Light-chain (AL) amyloidosis

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25 regimens on this page
48 variants on this page


Untreated (including transplant ineligible)

CRd, LDC

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CRd: Cyclophosphamide, Revlimid (Lenalidomide), dexamethasone
LDC: Lenalidomide, Dexamethasone, Cyclophosphamide

Regimen #1, LDC

Study Evidence
Cibeira et al. 2015 Phase II

Supportive medications:

OR

Dose reductions:

28-day cycle x 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

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 cycles x up to 2 years

References

  1. 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
  2. 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

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.

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

  1. 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

Phase II, <20 patients reported

Supportive medications:

  • "Antiviral prophylaxis"

28-day cycles x 2 to 6 cycles

References

  1. 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
  2. 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.

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

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

  1. 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
  2. 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

Phase II

Supportive medications:

28-day cycle x up to 9 cycles

References

  1. Palladini G, Perfetti V, Obici L, Caccialanza R, Semino A, Adami F, Cavallero G, Rustichelli R, Virga G, Merlini G. Association of melphalan and high-dose dexamethasone is effective and well tolerated in patients with AL (primary) amyloidosis who are ineligible for stem cell transplantation. Blood. 2004 Apr 15;103(8):2936-8. Epub 2003 Dec 18. link to original article contains protocol PubMed
    1. Update: Palladini G, 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
  2. Retrospective: Wechalekar AD, Schonland SO, Kastritis E, Gillmore JD, Dimopoulos MA, Lane T, Foli A, Foard D, Milani P, Rannigan L, Hegenbart U, Hawkins PN, Merlini G, Palladini G. A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. Blood. 2013 Apr 25;121(17):3420-7. Epub 2013 Mar 11. link to original article PubMed Melphalan & dexamethasone (MDex) only regimen explicitly mentioned in cohort. Others included thalidomide combination, bortezomib combination, and lenalidomide combination.

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.

Supportive medications:

28-day cycle x 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.

Supportive medications:

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

28-day cycle x up to 9 cycles

References

  1. 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
  2. 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

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 in Kastritis et al. 2012, which had no dose-limiting toxicities.

Supportive medications:

28-day cycle x 12 cycles

References

  1. 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

VMD

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VMD: Velcade (Bortezomib), Melphalan, Dexamethasone

Regimen

Phase II

4 to 6 week cycles x up to 20 cycles

References

  1. 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

Lenalidomide & Dexamethasone

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Regimen

Study Evidence
Cibeira et al. 2015 Phase II

Treatment preceded by LDC x 12.

Supportive medications:

OR

28-day cycle x 3 years

References

  1. 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

Relapsed/refractory

Bortezomib (Velcade)

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Regimen #1, Reece et al. 2011 - twice per week (CAN2007)

Phase II

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

Regimen #2, Reece et al. 2011 - weekly schedule (CAN2007)

Phase II

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

References

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

CRD

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CRD: Cyclophosphamide, Revlimid (Lenalidomide), Dexamethasone

Regimen

Phase II

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 x up to 9 cycles or 2 years, depending on reference

References

  1. 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
  2. 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, Wechalekar et al. 2007

Phase II

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, Wechalekar et al. 2007 - risk attenuated regimen

Phase II

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

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

  1. 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.

Supportive medications:

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.

28-day cycle with target 12 total cycles, could continue if response observed

References

  1. 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
  2. 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 (Pomalyst)

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Regimen

Phase II

Supportive medications:

  • Aspirin 325 mg PO once per day for thromboprophylaxis

28-day cycles, given until progression of disease

References

  1. 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

RdC

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RdC: Revlimid (Lenalidomide), dexamethasone, Cyclophosphamide

Regimen

Phase II

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

Supportive medications:

28-day cycle x 12 cycles

References

  1. 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