Light-chain (AL) amyloidosis

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Last updated on 2024-07-23:28 regimens on this page
50 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 EuroPMC
==EMN==
*2018: Gavriatopoulou et al. European myeloma network recommendations on diagnosis and management of patients with rare plasma cell dyscrasias EuroPMC
==mSMART==
*2021: Muchtar et al. Treatment of AL Amyloidosis: Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Statement 2020 Update EuroPMC
**2015: Dispenzieri et al. Treatment of Immunoglobulin Light Chain Amyloidosis: Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Statement EuroPMC
==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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==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 ).
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 ). 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 ), 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 ). The trial results demonstrated improved hematologic response rates, organ response rates, and progression-free survival for Dara-VCd (Kastritis et al., 2021 ), 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 	Higher 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT03201965
##HRQoL analysis: Sanchorawala V, Palladini G, Minnema MC, Jaccard A, Lee HC, Gibbs S, Mollee P, Venner C, Lu J, Schönland S, Gatt M, Suzuki K, Kim K, Cibeira MT, Beksac M, Libby E, Valent J, Hungria V, Wong SW, Rosenzweig M, Bumma N, Chauveau D, Gries KS, Fastenau J, Tran NP, Qin X, Vasey SY, Weiss BM, Vermeulen J, Ho KF, Merlini G, Comenzo RL, Kastritis E, Wechalekar AD. Health-related quality of life in patients with light chain amyloidosis treated with bortezomib, cyclophosphamide, and dexamethasone ± daratumumab: Results from the ANDROMEDA study. Am J Hematol. 2022 Jun 1;97(6):719-730. Epub 2022 Mar 30. link to original article EuroPMC
==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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC
## 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==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 longer 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 	Shorter 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 dosing details in manuscript have been reviewed by our editors EuroPMC
## 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 EuroPMC
## 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC 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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC 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)	2010-01 to 2013-08 	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====
*Proton pump inhibitor
*Antiviral medication
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 longer 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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NTR3220
==VDC==
VDC: Velcade (Bortezomib), Dexamethasone, Cyclophosphamide
CyBorD: Cyclophosphamide, Bortezomib, Dexamethasone
===Regimen variant #1, 300/1.3/40, uncapped cyclophosphamide===
Study 	Dates of enrollment	Evidence
Mikhael et al. 2012	2007-2010 	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 	Lower 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 	Dates of enrollment	Evidence
Mikhael et al. 2012	2007-2010 	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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
# 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 EuroPMC
# 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 EuroPMC
#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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT03201965
##HRQoL analysis: Sanchorawala V, Palladini G, Minnema MC, Jaccard A, Lee HC, Gibbs S, Mollee P, Venner C, Lu J, Schönland S, Gatt M, Suzuki K, Kim K, Cibeira MT, Beksac M, Libby E, Valent J, Hungria V, Wong SW, Rosenzweig M, Bumma N, Chauveau D, Gries KS, Fastenau J, Tran NP, Qin X, Vasey SY, Weiss BM, Vermeulen J, Ho KF, Merlini G, Comenzo RL, Kastritis E, Wechalekar AD. Health-related quality of life in patients with light chain amyloidosis treated with bortezomib, cyclophosphamide, and dexamethasone ± daratumumab: Results from the ANDROMEDA study. Am J Hematol. 2022 Jun 1;97(6):719-730. Epub 2022 Mar 30. link to original article EuroPMC
# 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 EuroPMC 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 link to PMC article EuroPMC 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 	Longer 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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)	2010-01 to 2013-08 	Phase 2 	HRR: 77%
====Preceding treatment====
*Bortezomib & Dexamethasone induction x 2 
===Regimen variant #2, HDM 200 mg/m2===
Study 	Dates of enrollment	Evidence	Efficacy
Sanchorawala et al. 2015 (X05292)	2010-01 to 2013-08 	Phase 2 	HRR: 77%
====Preceding treatment====
*Bortezomib & Dexamethasone induction x 2 
===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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 shorter 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 shorter 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC
=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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00298766
## 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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
==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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT01659658
##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 EuroPMC
==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 	Dates of enrollment	Evidence
Kaufman et al. 2017	2016-01 to 2016-12 	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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT01659658
##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 EuroPMC
==Ixazomib monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence
Sanchorawala et al. 2017 (C16007)	2012 to not reported	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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01318902
==Ixazomib & Dexamethasone==
===Regimen===
Study 	Dates of enrollment 	Evidence
Sanchorawala et al. 2017 (C16007)	2012 to not reported	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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC 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 EuroPMC NCT01659658
##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 EuroPMC
==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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT01659658
##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 EuroPMC
==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 (MC0789AL)	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===
# MC0789AL: 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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
#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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT01659658
##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 EuroPMC
==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 dosing details in manuscript have been reviewed by our editors EuroPMC
==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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT01659658
##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 EuroPMC
Category:Light-chain (AL) amyloidosis regimens
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Category:Plasma cell dyscrasias