Revision as of 02:32, 5 July 2016

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25 regimens on this page 48 variants on this page

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
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
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
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

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

28-day cycle for up to 9 cycles

References

Moreau P, Jaccard A, Benboubker L, Royer B, Leleu X, Bridoux F, Salles G, Leblond V, Roussel M, Alakl M, Hermine O, Planche L, Harousseau JL, Fermand JP. Lenalidomide in combination with melphalan and dexamethasone in patients with newly diagnosed AL amyloidosis: a multicenter phase 1/2 dose-escalation study. Blood. 2010 Dec 2;116(23):4777-82. Epub 2010 Aug 19. link to original article contains verified protocol PubMed
Sanchorawala V, Patel JM, Sloan JM, Shelton AC, Zeldis JB, Seldin DC. Melphalan, lenalidomide and dexamethasone for the treatment of immunoglobulin light chain amyloidosis: results of a phase II trial. Haematologica. 2013 May;98(5):789-92. Epub 2012 Nov 9. link to original article contains verified protocol 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

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
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

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 (Pomalyst)

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Regimen

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

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

@@ Line 44: / Line 44: @@
 |}
 ''Details of dosing not available in the Sanchorawala et al. 2015 abstract.''
-*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
+====Chemotherapy====
+*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> 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 x 2 cycles'''
+'''21-day cycle for 2 cycles'''
 ''Treatment in '''Huang et al. 2014''' followed by [[#Melphalan_-.3E_autologous_stem_cell_transplant|high-dose melphalan -> autologous stem cell transplant]]. Treatment in '''Sanchorawala et al. 2015''' followed by [[#Bortezomib_.26_Melphalan_-.3E_autologous_stem_cell_transplant|bortezomib & high-dose melphalan -> autologous stem cell transplant]].''
@@ Line 78: / Line 79: @@
 |-
 |}
+====Chemotherapy====
-*[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 21
+*[[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 1 to 6: 300 mg/m<sup>2</sup> IV once per day on days 1 & 8
-**Cycles 7 to 12: 300 mg/m2 IV once on day 1
+**Cycles 7 to 12: 300 mg/m<sup>2</sup> IV once on day 1
-Supportive medications:
+====Supportive medications====
 *[[Aspirin]] 100 mg PO once per day, or [[:Category:Low_molecular_weight_heparins|Low molecular weight heparin]]
-Dose reductions:
+'''28-day cycle for 12 cycles'''
-*[[Lenalidomide (Revlimid)]]:
-**GFR below 50: reduce dose to 10 mg
-**GFR below 30: reduce dose to 5 mg
-*[[Dexamethasone (Decadron)]]:
-**Cardiac stage III (this is not defined): upfront modification "allowed" but not defined
-'''28-day cycle x 12 cycles'''
 ''Patients without progression who were tolerating therapy proceeded to [[#Lenalidomide_.26_Dexamethasone|lenalidomide & dexamethasone maintenance]].''
@@ Line 106: / Line 104: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://bloodjournal.hematologylibrary.org/content/119/21/4860.long Kumar et al. 2012]
+|[http://www.bloodjournal.org/content/119/21/4860.long Kumar et al. 2012]
 |<span
 style="background:#EEEE00;
@@ Line 115: / Line 113: @@
 |-
 |}
+====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:
+====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 [[:Category:Low_molecular_weight_heparins|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 x up to 2 years'''
+'''28-day cycle for up to 2 years'''
 ===Regimen #3, "RdC" {{#subobject:92db93|Variant=1}}===
@@ Line 132: / Line 130: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://bloodjournal.hematologylibrary.org/content/119/23/5384.long Kastritis et al. 2012]
+|[http://www.bloodjournal.org/content/119/23/5384.long Kastritis et al. 2012]
 |<span
 style="background:#EEEE00;
@@ Line 143: / Line 141: @@
 ''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:
+====Supportive medications====
 *[[Aspirin]] 100 mg PO once daily for thromboprophylaxis
 *[[:Category:Proton_pump_inhibitors|Proton pump inhibitor]]
@@ Line 153: / Line 152: @@
 *[[Valacyclovir (Valtrex)]], dose and schedule not listed
-'''28-day cycle x 12 cycles'''
+'''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. [http://bloodjournal.hematologylibrary.org/content/119/21/4860.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22504925 PubMed]
+# 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. [http://www.bloodjournal.org/content/119/21/4860.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22504925 PubMed]
 <!-- no pre-pub disclosed -->
-# 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. [http://bloodjournal.hematologylibrary.org/content/119/23/5384.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22517904 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. [http://www.bloodjournal.org/content/119/23/5384.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22517904 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13500/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25974382 PubMed]
@@ Line 172: / Line 171: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://bloodjournal.hematologylibrary.org/content/109/2/457.long Wechalekar et al. 2007]
+|[http://www.bloodjournal.org/content/109/2/457.long Wechalekar et al. 2007]
 |<span
 style="background:#EEEE00;
@@ Line 181: / Line 180: @@
 |-
 |}
+====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:
+====Supportive medications====
 *"Antimicrobial and thromboprophylaxis were given according to local protocol"; no routine thromboprophylaxis
@@ Line 196: / Line 195: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://bloodjournal.hematologylibrary.org/content/109/2/457.long Wechalekar et al. 2007]
+|[http://www.bloodjournal.org/content/109/2/457.long Wechalekar et al. 2007]
 |<span
 style="background:#EEEE00;
@@ Line 207: / Line 206: @@
 ''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:
+====Supportive medications====
 *"Antimicrobial and thromboprophylaxis were given according to local protocol"; no routine thromboprophylaxis
@@ Line 218: / Line 218: @@
 ===References===
 <!-- no pre-pub disclosed -->
-# 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. [http://bloodjournal.hematologylibrary.org/content/109/2/457.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16990593 PubMed]
+# 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. [http://www.bloodjournal.org/content/109/2/457.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16990593 PubMed]
 ==CyBorD {{#subobject:d1f835|Regimen=1}}==
@@ Line 232: / Line 232: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://bloodjournal.hematologylibrary.org/content/119/19/4391.long Mikhael et al. 2012]
+|[http://www.bloodjournal.org/content/119/19/4391.long Mikhael et al. 2012]
 |<span
 style="background:#ff0000;
@@ Line 241: / Line 241: @@
 |-
 |}
+====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 300 mg/m2 PO once per week
+*[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> 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
+*[[Bortezomib (Velcade)]] 1.5 mg/m<sup>2</sup> (route not specified) once per week OR 1.3 mg/m<sup>2</sup> on days 1, 4, 8, 11
 *[[Dexamethasone (Decadron)]] 40 mg (route not specified) once per week
-Supportive medications:
+====Supportive medications====
 *"Antiviral prophylaxis"
-'''28-day cycle x 2 to 6 cycles'''
+'''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. [http://bloodjournal.hematologylibrary.org/content/119/19/4391.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22331188 PubMed]
+# 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. [http://www.bloodjournal.org/content/119/19/4391.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22331188 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. [http://www.haematologica.org/content/99/9/1479.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/24859879 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. [http://www.bloodjournal.org/content/126/5/612.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/25987656 PubMed]
@@ Line 267: / Line 267: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://bloodjournal.hematologylibrary.org/content/109/2/492.full Sanchorwala et al. 2006]
+|[http://www.bloodjournal.org/content/109/2/492.full Sanchorwala et al. 2006]
 |<span
 style="background:#EEEE00;
@@ Line 277: / Line 277: @@
 |}
 ''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:
+====Supportive medications====
 *[[Aspirin]] 81 or 325 mg (physician discretion) PO once per day as prophylaxis
@@ Line 292: / Line 292: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://bloodjournal.hematologylibrary.org/content/109/2/465.long Dispenzieri et al. 2006]
+|[http://www.bloodjournal.org/content/109/2/465.long Dispenzieri et al. 2006]
 |<span
 style="background:#EEEE00;
@@ Line 301: / Line 301: @@
 |-
 |}
+====Chemotherapy====
 *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
@@ Line 309: / Line 309: @@
 ===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. [http://bloodjournal.hematologylibrary.org/content/109/2/492.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16960148 PubMed]
+# 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. [http://www.bloodjournal.org/content/109/2/492.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16960148 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. [http://bloodjournal.hematologylibrary.org/content/109/2/465.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17008538 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. [http://www.bloodjournal.org/content/109/2/465.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17008538 PubMed]
 ==Melphalan & Dexamethasone {{#subobject:c07166|Regimen=1}}==
@@ Line 333: / Line 333: @@
 |-
 |}
+====Chemotherapy====
-*[[Melphalan (Alkeran)]] 10 mg/m2 PO once per day on days 1 to 4
+*[[Melphalan (Alkeran)]] 10 mg/m<sup>2</sup> PO once per day on days 1 to 4
 *[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
-Supportive medications:
+====Supportive medications====
 *[[:Category:Proton_pump_inhibitors|Proton pump inhibitor]]
 *[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] three times per week
-'''1-month cycle x up to 18 cycles'''
+'''1-month cycle for up to 18 cycles'''
 ''Patients achieving complete hematologic remission could stop treatment after 12 cycles.''
@@ Line 350: / Line 350: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://bloodjournal.hematologylibrary.org/content/103/8/2936.long Palladini et al. 2003]
+|[http://www.bloodjournal.org/content/103/8/2936.long Palladini et al. 2003]
 |<span
 style="background:#EEEE00;
@@ Line 359: / Line 359: @@
 |-
 |}
+====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:
+====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 x up to 9 cycles'''
+'''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. [http://bloodjournal.hematologylibrary.org/content/103/8/2936.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15070667 PubMed]
+# 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. [http://www.bloodjournal.org/content/103/8/2936.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15070667 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. [http://www.haematologica.org/content/99/4/743.full link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/24213149 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa070484 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17855669 PubMed]
@@ Line 398: / Line 398: @@
 ''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.''
-*[[Melphalan (Alkeran)]] 5 mg/m2 PO once per day on days 1 to 4
+====Chemotherapy====
+*[[Melphalan (Alkeran)]] 5 mg/m<sup>2</sup> 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:
+====Supportive medications====
 *[[Aspirin]] 325 mg PO once per day to decrease risk of [[Lenalidomide (Revlimid)]]-associated venous thromboembolism (VTE)
 *[[:Category:Proton_pump_inhibitors|Proton pump inhibitor]] to decrease risk of gastritis from [[Dexamethasone (Decadron)]]
-'''28-day cycle x 12 cycles, until progression of disease, or unacceptable toxicity'''
+'''28-day cycle for 12 cycles, until progression of disease, or unacceptable toxicity'''
 ===Regimen #2 {{#subobject:7d51af|Variant=1}}===
@@ Line 413: / Line 414: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://bloodjournal.hematologylibrary.org/content/116/23/4777.long Moreau et al. 2010]
+|[http://www.bloodjournal.org/content/116/23/4777.long Moreau et al. 2010]
 |<span
 style="background:#EEEE00;
@@ Line 423: / Line 424: @@
 |}
 ''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:
+====Supportive medications====
 *[[:Category:Low_molecular_weight_heparins|LMWH]] for the first 4 cycles, then [[Aspirin]] as another option if no thrombosis
-'''28-day cycle x up to 9 cycles'''
+'''28-day cycle for up to 9 cycles'''
 ===References===
 <!-- This work has been presented previously at the 51st American Society of Hematology annual meeting, New Orleans, December 7, 2009, oral presentation, abstract 427; and the XIIth International Symposium on Amyloidosis, Rome, Italy, April 21, 2010, oral presentation, abstract 86. -->
-# 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. [http://bloodjournal.hematologylibrary.org/content/116/23/4777.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20724537 PubMed]
+# 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. [http://www.bloodjournal.org/content/116/23/4777.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20724537 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.  [http://www.haematologica.org/content/early/2012/10/29/haematol.2012.075192.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23144200 PubMed]
@@ Line 459: / Line 460: @@
 |-
 |}
+====Chemotherapy====
-*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 8, 15, 22, '''given first'''
+*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> 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
+**Patients with peripheral neuropathy at baseline received 1.0 mg/m<sup>2</sup> 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'''
+*[[Melphalan (Alkeran)]] 9 mg/m<sup>2</sup> 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
+**Patients with serum creatinine >2.5 mg/dL received 6 mg/m<sup>2</sup> 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 x up to 20 cycles'''
+'''4 to 6 week cycle for up to 20 cycles'''
 ===References===
@@ Line 495: / Line 496: @@
 |}
 ''Treatment preceded by [[#Melphalan_-.3E_autologous_stem_cell_transplant|high-dose melphalan -> autologous stem cell transplant]]. Details of dosing not available in the abstract.''
+====Chemotherapy====
 *[[Bortezomib (Velcade)]]
 *[[Dexamethasone (Decadron)]]
@@ Line 523: / Line 524: @@
 |}
 ''Treatment preceded by [[#Bortezomib_.26_Dexamethasone|bortezomib & dexamethasone]] x 2. Details of dosing not available in the abstract.''
+====Chemotherapy====
 *[[Bortezomib (Velcade)]]
 *[[Melphalan (Alkeran)]]
@@ Line 551: / Line 553: @@
 ''Treatment preceded by [[#CRd.2C_LDC.2C_RdC|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:
+====Supportive medications====
 *[[Aspirin]] 100 mg PO once per day or [[:Category:Low_molecular_weight_heparins|Low molecular weight heparin]]
-'''28-day cycle x 3 years'''
+'''28-day cycle for 3 years'''
 ===References===
@@ Line 582: / Line 584: @@
 |}
-===Regimen #1, Reece et al. 2011 - twice per week (CAN2007) {{#subobject:b37e74|Variant=1}}===
+===Regimen #1, twice per week {{#subobject:b37e74|Variant=1}}===
-<span
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|-
+|[http://www.bloodjournal.org/content/118/4/865.long Reece et al. 2011 (CAN2007)]
+|<span
 style="background:#EEEE00;
 padding:3px 6px 3px 6px;
@@ Line 589: / Line 596: @@
 border-width:2px;
 border-style:solid;">Phase II</span>
+|-
+|}
+====Chemotherapy====
+*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> (route not specified) once per day on days 1, 4, 8, 11
-*[[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'''
-'''21-day cycle x up to 8 cycles, with extended treatment allowed for patients with clear clinical benefit'''
+===Regimen #2, weekly schedule {{#subobject:5be0b9|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
-===Regimen #2, Reece et al. 2011 - weekly schedule (CAN2007) {{#subobject:5be0b9|Variant=1}}===
+|'''Study'''
-<span
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|-
+|[http://www.bloodjournal.org/content/118/4/865.long Reece et al. 2011 (CAN2007)]
+|<span
 style="background:#EEEE00;
 padding:3px 6px 3px 6px;
@@ Line 601: / Line 615: @@
 border-width:2px;
 border-style:solid;">Phase II</span>
+|-
+|}
+====Chemotherapy====
+*[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> (route not specified) once per day on days 1, 8, 15, 22
-*[[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'''
-'''35-day cycle x up to 8 cycles, with extended treatment allowed for patients with clear clinical benefit'''
 ===References===
 <!--
-# Reece DE, Sanchorawala V, Hegenbart U, Merlini G, Palladini G, Fermand JP, Vescio RA, Liu X, Elsayed YA, Cakana A, Comenzo RL; VELCADE CAN2007 Study Group. Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis: results of a phase 1 dose-escalation study. Blood. 2009 Aug 20;114(8):1489-97. Epub 2009 Jun 4. [http://bloodjournal.hematologylibrary.org/content/114/8/1489.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19498019 PubMed] content property of [http://hemonc.org HemOnc.org]
+# Reece DE, Sanchorawala V, Hegenbart U, Merlini G, Palladini G, Fermand JP, Vescio RA, Liu X, Elsayed YA, Cakana A, Comenzo RL; VELCADE CAN2007 Study Group. Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis: results of a phase 1 dose-escalation study. Blood. 2009 Aug 20;114(8):1489-97. Epub 2009 Jun 4. [http://www.bloodjournal.org/content/114/8/1489.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19498019 PubMed] content property of [http://hemonc.org HemOnc.org]
 # '''Retrospective:''' Kastritis E, Wechalekar AD, Dimopoulos MA, Merlini G, Hawkins PN, Perfetti V, Gillmore JD, Palladini G. Bortezomib with or without dexamethasone in primary systemic (light chain) amyloidosis. J Clin Oncol. 2010 Feb 20;28(6):1031-7. Epub 2010 Jan 19. [http://jco.ascopubs.org/content/28/6/1031.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/20085941 PubMed]
 -->
-# 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. [http://bloodjournal.hematologylibrary.org/content/118/4/865.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21562045 PubMed]
+# 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. [http://www.bloodjournal.org/content/118/4/865.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21562045 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. [http://www.bloodjournal.org/content/124/16/2498 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25202139 PubMed]
@@ Line 622: / Line 638: @@
 ===Regimen {{#subobject:97779b|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
-<span
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|-
+|[http://www.bloodjournal.org/content/119/21/4860.long Kumar et al. 2012]
+|<span
+style="background:#EEEE00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase II</span>
+|-
+|[http://www.haematologica.org/content/98/3/433.long Palladini et al. 2012]
+|<span
 style="background:#EEEE00;
 padding:3px 6px 3px 6px;
@@ Line 629: / Line 657: @@
 border-width:2px;
 border-style:solid;">Phase II</span>
+|-
+|}
+====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
@@ Line 635: / Line 665: @@
 **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):
+====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'''
+'''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. [http://bloodjournal.hematologylibrary.org/content/119/21/4860.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22504925 PubMed]
+# 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. [http://www.bloodjournal.org/content/119/21/4860.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22504925 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. [http://www.haematologica.org/content/98/3/433.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22983583 PubMed]
@@ Line 653: / Line 684: @@
 CTD: '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''halidomide, '''<u>D</u>'''examethasone
-===Regimen #1, Wechalekar et al. 2007 {{#subobject:68db56|Variant=1}}===
+===Regimen #1 {{#subobject:68db56|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
-<span
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|-
+|[http://www.bloodjournal.org/content/109/2/457.long Wechalekar et al. 2007]
+|<span
 style="background:#EEEE00;
 padding:3px 6px 3px 6px;
@@ Line 661: / Line 696: @@
 border-width:2px;
 border-style:solid;">Phase II</span>
+|-
+|}
+====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:
+====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 {{#subobject:79cb8f|Variant=1}}===
+===Regimen #2, risk attenuated regimen {{#subobject:79cb8f|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
-<span
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|-
+|[http://www.bloodjournal.org/content/109/2/457.long Wechalekar et al. 2007]
+|<span
 style="background:#EEEE00;
 padding:3px 6px 3px 6px;
@@ Line 679: / Line 720: @@
 border-width:2px;
 border-style:solid;">Phase II</span>
+|-
+|}
 ''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:
+====Supportive medications====
 *"Antimicrobial and thromboprophylaxis were given according to local protocol"; no routine thromboprophylaxis
@@ Line 691: / Line 735: @@
 ===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. [http://bloodjournal.hematologylibrary.org/content/109/2/457.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16990593 PubMed]
+# 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. [http://www.bloodjournal.org/content/109/2/457.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16990593 PubMed]
 ==Lenalidomide & Dexamethasone {{#subobject:50cc20|Regimen=1}}==
@@ Line 704: / Line 748: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://bloodjournal.hematologylibrary.org/content/109/2/492.full Sanchorwala et al. 2006]
+|[http://www.bloodjournal.org/content/109/2/492.full Sanchorwala et al. 2006]
 |<span
 style="background:#EEEE00;
@@ Line 715: / Line 759: @@
 ''Preceded by treatment failure after [[#Lenalidomide_.28Revlimid.29|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:
+====Supportive medications====
 *[[Aspirin]] 81 or 325 mg (physician discretion) PO once per day as thromboprophylaxis
 *[[:Category:Proton_pump_inhibitors|Proton pump inhibitor]]
@@ Line 730: / Line 774: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://bloodjournal.hematologylibrary.org/content/109/2/465.long Dispenzieri et al. 2006]
+|[http://www.bloodjournal.org/content/109/2/465.long Dispenzieri et al. 2006]
 |<span
 style="background:#EEEE00;
@@ Line 740: / Line 784: @@
 |}
 ''Preceded by treatment failure after [[#Lenalidomide_.28Revlimid.29|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
@@ Line 747: / Line 791: @@
 ===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. [http://bloodjournal.hematologylibrary.org/content/109/2/492.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16960148 PubMed]
+# 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. [http://www.bloodjournal.org/content/109/2/492.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16960148 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. [http://bloodjournal.hematologylibrary.org/content/109/2/465.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17008538 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. [http://www.bloodjournal.org/content/109/2/465.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17008538 PubMed]
 ==Pomalidomide (Pomalyst) {{#subobject:77727f|Regimen=1}}==
@@ Line 756: / Line 800: @@
 |}
 ===Regimen {{#subobject:ef8da|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
-<span
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|-
+|[http://www.bloodjournal.org/content/119/23/5397.long Dispenzieri et al. 2012]
+|<span
 style="background:#EEEE00;
 padding:3px 6px 3px 6px;
@@ Line 763: / Line 811: @@
 border-width:2px;
 border-style:solid;">Phase II</span>
+|-
+|}
+====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:
+====Supportive medications====
 *[[Aspirin]] 325 mg PO once per day for thromboprophylaxis
@@ Line 774: / Line 824: @@
 ===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. [http://bloodjournal.hematologylibrary.org/content/119/23/5397.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22493299 PubMed]
+# 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. [http://www.bloodjournal.org/content/119/23/5397.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22493299 PubMed]
 ==RdC {{#subobject:77d387|Regimen=1}}==
@@ Line 784: / Line 834: @@
 ===Regimen {{#subobject:ab62e|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
-<span
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|-
+|[http://www.bloodjournal.org/content/119/23/5384.long Kastritis et al. 2012]
+|<span
 style="background:#EEEE00;
 padding:3px 6px 3px 6px;
@@ Line 791: / Line 845: @@
 border-width:2px;
 border-style:solid;">Phase II</span>
+|-
+|}
-''This was the highest dose level tested in Kastritis et al. 2012, which had no dose-limiting toxicities.''
+''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:
+====Supportive medications====
 *[[Aspirin]] 100 mg PO once per day for thromboprophylaxis
 *Proton pump inhibitor
@@ Line 803: / Line 860: @@
 *[[Valacyclovir (Valtrex)]], dose and schedule not listed
-'''28-day cycle x 12 cycles'''
+'''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. [http://bloodjournal.hematologylibrary.org/content/119/23/5384.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22517904 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. [http://www.bloodjournal.org/content/119/23/5384.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22517904 PubMed]
 [[Category:Chemotherapy regimens]]
 [[Category:Malignant hematology regimens]]
 [[Category:Plasma cell dyscrasia regimens]]

Difference between revisions of "Light-chain (AL) amyloidosis"

Revision as of 02:32, 5 July 2016

Untreated (including transplant ineligible)

Bortezomib & Dexamethasone

Regimen

Chemotherapy

References

CRd, LDC, RdC

Regimen #1, "LDC"

Chemotherapy

Supportive medications

Regimen #2, "CRd"

Chemotherapy

Supportive medications

Regimen #3, "RdC"

Chemotherapy

Supportive medications

References

CTD

Regimen #1

Chemotherapy

Supportive medications

Regimen #2, risk attenuated regimen

Chemotherapy

Supportive medications

References

CyBorD

Regimen

Chemotherapy

Supportive medications

References

Lenalidomide (Revlimid)

Regimen #1, 15 mg dosing

Chemotherapy

Supportive medications

Regimen #2, 25 mg dosing

Chemotherapy

References

Melphalan & Dexamethasone

Regimen #1

Chemotherapy

Supportive medications

Regimen #2

Chemotherapy

Supportive medications

References

MRD

Regimen #1

Chemotherapy

Supportive medications

Regimen #2

Chemotherapy

Supportive medications

References

VMD

Regimen

Chemotherapy

References

Consolidation and/or maintenance after upfront therapy

Bortezomib & Dexamethasone

Regimen

Chemotherapy

References

Bortezomib & Melphalan -> autologous stem cell transplant

Regimen

Chemotherapy

References

Lenalidomide & Dexamethasone

Regimen

Chemotherapy

Supportive medications

References

Melphalan -> autologous stem cell transplant

References

Relapsed/refractory

Bortezomib (Velcade)

Regimen #1, twice per week

Chemotherapy

Regimen #2, weekly schedule

Chemotherapy