 mg PO once per day on days 1 to 28
- Cycle 3: 150 mg PO once per day on days 1 to 28
- Cycle 4 onwards: 200 mg PO once per day on days 1 to 28

Supportive therapy

"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 dosing details in manuscript PubMed

Dara-CyBorD

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

Synopsis

Introduction: The evolution of front line therapy with Dara-VCd (daratumumab, bortezomib, cyclophosphamide, and dexamethasone) for AL amyloidosis has progressed through several stages, involving a shift from traditional treatment approaches to the incorporation of monoclonal antibodies with established therapy regimens. This summary highlights the key developments in the use of Dara-VCd as a front line therapy for AL amyloidosis, supported by relevant literature.

Initial Combination Therapy: The combination of bortezomib, cyclophosphamide, and dexamethasone (VCd) emerged as a standard of care for the treatment of AL amyloidosis, demonstrating high rates of hematologic response and organ improvement (Mikhael et al, 2012 [1]).

Introduction of Daratumumab: Daratumumab, a monoclonal antibody targeting CD38, demonstrated significant efficacy as a single agent in relapsed/refractory multiple myeloma (Lonial et al., 2016 [2]). The success of daratumumab led to its incorporation into combination regimens for other plasma cell disorders, such as AL amyloidosis. Daratumumab as monotherapy also demonstrated high rates of hematologic and organ response when used to treat patients with relapsed AL amyloid (Sanchorawala et al, 2020 [3] ), which resulted in daratumumab being investigated frontline in combination with VCd.

Development of Dara-VCd: The addition of daratumumab to the VCd regimen (Dara-VCd) was investigated in the phase 3 ANDROMEDA trial, which compared Dara-VCd to VCd alone in newly diagnosed AL amyloidosis patients (Palladini et al., 2020 [4]). The trial results demonstrated improved hematologic response rates, organ response rates, and progression-free survival for Dara-VCd (Kastritis et al., 2021 [5]), indicating its potential as a more effective front line therapy than VCd alone.

Approval of Dara-VCd: Based on the positive results from the ANDROMEDA trial, the FDA granted approval for Dara-VCd as a front line therapy for newly diagnosed AL amyloidosis patients on January 15, 2021 (FDA, 2021).

Conclusion: The evolution of front line therapy with Dara-VCd for AL amyloidosis has been marked by the successful integration of daratumumab with established treatment regimens, offering improved clinical outcomes for newly diagnosed patients.

Practical Considerations: Many practicing amyloid physicians will empirically reduce the dose of bortezomib from 1.3 mg/m2 to 1.0 mg/m2 weekly, and the dose of dexamethasone from 40 mg PO/IV weekly to 20 mg PO/IV weekly, to minimize the risk of decompensated heart failure in patients with advanced cardiac amyloidosis.
The draft for this synopsis was generated by a large language model and then manually edited by the page editor for accuracy and style. See this page for more information about this pilot project.

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Kastritis et al. 2021 (ANDROMEDA)	2018-05-03 to 2019-08-15	Phase 3 (E-RT-esc)	CyBorD	Superior CHR (primary endpoint) CHR: 53.3% vs 18.1% (RR 2.9, 95% CI 2.1-4.1)

Note: the dexamethasone dose could be optionally reduced to 20 mg for patients who were older than 70, underweight, hypervolemic, with poorly controlled diabetes mellitus, or who had previous unacceptable side effects from corticosteroids.

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
- Cycles 7 up to 24: 1800 mg SC once on day 1
Bortezomib (Velcade) as follows:
- Cycles 1 to 6: 1.3 mg/m² SC once per day on days 1, 8, 15, 22

Chemotherapy

Cyclophosphamide (Cytoxan) as follows:
- Cycles 1 to 6: 300 mg/m² (maximum dose of 500 mg) PO or IV once per day on days 1, 8, 15, 22

Glucocorticoid therapy

Dexamethasone (Decadron) as follows:
- Cycles 1 to 6: 40 mg PO or IV once per day on days 1, 8, 15, 22 (see note)

28-day cycle for up to 24 cycles

References

ANDROMEDA: Kastritis E, Palladini G, Minnema MC, Wechalekar AD, Jaccard A, Lee HC, Sanchorawala V, Gibbs S, Mollee P, Venner CP, Lu J, Schönland S, Gatt ME, Suzuki K, Kim K, Cibeira MT, Beksac M, Libby E, Valent J, Hungria V, Wong SW, Rosenzweig M, Bumma N, Huart A, Dimopoulos MA, Bhutani D, Waxman AJ, Goodman SA, Zonder JA, Lam S, Song K, Hansen T, Manier S, Roeloffzen W, Jamroziak K, Kwok F, Shimazaki C, Kim JS, Crusoe E, Ahmadi T, Tran N, Qin X, Vasey SY, Tromp B, Schecter JM, Weiss BM, Zhuang SH, Vermeulen J, Merlini G, Comenzo RL; ANDROMEDA Trial Investigators. Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis. N Engl J Med. 2021 Jul 1;385(1):46-58. link to original article contains dosing details in manuscript PubMed NCT03201965

Doxycycline-CyBorD

Doxycycline-CyBorD: Doxycycline, Cyclophosphamide, Bortezomib, Dexamethasone

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Shen et al. 2021 (PUMCH-AL2017)	2018-2019	Randomized Phase 2 (E-esc)	CyBorD	Did not meet primary endpoint of cardiac PFS (HR 0.91, 95% CI 0.54-1.55)

Targeted therapy

Doxycycline 100 mg PO twice per day
Bortezomib (Velcade) 1.3 mg/m² SC once per day on days 1, 8, 15, 22

Chemotherapy

Cyclophosphamide (Cytoxan) 300 mg/m² (maximum dose of 500 mg) PO or IV once per day on days 1, 8, 15, 22

Glucocorticoid therapy

Dexamethasone (Decadron) 40 mg PO or IV once per day on days 1, 8, 15, 22

28-day cycle for 9 cycles

References

PUMCH-AL2017: Shen KN, Fu WJ, Wu Y, Dong YJ, Huang ZX, Wei YQ, Li CR, Sun CY, Chen Y, Miao HL, Zhang YL, Cao XX, Zhou DB, Li J. Doxycycline Combined With Bortezomib-Cyclophosphamide-Dexamethasone Chemotherapy for Newly Diagnosed Cardiac Light-Chain Amyloidosis: A Multicenter Randomized Controlled Trial. Circulation. 2022 Jan 4;145(1):8-17. Epub 2021 Sep 10. link to original article contains dosing details in manuscript PubMed NCT03401372

Lenalidomide monotherapy

Regimen variant #1, 15 mg dosing

Study	Dates of enrollment	Evidence
Sanchorwala et al. 2006	2004-2006	Phase 2

Note: 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.

Targeted therapy

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

Supportive therapy

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	Dates of enrollment	Evidence
Dispenzieri et al. 2006 (MC0484)	2004-2005	Phase 2

Targeted therapy

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 dosing details in manuscript 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
MC0484: 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 dosing details in manuscript PubMed

Melphalan & Dexamethasone

M-DEX: Melphalan & DEXamethasone

Regimen variant #1, BSA-based melphalan

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Jaccard et al. 2007 (I00001)	2000-2005	Phase 3 (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 in this context, prior to becoming a standard comparator arm.

Chemotherapy

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

Glucocorticoid therapy

Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4

Supportive therapy

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	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Palladini et al. 2003	1999-2002	Phase 2
Kastritis et al. 2020 (EMN-03)	2011-2016	Phase 3 (C)	BMDex	Inferior OS

Chemotherapy

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

Glucocorticoid therapy

Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4

Supportive therapy

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 dosing details in manuscript 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
I00001: 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 dosing details in manuscript 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 dosing details in manuscript PubMed NCT01277016

MRD

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

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

Study	Dates of enrollment	Evidence
Hegenbart et al. 2017 (LEOMEX)	2009-2012	Phase 2

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

Melphalan (Alkeran) 0.15 mg/kg PO once per day on days 1 to 4

Glucocorticoid therapy

Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4

Targeted therapy

Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21

28-day cycle for 6 cycles

Supportive therapy

Thromboprophylaxis by the following risk-based criteria:
- 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	Dates of enrollment	Evidence
Sanchorwala et al. 2012 (RV-AMYL-PI-0219)	2008-2011	Phase 2, fewer than 20 pts

Note: 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

Glucocorticoid therapy

Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22

Targeted therapy

Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21

Supportive therapy

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	Dates of enrollment	Evidence
Moreau et al. 2010 (BRD 07/7-G)	2008-2009	Phase 1/2

Note: This is the MTD dosing.

Chemotherapy

Melphalan (Alkeran) 0.18 mg/kg PO once per day on days 1 to 4

Glucocorticoid therapy

Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4

Targeted therapy

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

Supportive therapy

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

28-day cycle for up to 9 cycles

References

BRD 07/7-G: 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 dosing details in manuscript PubMed NCT00621400
RV-AMYL-PI-0219: 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 dosing details in manuscript link to PMC article PubMed NCT00679367
LEOMEX: 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 dosing details in manuscript link to PMC article PubMed NCT00883623

Bortezomib & Dexamethasone (Vd)

Vd: Velcade (Bortezomib) & low-dose dexamethasone

Regimen variant #1, lower-dose dex

Study	Dates of enrollment	Evidence	Efficacy
Sanchorawala et al. 2015 (X05292)	2010-2013	Phase 2	HRR: 77%
Minnema et al. 2019 (HOVON 104)	2012-2016	Phase 2	HRR: 80%

Targeted therapy

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

Glucocorticoid therapy

Dexamethasone (Decadron) 20 mg PO once per day on days 1, 4, 8, 11

Supportive therapy

21-day cycle for 2 cycles

Subsequent treatment

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

Regimen variant #2, higher-dose dex

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Huang et al. 2014 (NJCT-0703)	2009-2012	Randomized Phase 2 (E-esc)	No induction	Seems to have superior OS (secondary endpoint)

Targeted therapy

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

Glucocorticoid therapy

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 consolidation

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 dosing details in manuscript 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 dosing details in manuscript PubMed NCT01083316
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. Epub 2019 Mar 28. link to original article contains dosing details in manuscript link to PMC article PubMed NTR3220

VDC

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

Regimen variant #1, 300/1.3/40, uncapped cyclophosphamide

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.

Targeted therapy

Bortezomib (Velcade) 1.3 mg/m² SC once per day on days 1, 4, 8, 11

Glucocorticoid therapy

Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22

Chemotherapy

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

Supportive therapy

Antiviral prophylaxis

28-day cycle for 2 to 6 cycles

Regimen variant #2, 300/1.3/40, capped cyclophosphamide

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Gertz et al. 2023 (VITAL)	2016-2018	Phase 3 (C)	SOC & Birtamimab	Did not meet composite primary endpoint
Kastritis et al. 2021 (ANDROMEDA)	2018-05-03 to 2019-08-15	Phase 3 (C)	Dara-CyBorD	Inferior CHR

Note: in ANDROMEDA, the dexamethasone dose could be optionally reduced to 20 mg for patients who were older than 70, underweight, hypervolemic, with poorly controlled diabetes mellitus, or who had previous unacceptable side effects from corticosteroids. VITAL did not specify dosing or further details of the treatment regimen; this was the most commonly given regimen for the standard-of-care.

Targeted therapy

Bortezomib (Velcade) 1.3 mg/m² SC once per day on days 1, 8, 15, 22

Chemotherapy

Cyclophosphamide (Cytoxan) 300 mg/m² (maximum dose of 500 mg) PO or IV once per day on days 1, 8, 15, 22

Glucocorticoid therapy

Dexamethasone (Decadron) 40 mg PO or IV once per day on days 1, 8, 15, 22 (see note)

28-day cycle for 6 cycles

Regimen variant #3, 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.

Targeted therapy

Bortezomib (Velcade) 1.5 mg/m² SC once per day on days 1, 8, 15, 22

Glucocorticoid therapy

Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22

Chemotherapy

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

Supportive therapy

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 dosing details in manuscript 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
ANDROMEDA: Kastritis E, Palladini G, Minnema MC, Wechalekar AD, Jaccard A, Lee HC, Sanchorawala V, Gibbs S, Mollee P, Venner CP, Lu J, Schönland S, Gatt ME, Suzuki K, Kim K, Cibeira MT, Beksac M, Libby E, Valent J, Hungria V, Wong SW, Rosenzweig M, Bumma N, Huart A, Dimopoulos MA, Bhutani D, Waxman AJ, Goodman SA, Zonder JA, Lam S, Song K, Hansen T, Manier S, Roeloffzen W, Jamroziak K, Kwok F, Shimazaki C, Kim JS, Crusoe E, Ahmadi T, Tran N, Qin X, Vasey SY, Tromp B, Schecter JM, Weiss BM, Zhuang SH, Vermeulen J, Merlini G, Comenzo RL; ANDROMEDA Trial Investigators. Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis. N Engl J Med. 2021 Jul 1;385(1):46-58. link to original article contains dosing details in manuscript PubMed NCT03201965
PUMCH-AL2017: Shen KN, Fu WJ, Wu Y, Dong YJ, Huang ZX, Wei YQ, Li CR, Sun CY, Chen Y, Miao HL, Zhang YL, Cao XX, Zhou DB, Li J. Doxycycline Combined With Bortezomib-Cyclophosphamide-Dexamethasone Chemotherapy for Newly Diagnosed Cardiac Light-Chain Amyloidosis: A Multicenter Randomized Controlled Trial. Circulation. 2022 Jan 4;145(1):8-17. Epub 2021 Sep 10. link to original article PubMed NCT03401372
VITAL: Gertz MA, Cohen AD, Comenzo RL, Kastritis E, Landau HJ, Libby EN, Liedtke M, Sanchorawala V, Schönland S, Wechalekar A, Zonder JA, Palladini G, Walling J, Guthrie S, Nie C, Karp C, Jin Y, Kinney GG, Merlini G. Birtamimab plus standard of care in light-chain amyloidosis: the phase 3 randomized placebo-controlled VITAL trial. Blood. 2023 Oct 5;142(14):1208-1218. link to original article PubMed NCT02312206

VMD

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

Regimen variant #1, 8 cycles

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Kastritis et al. 2020 (EMN-03)	2011-2016	Phase 3 (E-esc)	MDex	Superior OS (secondary endpoint) Median OS: NYR vs 34 mo (HR 0.50, 95% CI 0.27-0.90) Superior hematologic RR at 3 months (primary endpoint)

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

Targeted therapy

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

Chemotherapy

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

Glucocorticoid therapy

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 2

Note: this abstract is no longer available online.

Targeted therapy

Bortezomib (Velcade) given first, by the following symptom-based criteria:
- 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

Chemotherapy

Melphalan (Alkeran) given third, by the following renal function-based criteria:
- Serum creatinine 2.5 mg/dL or less: 9 mg/m² PO once per day on days 1 to 4
- Serum creatinine more than 2.5 mg/dL: 6 mg/m² PO once per day on days 1 to 4

Glucocorticoid therapy

Dexamethasone (Decadron) given second, by the following age- and comorbidity-based criteria:
- 70 years old or younger AND no peripheral edema AND no congestive heart failure (CHF): 40 mg IV or PO once per day on days 1, 8, 15, 22
- Older than 70 years old OR 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 dosing details in manuscript PubMed NCT01277016

Consolidation after first-line therapy

Bortezomib & Melphalan, then auto HSCT

Regimen variant #1, HDM 140 mg/m²

Study	Dates of enrollment	Evidence	Efficacy
Sanchorawala et al. 2015 (X05292)	2010-2013	Phase 2	HRR: 77%

Preceding treatment

Bortezomib & Dexamethasone induction 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

Supportive therapy

Autologous stem cells re-infused on day 0

One course

Regimen variant #2, HDM 200 mg/m²

Study	Dates of enrollment	Evidence	Efficacy
Sanchorawala et al. 2015 (X05292)	2010-2013	Phase 2	HRR: 77%

Preceding treatment

Bortezomib & Dexamethasone induction 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
- Roussel et al. 2009 gave as a single 200 mg/m² dose on day -2

Supportive therapy

Autologous stem cells re-infused on day 0

One course

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 dosing details in manuscript PubMed NCT01083316

Melphalan monotherapy, then auto HSCT

Regimen variant #1, 100 mg/m²

Study	Dates of enrollment	Evidence
Landau et al. 2012 (NCT-822)	2007-2011	Phase 2, fewer than 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

NCT-822, less than CR: BD consolidation x 6

Regimen variant #2, 140 mg/m²

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Skinner et al. 2004	1994-2002	Case series
Jaccard et al. 2007 (I00001)	2000-2005	Phase 3 (E-esc)	M-DEX	Seems to have inferior OS (primary endpoint)
Landau et al. 2012 (NCT-822)	2007-2011	Phase 2, fewer than 20 pts
Huang et al. 2014 (NJCT-0703)	2009-2012	Non-randomized part of phase 2 RCT

Note: in I00001, 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 NCT-822, 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

NCT-822, less than CR: BD consolidation x 6

Regimen variant #3, 200 mg/m²

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Skinner et al. 2004	1994-2002	Case series
Jaccard et al. 2007 (I00001)	2000-2005	Phase 3 (E-esc)	M-DEX	Seems to have inferior OS (primary endpoint)
Landau et al. 2012 (NCT-822)	2007-2011	Phase 2, fewer than 20 pts
Huang et al. 2014 (NJCT-0703)	2009-2012	Non-randomized part of phase 2 RCT

Note: in NCT-822, 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

NCT-822, 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 dosing details in manuscript PubMed
I00001: 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 dosing details in manuscript PubMed NCT00344526
NCT-822: 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 dosing details in abstract 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 dosing details in manuscript PubMed NCT01998503

Bortezomib & Dexamethasone (Vd)

Vd: Velcade (Bortezomib) & low-dose dexamethasone
BD: Bortezomib & Dexamethasone

Regimen

Study	Dates of enrollment	Evidence
Landau et al. 2012 (NCT-822)	2007-2011	Phase 2

Preceding treatment

High-dose melphalan with autologous hematopoietic stem cell transplant consolidation, 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 3 to 6: 1.3 mg/m² IV once per day on days 1, 8, 15, 22

Glucocorticoid therapy

Dexamethasone (Decadron) as follows:
- Cycles 1 & 2: 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
- Cycles 3 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

NCT-822: 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 dosing details in manuscript PubMed

Maintenance after first-line therapy

Lenalidomide & Dexamethasone (Rd)

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

Regimen

Study	Dates of enrollment	Evidence
Cibeira et al. 2015 (LENDEXAL)	2010-2012	Phase 2

Preceding treatment

LDC induction x 12

Targeted therapy

Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21

Glucocorticoid therapy

Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4

Supportive therapy

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 dosing details in manuscript PubMed NCT01194791

Relapsed or refractory

Bendamustine & Dexamethasone

Regimen

Study	Dates of enrollment	Evidence
Lentzsch et al. 2020 (AAAJ7800)	2013-2016	Phase 2

Chemotherapy

Bendamustine 100 mg/m² IV once per day on days 1 & 2

Glucocorticoid therapy

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 May 1;38(13):1455-1462. Epub 2020 Feb 21 link to original article contains dosing details in manuscript link to PMC article PubMed NCT01222260

Bortezomib monotherapy

Regimen variant #1, twice per week

Study	Dates of enrollment	Evidence
Reece et al. 2011 (CAN2007)	2005-2009	Phase 2

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	Dates of enrollment	Evidence
Reece et al. 2011 (CAN2007)	2005-2009	Phase 2

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 dosing details in manuscript PubMed NCT00298766
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 dosing details in manuscript link to PMC article PubMed

CRd

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

Regimen variant #1

Study	Dates of enrollment	Evidence
Kumar et al. 2012 (MC0685)	2007-2008	Phase 2
Palladini et al. 2012 (AC-003-IT)	2008-2009	Phase 2

Chemotherapy

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

Glucocorticoid therapy

Dexamethasone (Decadron) by the following study-specific criteria:
- MC0685 & AC-003-IT, standard patients: 40 mg PO once per day on days 1, 8, 15, 22
- AC-003-IT, patients who retained over 3% body weight despite "optimal diuretic use": 20 mg PO once per day on days 1, 8, 15, 22

Targeted therapy

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

Supportive therapy

(varies depending on reference)

Thromboprophylaxis with one of the following:
- Standard patients: Aspirin 81 to 325 mg PO once per day
- In MC0685, 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)
MC0685: "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 (AC-003-IT) or 2 years (MC0685)

Regimen variant #2

Study	Dates of enrollment	Evidence	Efficacy
Kastritis et al. 2012 (RV-178)	2008-2011	Phase 1/2	ORR: 55% (hematologic response) 22% (organ response)

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

Glucocorticoid therapy

Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4

Chemotherapy

Cyclophosphamide (Cytoxan) 100 mg PO once per day on days 1 to 10

Targeted therapy

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

Supportive therapy

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

MC0685: 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 dosing details in manuscript link to PMC article PubMed NCT00564889
RV-178: 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 dosing details in manuscript PubMed NCT00981708
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 dosing details in manuscript link to PMC article PubMed NCT00607581

CTD

CTD: Cyclophosphamide, Thalidomide, Dexamethasone

Regimen variant #1

Study	Dates of enrollment	Evidence
Wechalekar et al. 2007	2000-2005	Phase 2

Note: Thalidomide dose was increased only if the prior dose was tolerated.

Chemotherapy

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

Glucocorticoid therapy

Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 9 to 12

Targeted therapy

Thalidomide (Thalomid) as follows:
- Cycle 1: 100 mg PO once per day on days 1 to 21
- Cycle 2: 100 mg PO once per day on days 1 to 7, then 200 mg PO once per day on days 8 to 21
- Cycle 3 onwards: 200 mg PO once per day on days 1 to 21

Supportive therapy

"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	Dates of enrollment	Evidence
Wechalekar et al. 2007	2000-2005	Phase 2

Note: Thalidomide dose was increased only if the prior dose was tolerated.

Eligibility criteria

Older 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

Glucocorticoid therapy

Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4, 15 to 18

Targeted therapy

Thalidomide (Thalomid) as follows:
- Cycle 1: 50 mg PO once per day on days 1 to 28
- Cycle 2: 100 mg PO once per day on days 1 to 28
- Cycle 3: 150 mg PO once per day on days 1 to 28
- Cycle 4 onwards: 200 mg PO once per day on days 1 to 28

Supportive therapy

"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 dosing details in manuscript PubMed

Cyclophosphamide & Dexamethasone

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Dispenzieri et al. 2021 (Tourmaline-AL1)	2012-2018	Phase 3 (C)	Ixazomib & Dexamethasone	Did not meet primary endpoint of HRR

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

Chemotherapy

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

Glucocorticoid therapy

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

28-day cycles

References

Tourmaline-AL1: Dispenzieri A, Kastritis E, Wechalekar AD, Schönland SO, Kim K, Sanchorawala V, Landau HJ, Kwok F, Suzuki K, Comenzo RL, Berg D, Liu G, Kumar A, Faller DV, Merlini G. A randomized phase 3 study of ixazomib-dexamethasone versus physician's choice in relapsed or refractory AL amyloidosis. Leukemia. 2022 Jan;36(1):225-235. Epub 2021 Jun 24. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01659658
1. HRQoL analysis: Sanchorawala V, Wechalekar AD, Kim K, Schönland SO, Landau HJ, Kwok F, Suzuki K, Dispenzieri A, Merlini G, Comenzo RL, Cherepanov D, Hayden VC, Kumar A, Labotka R, Faller DV, Kastritis E. Quality of life and symptoms among patients with relapsed/refractory AL amyloidosis treated with ixazomib-dexamethasone versus physician's choice. Am J Hematol. 2023 May;98(5):720-729. Epub 2023 Feb 14. link to original article PubMed

Daratumumab monotherapy

Regimen variant #1, 6 months

Study	Dates of enrollment	Evidence
Roussel et al. 2020 (AMYDARA)	2016-2018	Phase 2

Targeted therapy

Daratumumab (Darzalex) as follows:
- Cycles 1 to 4: 16 mg/kg IV once per day on days 1 & 8
- Cycles 5 to 12: 16 mg/kg IV once on day 1

Supportive therapy

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

14-day cycle for 12 cycles

Regimen variant #2, 2 years

Study	Dates of enrollment	Evidence
Sanchorawala et al. 2020 (H-35360)	2017-2018	Phase 2

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
- Cycles 5 to 24: 16 mg/kg IV once on day 1

Supportive therapy

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

28-day cycle for up to 24 cycles (up to 24 months total)

Regimen variant #3, indefinite

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 therapy

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

28-day cycles

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. Epub 2017 Jun 14. link to original article contains dosing details in manuscript PubMed
AMYDARA: Roussel M, Merlini G, Chevret S, Arnulf B, Stoppa AM, Perrot A, Palladini G, Karlin L, Royer B, Huart A, Macro M, Morel P, Frenzel L, Touzeau C, Boyle E, Dorvaux V, Le Bras F, Lavergne D, Bridoux F, Jaccard A. A prospective phase 2 trial of daratumumab in patients with previously treated systemic light-chain amyloidosis. Blood. 2020 Apr 30;135(18):1531-1540. link to original article contains dosing details in manuscript PubMed NCT02816476
H-35360: Sanchorawala V, Sarosiek S, Schulman A, Mistark M, Migre ME, Cruz R, Sloan JM, Brauneis D, Shelton AC. Safety, tolerability, and response rates of daratumumab in relapsed AL amyloidosis: results of a phase 2 study. Blood. 2020 Apr 30;135(18):1541-1547. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02841033

Dexamethasone monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Dispenzieri et al. 2021 (Tourmaline-AL1)	2012-2018	Phase 3 (C)	Ixazomib & Dexamethasone	Did not meet primary endpoint of HRR

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

Glucocorticoid therapy

Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20

28-day cycles

References

Tourmaline-AL1: Dispenzieri A, Kastritis E, Wechalekar AD, Schönland SO, Kim K, Sanchorawala V, Landau HJ, Kwok F, Suzuki K, Comenzo RL, Berg D, Liu G, Kumar A, Faller DV, Merlini G. A randomized phase 3 study of ixazomib-dexamethasone versus physician's choice in relapsed or refractory AL amyloidosis. Leukemia. 2022 Jan;36(1):225-235. Epub 2021 Jun 24. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01659658
1. HRQoL analysis: Sanchorawala V, Wechalekar AD, Kim K, Schönland SO, Landau HJ, Kwok F, Suzuki K, Dispenzieri A, Merlini G, Comenzo RL, Cherepanov D, Hayden VC, Kumar A, Labotka R, Faller DV, Kastritis E. Quality of life and symptoms among patients with relapsed/refractory AL amyloidosis treated with ixazomib-dexamethasone versus physician's choice. Am J Hematol. 2023 May;98(5):720-729. Epub 2023 Feb 14. link to original article PubMed

Ixazomib monotherapy

Regimen

Study	Dates of enrollment	Evidence
Sanchorawala et al. 2017 (C16007)	2012-NR	Phase 1/2

Note: This is the MTD dosing determined in this phase 1/2 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

C16007, patients with less than PR after four cycles: Ixazomib & dexamethasone intensification

References

C16007: 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 dosing details in manuscript link to PMC article PubMed NCT01318902

Ixazomib & Dexamethasone

Regimen

Study	Dates of enrollment	Evidence
Sanchorawala et al. 2017 (C16007)	2012-NR	Phase 1/2

Preceding treatment

Salvage Ixazomib x 4, with less than PR

Targeted therapy

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

Glucocorticoid therapy

Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4

28-day cycles

References

C16007: 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 dosing details in manuscript link to PMC article PubMed NCT01318902
Tourmaline-AL1: Dispenzieri A, Kastritis E, Wechalekar AD, Schönland SO, Kim K, Sanchorawala V, Landau HJ, Kwok F, Suzuki K, Comenzo RL, Berg D, Liu G, Kumar A, Faller DV, Merlini G. A randomized phase 3 study of ixazomib-dexamethasone versus physician's choice in relapsed or refractory AL amyloidosis. Leukemia. 2022 Jan;36(1):225-235. Epub 2021 Jun 24. link to original article link to PMC article PubMed NCT01659658
1. HRQoL analysis: Sanchorawala V, Wechalekar AD, Kim K, Schönland SO, Landau HJ, Kwok F, Suzuki K, Dispenzieri A, Merlini G, Comenzo RL, Cherepanov D, Hayden VC, Kumar A, Labotka R, Faller DV, Kastritis E. Quality of life and symptoms among patients with relapsed/refractory AL amyloidosis treated with ixazomib-dexamethasone versus physician's choice. Am J Hematol. 2023 May;98(5):720-729. Epub 2023 Feb 14. link to original article PubMed

Melphalan & Dexamethasone

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Dispenzieri et al. 2021 (Tourmaline-AL1)	2012-2018	Phase 3 (C)	Ixazomib & Dexamethasone	Did not meet primary endpoint of HRR

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) 0.22 mg/kg PO once per day on days 1 to 4

Glucocorticoid therapy

Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4

28-day cycles

References

Tourmaline-AL1: Dispenzieri A, Kastritis E, Wechalekar AD, Schönland SO, Kim K, Sanchorawala V, Landau HJ, Kwok F, Suzuki K, Comenzo RL, Berg D, Liu G, Kumar A, Faller DV, Merlini G. A randomized phase 3 study of ixazomib-dexamethasone versus physician's choice in relapsed or refractory AL amyloidosis. Leukemia. 2022 Jan;36(1):225-235. Epub 2021 Jun 24. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01659658
1. HRQoL analysis: Sanchorawala V, Wechalekar AD, Kim K, Schönland SO, Landau HJ, Kwok F, Suzuki K, Dispenzieri A, Merlini G, Comenzo RL, Cherepanov D, Hayden VC, Kumar A, Labotka R, Faller DV, Kastritis E. Quality of life and symptoms among patients with relapsed/refractory AL amyloidosis treated with ixazomib-dexamethasone versus physician's choice. Am J Hematol. 2023 May;98(5):720-729. Epub 2023 Feb 14. link to original article PubMed

Pomalidomide & Dexamethasone (Pd)

Pd: Pomalidomide & low-dose dexamethasone

Regimen variant #1

Study	Dates of enrollment	Evidence
Palladini et al. 2017 (AC-007-IT)	2012-2013	Phase 2

Targeted therapy

Pomalidomide (Pomalyst) 4 mg PO once per day on days 1 to 28

Glucocorticoid therapy

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

28-day cycles

Regimen variant #2

Study	Dates of enrollment	Evidence
Sanchorawala et al. 2016 (PO-AMYL-PI-0024)	2012-2015	Phase 1/2, fewer than 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

Glucocorticoid therapy

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

28-day cycles

Regimen variant #3

Study	Dates of enrollment	Evidence
Dispenzieri et al. 2012 (MC0789_AL)	2008-2010	Phase 2

Targeted therapy

Pomalidomide (Pomalyst) 2 mg PO once per day on days 1 to 28

Glucocorticoid therapy

Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22

Supportive therapy

Thromboprophylaxis: Aspirin 325 mg PO once per day on days 1 to 28

28-day cycles

Dose and schedule modifications

See Dispenzieri et al. 2012 for Pomalidomide (Pomalyst) dose escalations and reductions

References

MC0789_AL: 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 dosing details in manuscript link to PMC article PubMed NCT00558896
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 dosing details in manuscript PubMed NCT01570387
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 dosing details in manuscript PubMed NCT01510613

Lenalidomide & Dexamethasone (Rd)

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

Regimen variant #1, weekly dexamethasone

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Palladini et al. 2011	2007-2009	Phase 2
Dispenzieri et al. 2021 (Tourmaline-AL1)	2012-2018	Phase 3 (C)	Ixazomib & Dexamethasone	Did not meet primary endpoint of HRR

Targeted therapy

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

Glucocorticoid therapy

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

Supportive therapy

Thromboprophylaxis: Aspirin 100 mg PO once per day on days 1 to 28
Omeprazole (Prilosec) 20 mg PO once per day on days 1 to 28

28-day cycles

Regimen variant #2, pulsed dexamethasone

Study	Dates of enrollment	Evidence
Sanchorwala et al. 2006	2004-2006	Phase 2

Prior treatment criteria

Treatment failure after lenalidomide x 3

Targeted therapy

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

Glucocorticoid therapy

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 therapy

Thromboprophylaxis: Aspirin 81 or 325 mg PO once per day on days 1 to 28
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 dosing details in manuscript 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. Epub 2011 Apr 30. link to original article contains dosing details in manuscript PubMed
Tourmaline-AL1: Dispenzieri A, Kastritis E, Wechalekar AD, Schönland SO, Kim K, Sanchorawala V, Landau HJ, Kwok F, Suzuki K, Comenzo RL, Berg D, Liu G, Kumar A, Faller DV, Merlini G. A randomized phase 3 study of ixazomib-dexamethasone versus physician's choice in relapsed or refractory AL amyloidosis. Leukemia. 2022 Jan;36(1):225-235. Epub 2021 Jun 24. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01659658
1. HRQoL analysis: Sanchorawala V, Wechalekar AD, Kim K, Schönland SO, Landau HJ, Kwok F, Suzuki K, Dispenzieri A, Merlini G, Comenzo RL, Cherepanov D, Hayden VC, Kumar A, Labotka R, Faller DV, Kastritis E. Quality of life and symptoms among patients with relapsed/refractory AL amyloidosis treated with ixazomib-dexamethasone versus physician's choice. Am J Hematol. 2023 May;98(5):720-729. Epub 2023 Feb 14. link to original article PubMed

Lenalidomide & Dexamethasone (RD)

RD: Revlimid (Lenalidomide) & high-dose Dexamethasone

Regimen

Study	Dates of enrollment	Evidence
Dispenzieri et al. 2006 (MC0484)	2004-2005	Phase 2

Prior treatment criteria

Treatment failure after lenalidomide x 3

Targeted therapy

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

Glucocorticoid therapy

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

MC0484: 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 dosing details in manuscript PubMed

Thalidomide & Dexamethasone (TD)

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Dispenzieri et al. 2021 (Tourmaline-AL1)	2012-2018	Phase 3 (C)	Ixazomib & Dexamethasone	Did not meet primary endpoint of HRR

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

Targeted therapy

Thalidomide (Thalomid) 50 mg PO once per day on days 1 to 28

Glucocorticoid therapy

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

28-day cycles

Dose and schedule modifications

Thalidomide dose is increased to 200 mg PO once per day as tolerated

References

Tourmaline-AL1: Dispenzieri A, Kastritis E, Wechalekar AD, Schönland SO, Kim K, Sanchorawala V, Landau HJ, Kwok F, Suzuki K, Comenzo RL, Berg D, Liu G, Kumar A, Faller DV, Merlini G. A randomized phase 3 study of ixazomib-dexamethasone versus physician's choice in relapsed or refractory AL amyloidosis. Leukemia. 2022 Jan;36(1):225-235. Epub 2021 Jun 24. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01659658
1. HRQoL analysis: Sanchorawala V, Wechalekar AD, Kim K, Schönland SO, Landau HJ, Kwok F, Suzuki K, Dispenzieri A, Merlini G, Comenzo RL, Cherepanov D, Hayden VC, Kumar A, Labotka R, Faller DV, Kastritis E. Quality of life and symptoms among patients with relapsed/refractory AL amyloidosis treated with ixazomib-dexamethasone versus physician's choice. Am J Hematol. 2023 May;98(5):720-729. Epub 2023 Feb 14. link to original article PubMed

Light-chain (AL) amyloidosis

Guidelines

BSH

EMN

NCCN

First-line therapy (including transplant ineligible)

CRd

Regimen variant #1, "LDC"

Chemotherapy

Glucocorticoid therapy

Targeted therapy

Supportive therapy

Subsequent treatment

Dose and schedule modifications

Regimen variant #2, "CRd"

Chemotherapy

Glucocorticoid therapy

Targeted therapy

Supportive therapy

Regimen variant #3, "RdC"

Chemotherapy

Glucocorticoid therapy

Targeted therapy

Supportive therapy

References

CTD

Regimen variant #1

Chemotherapy

Glucocorticoid therapy

Targeted therapy

Supportive therapy

Regimen variant #2, risk attenuated regimen

Eligibility criteria

Chemotherapy

Glucocorticoid therapy

Targeted therapy

Supportive therapy

References

Dara-CyBorD

Synopsis

Regimen

Targeted therapy

Chemotherapy

Glucocorticoid therapy

References

Doxycycline-CyBorD

Regimen

Targeted therapy

Chemotherapy

Glucocorticoid therapy

References

Lenalidomide monotherapy

Regimen variant #1, 15 mg dosing

Targeted therapy

Supportive therapy

Subsequent treatment

Regimen variant #2, 25 mg dosing

Targeted therapy

Subsequent treatment

References

Melphalan & Dexamethasone

Regimen variant #1, BSA-based melphalan

Chemotherapy

Glucocorticoid therapy

Supportive therapy

Regimen variant #2, weight-based melphalan

Chemotherapy

Glucocorticoid therapy

Supportive therapy

References

MRD

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

Chemotherapy

Glucocorticoid therapy

Targeted therapy

Supportive therapy

Regimen variant #2

Chemotherapy

Glucocorticoid therapy

Targeted therapy

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