Light-chain (AL) amyloidosis
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25 regimens on this page
48 variants on this page
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Untreated (including transplant ineligible)
Bortezomib & Dexamethasone
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Regimen
| Study | Evidence | Comparator |
| Huang et al. 2014 | Randomized Phase II | High-dose melphalan -> auto SCT |
| Sanchorawala et al. 2015 | Phase II |
Details of dosing not available in the Sanchorawala et al. 2015 abstract.
Chemotherapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Dexamethasone (Decadron) 40 mg PO once per day on days 1, 4, 8, 11
21-day cycle for 2 cycles
Treatment in Huang et al. 2014 followed by high-dose melphalan -> autologous stem cell transplant. Treatment in Sanchorawala et al. 2015 followed by bortezomib & high-dose melphalan -> autologous stem cell transplant.
References
- Huang X, Wang Q, Chen W, Zeng C, Chen Z, Gong D, Zhang H, Liu Z. Induction therapy with bortezomib and dexamethasone followed by autologous stem cell transplantation versus autologous stem cell transplantation alone in the treatment of renal AL amyloidosis: a randomized controlled trial. BMC Med. 2014 Jan 6;12:2. link to original article contains verified protocol PubMed
- 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 PubMed
CRd, LDC, RdC
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CRd: Cyclophosphamide, Revlimid (Lenalidomide), low-dose dexamethasone
LDC: Lenalidomide, Dexamethasone, Cyclophosphamide
RdC: Revlimid (Lenalidomide), low-dose dexamethasone, Cyclophosphamide
Regimen #1, "LDC"
| Study | Evidence |
| Cibeira et al. 2015 | Phase II |
Chemotherapy
- Lenalidomide (Revlimid) as follows:
- Normal eGFR: 15 mg PO once per day on days 1 to 21
- GFR >30 but <50: 10 mg PO once per day on days 1 to 21
- GFR <30: 5 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) as follows:
- Cycles 1 to 6: 20 mg PO once per day on days 1 to 4, 9 to 12
- Cycles 7 to 12: 20 mg PO once per day on days 1 to 4
- Cardiac stage III (this is not defined): upfront modification "allowed" but not defined
- 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
Supportive medications
- Aspirin 100 mg PO once per day, or Low molecular weight heparin
28-day cycle for 12 cycles
Patients without progression who were tolerating therapy proceeded to lenalidomide & dexamethasone maintenance.
Regimen #2, "CRd"
| Study | Evidence |
| Kumar et al. 2012 | Phase II |
Chemotherapy
- Cyclophosphamide (Cytoxan) 500 mg PO once per day on days 1, 8, 15
- Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22
Supportive medications
- Aspirin 81, 100, or 325 mg PO once per day for thromboprophylaxis
- 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)
- "Routine antibiotic, antiviral, or antifungal prophylaxis was not mandated and left to the discretion of the treating physician."
28-day cycle for up to 2 years
Regimen #3, "RdC"
| Study | Evidence |
| Kastritis et al. 2012 | Phase I/II |
This was the highest dose level tested in Kastritis et al. 2012, which had no dose-limiting toxicities.
Chemotherapy
- Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4
- Cyclophosphamide (Cytoxan) 100 mg PO once per day on days 1 to 10
Supportive medications
- Aspirin 100 mg PO once daily for thromboprophylaxis
- Proton pump inhibitor
- Trimethoprim-sulfamethoxazole (Bactrim), dose and schedule not listed
- Valacyclovir (Valtrex), dose and schedule not listed
28-day cycle for 12 cycles
References
- Kumar SK, Hayman SR, Buadi FK, Roy V, Lacy MQ, Gertz MA, Allred J, Laumann KM, Bergsagel LP, Dingli D, Mikhael JR, Reeder CB, Stewart AK, Zeldenrust SR, Greipp PR, Lust JA, Fonseca R, Russell SJ, Rajkumar SV, Dispenzieri A. Lenalidomide, cyclophosphamide, and dexamethasone (CRd) for light-chain amyloidosis: long-term results from a phase 2 trial. Blood. 2012 May 24;119(21):4860-7. Epub 2012 Apr 13. link to original article contains verified protocol PubMed
- Kastritis E, Terpos E, Roussou M, Gavriatopoulou M, Pamboukas C, Boletis I, Marinaki S, Apostolou T, Nikitas N, Gkortzolidis G, Michalis E, Delimpasi S, Dimopoulos MA. A phase 1/2 study of lenalidomide with low-dose oral cyclophosphamide and low-dose dexamethasone (RdC) in AL amyloidosis. Blood. 2012 Jun 7;119(23):5384-90. Epub 2012 Apr 18. link to original article contains verified protocol PubMed
- Cibeira MT, Oriol A, Lahuerta JJ, Mateos MV, de la Rubia J, Hernández MT, Granell M, Fernández de Larrea C, San Miguel JF, Bladé J; PETHEMA cooperative study group. A phase II trial of lenalidomide, dexamethasone and cyclophosphamide for newly diagnosed patients with systemic immunoglobulin light chain amyloidosis. Br J Haematol. 2015 Sep;170(6):804-13. Epub 2015 May 14. link to original article contains verified protocol PubMed
CTD
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CTD: Cyclophosphamide, Thalidomide, Dexamethasone
Regimen #1
| Study | Evidence |
| Wechalekar et al. 2007 | Phase II |
Chemotherapy
- Cyclophosphamide (Cytoxan) 500 mg PO once per week
- Thalidomide (Thalomid) 100 mg PO once per day on days 1 to 21, then increased to 200 mg PO once per day if well tolerated after 4 weeks
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 9 to 12
Supportive medications
- "Antimicrobial and thromboprophylaxis were given according to local protocol"; no routine thromboprophylaxis
21-day cycles, "given until a stable clonal response was achieved on consecutive samples at least 4 weeks apart" or until confirmed lack of response
Regimen #2, risk attenuated regimen
| Study | Evidence |
| Wechalekar et al. 2007 | Phase II |
For elderly patients (age >70 years), NYHA heart failure >class II, and those with significant fluid overload.
Chemotherapy
- Cyclophosphamide (Cytoxan) 500 mg PO once per day on days 1, 8, 15
- Thalidomide (Thalomid) 50 mg PO once per day on days 1 to 28, increased by 50 mg every 4 weeks as tolerated to a maximum dose of 200 mg PO once per day
- Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4, 15 to 18
Supportive medications
- "Antimicrobial and thromboprophylaxis were given according to local protocol"; no routine thromboprophylaxis
28-day cycles, "given until a stable clonal response was achieved on consecutive samples at least 4 weeks apart" or until confirmed lack of response
References
- Wechalekar AD, Goodman HJ, Lachmann HJ, Offer M, Hawkins PN, Gillmore JD. Safety and efficacy of risk-adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL amyloidosis. Blood. 2007 Jan 15;109(2):457-64. Epub 2006 Sep 21. link to original article contains verified protocol PubMed
CyBorD
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CyBorD: Cyclophosphamide, Bortezomib, Dexamethasone
Regimen
| Study | Evidence |
| Mikhael et al. 2012 | Phase II, <20 pts |
Chemotherapy
- Cyclophosphamide (Cytoxan) 300 mg/m2 PO once per week
- Bortezomib (Velcade) 1.5 mg/m2 (route not specified) once per week OR 1.3 mg/m2 on days 1, 4, 8, 11
- Dexamethasone (Decadron) 40 mg (route not specified) once per week
Supportive medications
- "Antiviral prophylaxis"
28-day cycle for 2 to 6 cycles
References
- Mikhael JR, Schuster SR, Jimenez-Zepeda VH, Bello N, Spong J, Reeder CB, Stewart AK, Bergsagel PL, Fonseca R. Cyclophosphamide-bortezomib-dexamethasone (CyBorD) produces rapid and complete hematologic response in patients with AL amyloidosis. Blood. 2012 May 10;119(19):4391-4. Epub 2012 Feb 13. link to original article contains verified protocol 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 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
Lenalidomide (Revlimid)
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Regimen #1, 15 mg dosing
| Study | Evidence |
| Sanchorwala et al. 2006 | Phase II |
The trial used an initial dose of lenalidomide of 25 mg PO once per day, but it was reduced to 15 mg because 25 mg was poorly tolerated.
Chemotherapy
- Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 21
Supportive medications
- Aspirin 81 or 325 mg (physician discretion) PO once per day as prophylaxis
28-day cycles
If no response after 3 cycles of therapy, then patients were escalated to lenalidomide & dexamethasone. Otherwise, treatment continued until progression of disease or unacceptable toxicity.
Regimen #2, 25 mg dosing
| Study | Evidence |
| Dispenzieri et al. 2006 | Phase II |
Chemotherapy
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
28-day cycles
If no response after 3 cycles of therapy, then patients were escalated to lenalidomide & dexamethasone. Otherwise, treatment continued with a target of 12 cycles, total.
References
- Sanchorawala V, Wright DG, Rosenzweig M, Finn KT, Fennessey S, Zeldis JB, Skinner M, Seldin DC. Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial. Blood. 2007 Jan 15;109(2):492-6. Epub 2006 Sep 7. link to original article contains verified protocol PubMed
- Update: Sanchorawala V, Finn KT, Fennessey S, Shelton A, Doros G, Zeldis JB, Seldin DC. Durable hematologic complete responses can be achieved with lenalidomide in AL amyloidosis. Blood. 2010 Sep 16;116(11):1990-1. link to original article PubMed
- Dispenzieri A, Lacy MQ, Zeldenrust SR, Hayman SR, Kumar SK, Geyer SM, Lust JA, Allred JB, Witzig TE, Rajkumar SV, Greipp PR, Russell SJ, Kabat B, Gertz MA. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood. 2007 Jan 15;109(2):465-70. Epub 2006 Sep 28. link to original article contains verified protocol PubMed
Melphalan & Dexamethasone
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Regimen #1
| Study | Evidence | Comparator |
| Jaccard et al. 2007 | Phase III | High-dose melphalan -> autologous stem cell transplant |
Chemotherapy
- Melphalan (Alkeran) 10 mg/m2 PO once per day on days 1 to 4
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
Supportive medications
- Proton pump inhibitor
- Trimethoprim/Sulfamethoxazole (Bactrim DS) three times per week
1-month cycle for up to 18 cycles
Patients achieving complete hematologic remission could stop treatment after 12 cycles.
Regimen #2
| Study | Evidence |
| Palladini et al. 2003 | Phase II |
Chemotherapy
- Melphalan (Alkeran) 0.22 mg/kg PO once per day on days 1 to 4
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
Supportive medications
- Omeprazole (Prilosec) 20 mg PO once per day on days 1 to 10
- Ciprofloxacin (Cipro) 250 mg PO BID on days 1 to 10
- Itraconazole (Sporanox) 100 mg PO once per day on days 1 to 10
28-day cycle for up to 9 cycles
References
- Palladini G, Perfetti V, Obici L, Caccialanza R, Semino A, Adami F, Cavallero G, Rustichelli R, Virga G, Merlini G. Association of melphalan and high-dose dexamethasone is effective and well tolerated in patients with AL (primary) amyloidosis who are ineligible for stem cell transplantation. Blood. 2004 Apr 15;103(8):2936-8. Epub 2003 Dec 18. link to original article contains protocol PubMed
- 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 PubMed
- Jaccard A, Moreau P, Leblond V, Leleu X, Benboubker L, Hermine O, Recher C, Asli B, Lioure B, Royer B, Jardin F, Bridoux F, Grosbois B, Jaubert J, Piette JC, Ronco P, Quet F, Cogne M, Fermand JP; Myélome Autogreffe (MAG) and Intergroupe Francophone du Myélome (IFM) Intergroup. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med. 2007 Sep 13;357(11):1083-93. link to original article contains verified protocol PubMed
MRD
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MRD: Melphalan, Revlimid (Lenalidomide), Dexamethasone
Regimen #1
| Study | Evidence |
| Sanchorwala et al. 2012 | Phase II, <20 pts |
Sanchorawala et al. 2012 did not outright specify oral routes for melphalan and dexamethasone, but this is assumed based on how the paper discussed existing oral melphalan and dexamethasone regimens.
Chemotherapy
- Melphalan (Alkeran) 5 mg/m2 PO once per day on days 1 to 4
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 40 mg PO once per week
Supportive medications
- Aspirin 325 mg PO once per day to decrease risk of Lenalidomide (Revlimid)-associated venous thromboembolism (VTE)
- Proton pump inhibitor to decrease risk of gastritis from Dexamethasone (Decadron)
28-day cycle for 12 cycles, until progression of disease, or unacceptable toxicity
Regimen #2
| Study | Evidence |
| Moreau et al. 2010 | Phase I/II |
This is the MTD dosing.
Chemotherapy
- Melphalan (Alkeran) 0.18 mg/kg PO once per day on days 1 to 4
- Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
Supportive medications
28-day cycle for up to 9 cycles
References
- Moreau P, Jaccard A, Benboubker L, Royer B, Leleu X, Bridoux F, Salles G, Leblond V, Roussel M, Alakl M, Hermine O, Planche L, Harousseau JL, Fermand JP. Lenalidomide in combination with melphalan and dexamethasone in patients with newly diagnosed AL amyloidosis: a multicenter phase 1/2 dose-escalation study. Blood. 2010 Dec 2;116(23):4777-82. Epub 2010 Aug 19. link to original article contains verified protocol PubMed
- Sanchorawala V, Patel JM, Sloan JM, Shelton AC, Zeldis JB, Seldin DC. Melphalan, lenalidomide and dexamethasone for the treatment of immunoglobulin light chain amyloidosis: results of a phase II trial. Haematologica. 2013 May;98(5):789-92. Epub 2012 Nov 9. link to original article contains verified protocol PubMed
VMD
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VMD: Velcade (Bortezomib), Melphalan, Dexamethasone
Regimen
| Study | Evidence |
| Zonder et al. 2009 | Phase II |
Chemotherapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 8, 15, 22, given first
- Patients with peripheral neuropathy at baseline received 1.0 mg/m2 IV once per day on days 1, 8, 15, 22
- Melphalan (Alkeran) 9 mg/m2 PO once per day on days 1 to 4, given last
- Patients with serum creatinine >2.5 mg/dL received 6 mg/m2 PO once per day on days 1 to 4
- Dexamethasone (Decadron) 40 mg PO/IV once per day on days 1, 8, 15, 22, given second
- Patients at least 70 years of age, with peripheral edema or congestive heart failure (CHF) received 20 mg PO/IV 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
Consolidation and/or maintenance after upfront therapy
Bortezomib & Dexamethasone
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Regimen
| Study | Evidence |
| Landau et al. 2012 | Phase II |
Treatment preceded by high-dose melphalan -> autologous stem cell transplant. Details of dosing not available in the abstract.
Chemotherapy
References
- Landau H, Hassoun H, Rosenzweig MA, Maurer M, Liu J, Flombaum C, Bello C, Hoover E, Riedel E, Giralt S, Comenzo RL. Bortezomib and dexamethasone consolidation following risk-adapted melphalan and stem cell transplantation for patients with newly diagnosed light-chain amyloidosis. Leukemia. 2013 Apr;27(4):823-8. Epub 2012 Sep 27. link to original article contains protocol PubMed
Bortezomib & Melphalan -> autologous stem cell transplant
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Regimen
| Study | Evidence |
| Sanchorawala et al. 2015 | Phase II |
Treatment preceded by bortezomib & dexamethasone x 2. Details of dosing not available in the abstract.
Chemotherapy
References
- 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 PubMed
Lenalidomide & Dexamethasone
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Regimen
| Study | Evidence |
| Cibeira et al. 2015 | Phase II |
Treatment preceded by LDC x 12.
Chemotherapy
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4
Supportive medications
- Aspirin 100 mg PO once per day or Low molecular weight heparin
28-day cycle for 3 years
References
- 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 cooperative study group. A phase II trial of lenalidomide, dexamethasone and cyclophosphamide for newly diagnosed patients with systemic immunoglobulin light chain amyloidosis. Br J Haematol. 2015 Sep;170(6):804-13. Epub 2015 May 14. link to original article contains verified protocol PubMed
Melphalan -> autologous stem cell transplant
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To be completed. See details about preparative regimens.
References
- 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; Myélome Autogreffe (MAG) and Intergroupe Francophone du Myélome (IFM) Intergroup. 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 PubMed
- Landau H, Hassoun H, Rosenzweig MA, Maurer M, Liu J, Flombaum C, Bello C, Hoover E, Riedel E, Giralt S, Comenzo RL. Bortezomib and dexamethasone consolidation following risk-adapted melphalan and stem cell transplantation for patients with newly diagnosed light-chain amyloidosis. Leukemia. 2013 Apr;27(4):823-8. Epub 2012 Sep 27. link to original article contains protocol PubMed
- 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 PubMed
Relapsed/refractory
Bortezomib (Velcade)
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Regimen #1, twice per week
| Study | Evidence |
| Reece et al. 2011 (CAN2007) | Phase II |
Chemotherapy
- 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 #2, weekly schedule
| Study | Evidence |
| Reece et al. 2011 (CAN2007) | Phase II |
Chemotherapy
- 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
- Reece DE, Hegenbart U, Sanchorawala V, Merlini G, Palladini G, Bladé J, Fermand JP, Hassoun H, Heffner L, Vescio RA, Liu K, Enny C, Esseltine DL, van de Velde H, Cakana A, Comenzo RL. Efficacy and safety of once-weekly and twice-weekly bortezomib in patients with relapsed systemic AL amyloidosis: results of a phase 1/2 study. Blood. 2011 Jul 28;118(4):865-73. Epub 2011 May 11. link to original article contains verified protocol PubMed
- Update: Reece DE, Hegenbart U, Sanchorawala V, Merlini G, Palladini G, Bladé J, Fermand JP, Hassoun H, Heffner L, Kukreti V, Vescio RA, Pei L, Enny C, Esseltine DL, van de Velde H, Cakana A, Comenzo RL. Long-term follow-up from a phase 1/2 study of single-agent bortezomib in relapsed systemic AL amyloidosis. Blood. 2014 Oct 16;124(16):2498-506. Epub 2014 Sep 8. link to original article contains verified protocol PubMed
CRD
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CRD: Cyclophosphamide, Revlimid (Lenalidomide), Dexamethasone
Regimen
| Study | Evidence |
| Kumar et al. 2012 | Phase II |
| Palladini et al. 2012 | Phase II |
Chemotherapy
- Cyclophosphamide (Cytoxan) 500 mg PO once per day on days 1, 8, 15
- Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22
- In Palladini et al. 2013 only, patients who retained over 3% body weight despite "optimal diuretic use" received Dexamethasone (Decadron) 20 mg PO once per week
Supportive medications
(varies depending on reference)
- Aspirin 81, 100, or 325 mg PO once per day for thromboprophylaxis
- In Kumar et al. 2012, patients with previous thrombotic histories or who were considered to be higher thrombotic risks were recommended to receive low molecular weight heparin or Warfarin (Coumadin)
- Kumar et al. 2012: "Routine antibiotic, antiviral, or antifungal prophylaxis was not mandated and left to the discretion of the treating physician."
28-day cycle for up to 9 cycles or 2 years, depending on reference
References
- Kumar SK, Hayman SR, Buadi FK, Roy V, Lacy MQ, Gertz MA, Allred J, Laumann KM, Bergsagel LP, Dingli D, Mikhael JR, Reeder CB, Stewart AK, Zeldenrust SR, Greipp PR, Lust JA, Fonseca R, Russell SJ, Rajkumar SV, Dispenzieri A. Lenalidomide, cyclophosphamide, and dexamethasone (CRd) for light-chain amyloidosis: long-term results from a phase 2 trial. Blood. 2012 May 24;119(21):4860-7. Epub 2012 Apr 13. link to original article contains verified protocol PubMed
- Palladini G, Russo P, Milani P, Foli A, Lavatelli F, Nuvolone M, Perlini S, Merlini G. A phase II trial of cyclophosphamide, lenalidomide and dexamethasone in previously treated patients with AL amyloidosis. Haematologica. 2013 Mar;98(3):433-6. Epub 2012 Sep 14. link to original article contains verified protocol PubMed
CTD
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CTD: Cyclophosphamide, Thalidomide, Dexamethasone
Regimen #1
| Study | Evidence |
| Wechalekar et al. 2007 | Phase II |
Chemotherapy
- Cyclophosphamide (Cytoxan) 500 mg PO once per week
- Thalidomide (Thalomid) 100 mg PO once per day on days 1 to 21, then increased to 200 mg PO once per day on days 1 to 21 if well tolerated after 4 weeks
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 9 to 12
Supportive medications
- "Antimicrobial and thromboprophylaxis were given according to local protocol"; no routine thromboprophylaxis
21-day cycles, "given until a stable clonal response was achieved on consecutive samples at least 4 weeks apart" or until confirmed lack of response
Regimen #2, risk attenuated regimen
| Study | Evidence |
| Wechalekar et al. 2007 | Phase II |
For elderly patients (age >70 years), NYHA heart failure >class II, and those with significant fluid overload.
Chemotherapy
- Cyclophosphamide (Cytoxan) 500 mg PO once per day on days 1, 8, 15
- Thalidomide (Thalomid) 50 mg PO once per day on days 1 to 28, increased by 50 mg every 4 weeks as tolerated to a maximum dose of 200 mg PO once per day
- Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4, 15 to 18
Supportive medications
- "Antimicrobial and thromboprophylaxis were given according to local protocol"; no routine thromboprophylaxis
28-day cycles, "given until a stable clonal response was achieved on consecutive samples at least 4 weeks apart" or until confirmed lack of response
References
- Wechalekar AD, Goodman HJ, Lachmann HJ, Offer M, Hawkins PN, Gillmore JD. Safety and efficacy of risk-adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL amyloidosis. Blood. 2007 Jan 15;109(2):457-64. Epub 2006 Sep 21. link to original article contains verified protocol PubMed
Lenalidomide & Dexamethasone
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Regimen #1
| Study | Evidence |
| Sanchorwala et al. 2006 | Phase II |
Preceded by treatment failure after lenalidomide x 3 cycles.
Chemotherapy
- Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 10 to 20 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20, given every other cycle
Supportive medications
- Aspirin 81 or 325 mg (physician discretion) PO once per day as thromboprophylaxis
- Proton pump inhibitor
28-day cycles, given until progression of disease or unacceptable toxicity
Regimen #2
| Study | Evidence |
| Dispenzieri et al. 2006 | Phase II |
Preceded by treatment failure after lenalidomide x 3 cycles.
Chemotherapy
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 15 to 18
28-day cycle with target 12 total cycles, could continue if response observed
References
- Sanchorawala V, Wright DG, Rosenzweig M, Finn KT, Fennessey S, Zeldis JB, Skinner M, Seldin DC. Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial. Blood. 2007 Jan 15;109(2):492-6. Epub 2006 Sep 7. link to original article contains verified protocol PubMed
- Dispenzieri A, Lacy MQ, Zeldenrust SR, Hayman SR, Kumar SK, Geyer SM, Lust JA, Allred JB, Witzig TE, Rajkumar SV, Greipp PR, Russell SJ, Kabat B, Gertz MA. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood. 2007 Jan 15;109(2):465-70. Epub 2006 Sep 28. link to original article contains verified protocol PubMed
Pomalidomide & Dexamethasone
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Regimen #1
| Study | Evidence |
| Sanchorawala et al. 2016 | Phase I/II, <20 pts |
Note: although the trial enrolled 27 patients, only 18 were treated at the MTD reproduced here:
Chemotherapy
- Pomalidomide (Pomalyst) 4 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 20 mg PO once per week
28-day cycles
Regimen #2
| Study | Evidence |
| Dispenzieri et al. 2012 | Phase II |
Chemotherapy
- Pomalidomide (Pomalyst) 2 mg PO once per day on days 1 to 28
- See Dispenzieri et al. 2012 for dose escalations and reductions
- Dexamethasone (Decadron) 40 mg PO once per week
Supportive medications
- Aspirin 325 mg PO once per day for thromboprophylaxis
28-day cycles, given until progression of disease
References
- Dispenzieri A, Buadi F, Laumann K, LaPlant B, Hayman SR, Kumar SK, Dingli D, Zeldenrust SR, Mikhael JR, Hall R, Rajkumar SV, Reeder C, Fonseca R, Bergsagel PL, Stewart AK, Roy V, Witzig TE, Lust JA, Russell SJ, Gertz MA, Lacy MQ. Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. Blood. 2012 Jun 7;119(23):5397-404. Epub 2012 Apr 4. link to original article contains verified protocol PubMed
- Sanchorawala V, Shelton AC, Lo S, Varga C, Sloan JM, Seldin DC. Pomalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 1 and 2 trial. Blood. 2016 Aug 25;128(8):1059-62. Epub 2016 Jul 5. link to original article contains verified protocol PubMed
RdC
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RdC: Revlimid (Lenalidomide), dexamethasone, Cyclophosphamide
Regimen
| Study | Evidence |
| Kastritis et al. 2012 | Phase II |
This was the highest dose level tested, which had no dose-limiting toxicities.
Chemotherapy
- Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4
- Cyclophosphamide (Cytoxan) 100 mg PO once per day on days 1 to 10
Supportive medications
- Aspirin 100 mg PO once per day for thromboprophylaxis
- 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
- Kastritis E, Terpos E, Roussou M, Gavriatopoulou M, Pamboukas C, Boletis I, Marinaki S, Apostolou T, Nikitas N, Gkortzolidis G, Michalis E, Delimpasi S, Dimopoulos MA. A phase 1/2 study of lenalidomide with low-dose oral cyclophosphamide and low-dose dexamethasone (RdC) in AL amyloidosis. Blood. 2012 Jun 7;119(23):5384-90. Epub 2012 Apr 18. link to original article contains verified protocol PubMed