Difference between revisions of "Multiple myeloma"
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*[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 21 | *[[Pomalidomide (Pomalyst)]] 4 mg PO once per day on days 1 to 21 | ||
− | *[[Dexamethasone (Decadron)]] 40 mg (>75 years old | + | *[[Dexamethasone (Decadron)]] 40 mg (20 mg for patients >75 years old) PO once per day on days 1, 8, 15, 22 |
Supportive medications: | Supportive medications: |
Revision as of 15:44, 26 October 2015
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Untreated (including transplant ineligible), randomized data
Note: most but not all multiple myeloma first-line regimens specify whether patients are transplant eligible, or not. We will begin to break this section in those respective subsections.
CTD (cyclophosphamide)
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CTD: Cyclophosphamide, Thalidomide, Dexamethasone
Regimen
Study | Evidence | Comparator |
Morgan et al. 2012 (MRC Myeloma IX) | Phase III | CVAD |
- Cyclophosphamide (Cytoxan) 500 mg PO once per week
- Thalidomide (Thalomid) 100 mg PO once per day on days 1 to 21, increasing to 200 mg PO once per day "if tolerated"
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 12 to 15
Supportive medications:
- Venous thromboembolism (VTE) prophylaxis was given at physician discretion, but it was suggested that low-risk patients receive Aspirin and high-risk patients receive Warfarin (Coumadin) or low molecular weight heparin according to risk categories as described by Palumbo A et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008;22(2):414–23. link to original article PubMed
- Patients in the study were randomized to a bisphosphonate and received one of the following until progression:
- Sodium clodronate (Bonefos) 1600 mg PO once per day
- Zoledronic acid (Zometa) 4 mg IV once every 21 to 28 days
21-day cycles x up to 6 cycles
References
- Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Johnson PR, Rudin C, Drayson MT, Owen RG, Ross FM, Russell NH, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Studies Group. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. Haematologica. 2012 Mar;97(3):442-50. Epub 2011 Nov 4. link to original article contains verified protocol PubMed
- Update: Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Cook G, Drayson MT, Owen RG, Ross FM, Jackson G, Child JA. Long-Term Follow-Up of MRC Myeloma IX Trial: Survival Outcomes with Bisphosphonate and Thalidomide Treatment. Clin Cancer Res. 2013 Nov 1;19(21):6030-8. Epub 2013 Aug 30. link to original article PubMed
CVAD
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CVAD: Cyclophosphamide, Vincristine, Adriamycin (Doxorubicin), Dexamethasone
Regimen
Study | Evidence | Comparator |
Morgan et al. 2012 (MRC Myeloma IX) | Phase III | CTD |
The reference paper has unclear wording about the schedule and total number of doses of vincristine and doxorubicin. Please contact the editors of this site if you are able to provide a clarification.
- Cyclophosphamide (Cytoxan) 500 mg PO once per week
- Vincristine (Oncovin) 0.4 mg IV once per day on days 1 to 4
- Doxorubicin (Adriamycin) 9 mg/m2/day (total dose per cycle: 36 mg/m2) IV continuous infusion over 4 days on days 1 to 4
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 12 to 15
Supportive medications:
- Patients in the study were randomized to a bisphosphonate and received one of the following until progression:
- Sodium clodronate (Bonefos) 1600 mg PO once per day
- Zoledronic acid (Zometa) 4 mg IV once every 21 to 28 days
21-day cycles x up to 6 cycles
References
- Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Johnson PR, Rudin C, Drayson MT, Owen RG, Ross FM, Russell NH, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Studies Group. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. Haematologica. 2012 Mar;97(3):442-50. Epub 2011 Nov 4. link to original article contains verified protocol--see comment above PubMed
- Update: Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Cook G, Drayson MT, Owen RG, Ross FM, Jackson G, Child JA. Long-Term Follow-Up of MRC Myeloma IX Trial: Survival Outcomes with Bisphosphonate and Thalidomide Treatment. Clin Cancer Res. 2013 Nov 1;19(21):6030-8. Epub 2013 Aug 30. link to original article PubMed
Dexamethasone (Decadron)
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Regimen #1
Study | Evidence | Comparator | Efficacy | Toxicity |
Rajkumar et al. 2006 | Phase III | TD | Seems to have inferior RR | Superior toxicity |
- Dexamethasone (Decadron) as follows:
- Odd-numbered cycles: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
- Even-numbered cycles: 40 mg PO once per day on days 1 to 4
28-day cycles
Regimen #2
Study | Evidence | Comparator | Efficacy |
Rajkumar et al. 2008 | Phase III | TD | Inferior TTP |
- Dexamethasone (Decadron) as follows:
- Cycles 1 to 4: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
- Cycle 5 onwards: 40 mg PO once per day on days 1 to 4
28-day cycles
References
- Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR; Eastern Cooperative Oncology Group. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol. 2006 Jan 20;24(3):431-6. Epub 2005 Dec 19. link to original article contains protocol PubMed
- Rajkumar SV, Rosiñol L, Hussein M, Catalano J, Jedrzejczak W, Lucy L, Olesnyckyj M, Yu Z, Knight R, Zeldis JB, Bladé J. Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol. 2008 May 1;26(13):2171-7. Epub 2008 Mar 24. link to original article contains verified protocol PubMed
DVD, VAD doxil
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DVD: Doxil (Liposomal Doxorubicin), Vincristine, Dexamethasone
VAD doxil: Vincristine, Adriamycin liposomal (Doxil), Dexamethasone
Regimen #1
Study | Evidence | Comparator | Efficacy |
Rifkin et al. 2006 | Phase III | VAd | Non-inferior ORR |
- Doxorubicin liposomal (Doxil) 40 mg/m2 IV over 1 hour once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose per cycle capped at 2 mg) IV over 5 minutes once on day 1
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
4-week cycles, given until maximal response, progression of disease, or unacceptable toxicity
Regimen #2
Study | Evidence | Comparator | |
Dimopoulos et al. 2003 | Phase III | VAD | |
Zervas et al. 2007 | Phase III | TVAD-Doxil |
- Vincristine (Oncovin) 2 mg IV once on day 1
- Doxorubicin liposomal (Doxil) 40 mg/m2 IV over 1 hour once on day 1
- Dexamethasone (Decadron) as follows:
- Cycles 1 & 3: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
- Cycles 2 & 4: 40 mg PO once per day on days 1 to 4
Supportive medications (which were in the cited Segeren et al. 1999 VAD protocol reference):
- Fluconazole (Diflucan) 200 mg PO once per day
- Trimethoprim/Sulfamethoxazole 960 mg (paper did not specify which component was 960 mg) PO BID for "prophylaxis"
4-week cycles x 4 cycles
References
- Dimopoulos MA, Pouli A, Zervas K, Grigoraki V, Symeonidis A, Repoussis P, Mitsouli C, Papanastasiou C, Margaritis D, Tokmaktsis A, Katodritou I, Kokkini G, Terpos E, Vyniou N, Tzilianos M, Chatzivassili A, Kyrtsonis MC, Panayiotidis P, Maniatis A; Greek Myeloma Study Group. Prospective randomized comparison of vincristine, doxorubicin and dexamethasone (VAD) administered as intravenous bolus injection and VAD with liposomal doxorubicin as first-line treatment in multiple myeloma. Ann Oncol. 2003 Jul;14(7):1039-44. link to original article contains protocol PubMed
- Rifkin RM, Gregory SA, Mohrbacher A, Hussein MA. Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma: a Phase III multicenter randomized trial. Cancer. 2006 Feb 15;106(4):848-58. link to original article contains verified protocol PubMed
- Zervas K, Mihou D, Katodritou E, Pouli A, Mitsouli CH, Anagnostopoulos A, Delibasi S, Kyrtsonis MC, Anagnostopoulos N, Terpos E, Zikos P, Maniatis A, Dimopoulos MA; Greek Myeloma Study Group. VAD-doxil versus VAD-doxil plus thalidomide as initial treatment for multiple myeloma: results of a multicenter randomized trial of the Greek Myeloma Study Group. Ann Oncol. 2007 Aug;18(8):1369-75. link to original article contains verified protocol PubMed
MP, M-DEX
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MP: Melphalan, Prednisone/rednisolone
M-DEX: Melphalan, DEXamethasone
Regimen #1
Study | Evidence | Comparator | Efficacy |
Facon et al. 2005 (IFM 95-01) | Phase III | Dexamethasone | Superior PFS |
- Melphalan (Alkeran) 0.25 mg/kg PO once per day on days 1 to 4
- Prednisone (Sterapred) 2 mg/kg PO once per day on days 1 to 4
6-week cycles x 12 cycles
Regimen #2
Study | Evidence | Comparator | Efficacy |
San Miguel et al. 2008 (VISTA) | Phase III | VMP | Inferior OS |
- Melphalan (Alkeran) 9 mg/m2 PO once per day on days 1 to 4
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 4
6-week cycles x 9 cycles
Regimen #3
Note: Though this regimen is listed in several online references, no primary reference for this exact regimen could be found. Specifically, some references cite the Facon et al. 2006 paper for this regimen, but this regimen is not in that paper. Many additional variations of MP can be found in the Myeloma Trialists' Collaborative Group 1998 Journal of Clinical Oncology paper referenced below.
- Melphalan (Alkeran) 0.15 mg/kg PO once daily on days 1 to 7
- Prednisone (Sterapred) 20 mg PO TID on days 1 to 7
6-week cycles
Regimen #4, Facon et al. 2006, Facon et al. 2007 (IFM 95-01)
Study | Evidence | Comparator | Efficacy |
Facon et al. 2007 (IFM 99-06) | Phase III | MPT | Inferior OS |
- Melphalan (Alkeran) 0.25 mg/kg PO once per day on days 1 to 4
- Dexamethasone (Decadron) as follows:
- Cycles 1 & 2: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
- Cycles 3 to 12: 40 mg PO once per day on days 1 to 4
6-week cycles x 12 cycles
Regimen #5
Study | Evidence | Comparator |
Hulin et al. 2009 (IFM 01/01) | Phase III | MPT |
- Melphalan (Alkeran) 0.2 mg/kg PO once per day on days 1 to 4
- Prednisone (Sterapred) 2 mg/kg PO once per day on days 1 to 4
6-week cycles x 12 cycles
Regimen #6
Study | Evidence | Comparator | Efficacy |
Palumbo et al. 2012 (MM-015) | Phase III | MPR, MPR-R | Inferior PFS |
- Melphalan (Alkeran) 0.18 mg/kg PO once per day on days 1 to 4
- Prednisone (Sterapred) 2 mg/kg PO once per day on days 1 to 4
Supportive medications:
- Aspirin 75 to 100 mg PO once per day as thromboprophylaxis
28-day cycles x 9 cycles
Regimen #7
Study | Evidence | Comparator | Efficacy |
Wijermans et al. 2010 (HOVON 49) | Phase III | MPT | Might have inferior OS |
- Melphalan (Alkeran) 0.25 mg/kg PO once per day on days 1 to 5
- Prednisone (Sterapred) 1 mg/kg PO once per day on days 1 to 5
Supportive medications:
- Bisphosphonate use recommended with Pamidronate (Aredia) or Clodronate (Bonefos); "a maximum treatment period of 2 years was recommended in patients without active disease."
28-day cycles x 8 cycles
Regimen #8
Study | Evidence | Comparator | Efficacy |
Palumbo et al. 2006 | Phase III | MPT | Seems to have inferior PFS |
- Melphalan (Alkeran) 4 mg/m2 PO once per day on days 1 to 7
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 7
28-day cycles x 6 cycles
References
- Kyle RA. Monoclonal gammopathy and multiple myeloma in the elderly. Baillieres Clin Haematol. 1987 Jun;1(2):533-57. PubMed
- Myeloma Trialists' Collaborative Group. Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. J Clin Oncol. 1998 Dec;16(12):3832-42. link to original article contains protocol PubMed
- Facon T, Mary JY, Pégourie B, Attal M, Renaud M, Sadoun A, Voillat L, Dorvaux V, Hulin C, Lepeu G, Harousseau JL, Eschard JP, Ferrant A, Blanc M, Maloisel F, Orfeuvre H, Rossi JF, Azaïs I, Monconduit M, Collet P, Anglaret B, Yakoub-Agha I, Wetterwald M, Eghbali H, Vekemans MC, Maisonneuve H, Troncy J, Grosbois B, Doyen C, Thyss A, Jaubert J, Casassus P, Thielemans B, Bataille R; Intergroupe Francophone du Myélome (IFM) group. Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy. Blood. 2006 Feb 15;107(4):1292-8. Epub 2005 Sep 20. link to original paper contains verified protocol PubMed
- Palumbo A, Bringhen S, Caravita T, Merla E, Capparella V, Callea V, Cangialosi C, Grasso M, Rossini F, Galli M, Catalano L, Zamagni E, Petrucci MT, De Stefano V, Ceccarelli M, Ambrosini MT, Avonto I, Falco P, Ciccone G, Liberati AM, Musto P, Boccadoro M; Italian Multiple Myeloma Network, GIMEMA. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet. 2006 Mar 11;367(9513):825-31. link to original article contains protocol PubMed
- Update: Palumbo A, Bringhen S, Liberati AM, Caravita T, Falcone A, Callea V, Montanaro M, Ria R, Capaldi A, Zambello R, Benevolo G, Derudas D, Dore F, Cavallo F, Gay F, Falco P, Ciccone G, Musto P, Cavo M, Boccadoro M. Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood. 2008 Oct 15;112(8):3107-14. Epub 2008 May 27. link to original article contains protocol PubMed
- Facon T, Mary JY, Hulin C, Benboubker L, Attal M, Pegourie B, Renaud M, Harousseau JL, Guillerm G, Chaleteix C, Dib M, Voillat L, Maisonneuve H, Troncy J, Dorvaux V, Monconduit M, Martin C, Casassus P, Jaubert J, Jardel H, Doyen C, Kolb B, Anglaret B, Grosbois B, Yakoub-Agha I, Mathiot C, Avet-Loiseau H; Intergroupe Francophone du Myélome. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet. 2007 Oct 6;370(9594):1209-18. link to original article contains protocol PubMed content property of HemOnc.org
- San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS, Dmoszynska A, Abdulkadyrov KM, Schots R, Jiang B, Mateos MV, Anderson KC, Esseltine DL, Liu K, Cakana A, van de Velde H, Richardson PG; VISTA Trial Investigators. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008 Aug 28;359(9):906-17. link to original article contains verified protocol PubMed
- Update: Mateos MV, Richardson PG, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS, Dmoszynska A, Abdulkadyrov KM, Schots R, Jiang B, Esseltine DL, Liu K, Cakana A, van de Velde H, San Miguel JF. Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol. 2010 May 1;28(13):2259-66. Epub 2010 Apr 5. link to original article contains protocol PubMed
- Update: San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS, Dmoszynska A, Abdulkadyrov KM, Delforge M, Jiang B, Mateos MV, Anderson KC, Esseltine DL, Liu K, Deraedt W, Cakana A, van de Velde H, Richardson PG. Persistent overall survival benefit and no increased risk of second malignancies with bortezomib-melphalan-prednisone versus melphalan-prednisone in patients with previously untreated multiple myeloma. J Clin Oncol. 2013 Feb 1;31(4):448-55. Epub 2012 Dec 10. link to original article PubMed
- Hulin C, Facon T, Rodon P, Pegourie B, Benboubker L, Doyen C, Dib M, Guillerm G, Salles B, Eschard JP, Lenain P, Casassus P, Azaïs I, Decaux O, Garderet L, Mathiot C, Fontan J, Lafon I, Virion JM, Moreau P. Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial. J Clin Oncol. 2009 Aug 1;27(22):3664-70. Epub 2009 May 18. link to original article contains verified protocol PubMed
- Wijermans P, Schaafsma M, Termorshuizen F, Ammerlaan R, Wittebol S, Sinnige H, Zweegman S, van Marwijk Kooy M, van der Griend R, Lokhorst H, Sonneveld P; Dutch-Belgium Cooperative Group HOVON. Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study. J Clin Oncol. 2010 Jul 1;28(19):3160-6. Epub 2010 Jun 1. link to original article contains verified protocol PubMed
- Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, Gisslinger H, Wiktor-Jedrzejczak W, Zodelava M, Weisel K, Cascavilla N, Iosava G, Cavo M, Kloczko J, Bladé J, Beksac M, Spicka I, Plesner T, Radke J, Langer C, Ben Yehuda D, Corso A, Herbein L, Yu Z, Mei J, Jacques C, Dimopoulos MA; MM-015 Investigators. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012 May 10;366(19):1759-69. Erratum in: N Engl J Med. 2012 Jul 19;367(3):285. link to original article contains verified protocol PubMed
RD, RevDex, Rd, Len-Dex
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RD: Revlimid (Lenalidomide), Dexamethasone
RevDex: Revlimid (Lenalidomide), Dexamethasone
Rd: Revlimid (Lenalidomide), low dose dexamethasone
Len-Dex: Lenalidomide, Dexamethasone
Regimen #1, "Rd"
Study | Evidence | Comparator | |
Rajkumar et al. 2010 (ECOG E4A03) | Phase III | RD | |
Gay et al. 2010 | Non-randomized |
This is the low-dose dexamethasone arm of ECOG E4A03.
- Lenalidomide (Revlimid) 25 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 (as described in Rajkumar et al. 2010):
- One of the following bisphosphonates:
- Pamidronate (Aredia) 90 mg IV over 2 to 4 hours once every 4 weeks
- Zoledronic acid (Zometa) 4 mg IV over 15 minutes once every 4 weeks
- Thromboprophylaxis required
28-day cycles, either given x 4 cycles prior to transplant, or given until progression of disease or unacceptable toxicity
Regimen #2
Study | Evidence | Comparator |
Rajkumar et al. 2010 (ECOG E4A03) | Phase III | Rd |
This is the high-dose dexamethasone arm of ECOG E4A03.
- 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, 9 to 12, 17 to 20
Supportive medications:
- One of the following bisphosphonates:
- Pamidronate (Aredia) 90 mg IV over 2 to 4 hours once every 28 days
- Zoledronic acid (Zometa) 4 mg IV over 15 minutes once every 28 days
- Aspirin (80 mg or 325 mg per physician discretion) once per day as thrombosis prophylaxis.
28-day cycles
References
- Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, Abonour R, Siegel DS, Katz M, Greipp PR; Eastern Cooperative Oncology Group. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2010 Jan;11(1):29-37. Epub 2009 Oct 21. link to original article contains verified protocol PubMed
- Gay F, Rajkumar SV, Coleman M, Kumar S, Mark T, Dispenzieri A, Pearse R, Gertz MA, Leonard J, Lacy MQ, Chen-Kiang S, Roy V, Jayabalan DS, Lust JA, Witzig TE, Fonseca R, Kyle RA, Greipp PR, Stewart AK, Niesvizky R. Clarithromycin (Biaxin)-lenalidomide-low-dose dexamethasone (BiRd) versus lenalidomide-low-dose dexamethasone (Rd) for newly diagnosed myeloma. Am J Hematol. 2010 Sep;85(9):664-9. link to original article contains verified protocol PubMed
RVD, VDR, VRD
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RVD: Revlimid (Lenalidomide), Velcade (Bortezomib), Dexamethasone
VDR: Velcade (Bortezomib), Dexamethasone, Revlimid (Lenalidomide)
VRD: Velcade (Bortezomib), Revlimid (Lenalidomide), Dexamethasone
Regimen
Study | Evidence | Comparator | |
Kumar et al. 2012 (EVOLUTION) | Randomized Phase II, >20 per arm | VDC | |
Kumar et al. 2012 (EVOLUTION) | Randomized Phase II, >20 per arm | VDC-mod | |
Kumar et al. 2012 (EVOLUTION) | Randomized Phase II, >20 per arm | VDCR |
Induction therapy
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 14
- 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, 8, 15
21-day cycles x 8 cycles, then proceed to consolidation:
Consolidation therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
42-day cycles x 4 cycles
Supportive medications:
- Aspirin 325 mg PO once per day
- Warfarin (Coumadin) or Enoxaparin (Lovenox) could be used based on physician discretion
- PCP prophylaxis recommended
- Acyclovir (Zovirax) prophylaxis for Herpes zoster recommended
- Bisphosphonates could be used "as necessary"
References
- Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ, Stewart AK, Turturro F, Rifkin R, Wolf J, Estevam J, Mulligan G, Shi H, Webb IJ, Rajkumar SV. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012 May 10;119(19):4375-82. Epub 2012 Mar 15. link to original article contains verified protocol PubMed
RVDC, VDCR
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RVDC: Revlimid (Lenalidomide), Velcade (Bortezomib), Dexamethasone, Cyclophosphamide
VDCR: Velcade (Bortezomib), Dexamethasone, Cyclophosphamide, Revlimid (Lenalidomide)
Regimen
Study | Evidence | Comparator | |
Kumar et al. 2012 (EVOLUTION) | Randomized Phase II, >20 per arm | VDC | |
Kumar et al. 2012 (EVOLUTION) | Randomized Phase II, >20 per arm | VDC-mod | |
Kumar et al. 2012 (EVOLUTION) | Randomized Phase II, >20 per arm | VDR |
Induction therapy
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 14
- 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, 8, 15
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once per day on days 1 & 8
21-day cycles x 8 cycles, then proceed to consolidation:
Consolidation therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
42-day cycles x 4 cycles
Supportive medications:
- Aspirin 325 mg PO once per day
- Warfarin (Coumadin) or Enoxaparin (Lovenox) could be used based on physician discretion
- PCP prophylaxis recommended
- Acyclovir (Zovirax) prophylaxis for Herpes zoster recommended
- Bisphosphonates could be used "as necessary"
References
- Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ, Stewart AK, Turturro F, Rifkin R, Wolf J, Estevam J, Mulligan G, Shi H, Webb IJ, Rajkumar SV. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012 May 10;119(19):4375-82. Epub 2012 Mar 15. link to original article contains verified protocol PubMed
TAD
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TAD: Thalidomide, Adriamycin (Doxorubicin), Dexamethasone
Regimen
To be completed
References
- Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; Dutch-Belgian Hemato-Oncology Group (HOVON). A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. Epub 2009 Oct 30. link to original article PubMed
TD
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TD: Thalidomide, Dexamethasone
Regimen #1
Study | Evidence | Comparator | Efficacy |
Rajkumar et al. 2008 | Phase III | Dexamethasone | Superior TTP |
- Thalidomide (Thalomid) as follows:
- Cycle 1: 50 mg PO once per day on days 1 to 14, then 100 mg PO once per day on days 15 to 28
- Cycle 2 onwards: 200 mg PO once per day on days 1 to 28
- Dexamethasone (Decadron) as folows:
- Cycles 1 to 4: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
- Cycle 5 onwards: 40 mg PO once per day on days 1 to 4
28-day cycles
Regimen #2, Rajkumar et al. 2002
Study | Evidence | Comparator | Efficacy | Toxicity |
Rajkumar et al. 2006 | Phase III | Dexamethasone | Seems to have superior RR | Inferior toxicity |
- Thalidomide (Thalomid) 200 mg PO once per day on days 1 to 28
- Dexamethasone (Decadron) as follows:
- Odd-numbered cycles: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
- Even-numbered cycles: 40 mg PO once per day on days 1 to 4
28-day cycles
Regimen #3
Study | Evidence | Comparator |
Cavo et al. 2010 (GIMEMA MM-BO2005) | Phase III | VTD |
Induction therapy
- Thalidomide (Thalomid) as follows:
- Cycle 1: 100 mg PO once per day on days 1 to 14, then 200 mg PO once per day on days 15 to 21
- Cycles 2 & 3: 200 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 9 to 12
21-day cycles x 3 cycles, then proceed to first stem cell transplant
First stem cell transplant
- Melphalan (Alkeran) 200 mg/m2 (route not specified) once on day -2
- Autologous stem cell rescue
Wait until count recovery, then proceed to thalidomide & dexamethasone therapy
Thalidomide & dexamethasone therapy
- Thalidomide (Thalomid) 100 mg PO once per day
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
28-day cycles for 3 to 6 months, then proceed to second stem cell transplant
Second stem cell transplant
- Melphalan (Alkeran) 200 mg/m2 (route not specified) once on day -2
- Autologous stem cell rescue
Wait until 3 months after second transplant, then proceed to thalidomide & dexamethasone therapy
Thalidomide & dexamethasone therapy
- Thalidomide (Thalomid) 100 mg PO once per day
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 20 to 23
35-day cycles x 2 cycles, then proceed to dexamethasone maintenance therapy
Dexamethasone maintenance therapy
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
28-day cycles until progression, relapse, or undue toxicity
Supportive medications:
- Acyclovir (Zovirax) prophylaxis recommended
Regimen #4
Study | Evidence | Comparator | |
Rosiñol et al. 2012 (PETHEMA GEM05MENOS65) | Phase III | VTD | |
Rosiñol et al. 2012 (PETHEMA GEM05MENOS65) | Phase III | VBMCP/VBAD/B |
- Thalidomide (Thalomid) as follows:
- Cycle 1: 50 mg PO once per day on days 1 to 14, then 100 mg PO once per day on days 15 to 28
- Cycle 2 onwards: Thalidomide (Thalomid) 200 mg PO once per day on days 1 to 28
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 9 to 12
Supportive medications:
- Low-molecular weight heparin or Aspirin recommended
28-day cycles x 6 cycles
Regimen #5
Study | Evidence | Comparator |
Cavo et al. 2005 (Bologna 2002) | Phase III | VAD |
- Thalidomide (Thalomid) as follows:
- Cycle 1: 100 mg PO once per day on days 1 to 14, then 200 mg PO once per day on days 15 to end of month
- Cycles 2 to 4: 200 mg PO once per day on days 1 to end of month
- Dexamethasone (Decadron) as follows:
- Cycles 1 & 3: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
- Cycles 2 & 4: 40 mg PO once per day on days 1 to 4
Monthly cycle x 4 cycles
Responders proceeded to autologous stem cell transplant.
References
- Weber D, Rankin K, Gavino M, Delasalle K, Alexanian R. Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol. 2003 Jan 1;21(1):16-9. link to original article PubMed
- Rajkumar SV, Hayman S, Gertz MA, Dispenzieri A, Lacy MQ, Greipp PR, Geyer S, Iturria N, Fonseca R, Lust JA, Kyle RA, Witzig TE. Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. J Clin Oncol. 2002 Nov 1;20(21):4319-23. link to original article PubMed
- Cavo M, Zamagni E, Tosi P, Tacchetti P, Cellini C, Cangini D, de Vivo A, Testoni N, Nicci C, Terragna C, Grafone T, Perrone G, Ceccolini M, Tura S, Baccarani M; Bologna 2002 study. Superiority of thalidomide and dexamethasone over vincristine-doxorubicindexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood. 2005 Jul 1;106(1):35-9. Epub 2005 Mar 10. link to original article contains protocol PubMed
- Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR; Eastern Cooperative Oncology Group. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol. 2006 Jan 20;24(3):431-6. Epub 2005 Dec 19. link to original article contains protocol PubMed
- Rajkumar SV, Rosiñol L, Hussein M, Catalano J, Jedrzejczak W, Lucy L, Olesnyckyj M, Yu Z, Knight R, Zeldis JB, Bladé J. Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol. 2008 May 1;26(13):2171-7. Epub 2008 Mar 24. link to original article contains verified protocol PubMed
- Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, Di Raimondo F, Crippa C, Zamagni E, Palumbo A, Offidani M, Corradini P, Narni F, Spadano A, Pescosta N, Deliliers GL, Ledda A, Cellini C, Caravita T, Tosi P, Baccarani M; GIMEMA Italian Myeloma Network. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010 Dec 18;376(9758):2075-85. Epub 2010 Dec 9. Erratum in: Lancet. 2011 Nov 26;378(9806):1846. link to original article PubMed
- Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A; GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto) Italian Myeloma Network. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2012 Jul 5;120(1):9-19. Epub 2012 Apr 12. link to original article contains verified protocol PubMed
- Rosiñol L, Oriol A, Teruel AI, Hernández D, López-Jiménez J, de la Rubia J, Granell M, Besalduch J, Palomera L, González Y, Etxebeste MA, Díaz-Mediavilla J, Hernández MT, de Arriba F, Gutiérrez NC, Martín-Ramos ML, Cibeira MT, Mateos MV, Martínez J, Alegre A, Lahuerta JJ, San Miguel J, Bladé J; Programa para el Estudio y la Terapéutica de las Hemopatías Malignas/Grupo Español de Mieloma (PETHEMA/GEM) group. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood. 2012 Aug 3;120(8):1589-96. link to original article contains verified protocol PubMed
VAD (Velcade); PAD
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VAD: Velcade (Bortezomib), Adriamycin (Doxorubicin), Dexamethasone
PAD: PS-341 (Bortezomib), Adriamycin (Doxorubicin), Dexamethasone
Regimen #1
Study | Evidence | Comparator | Efficacy |
Sonneveld et al. 2012 (HOVON-65/GMMG-HD4) | Phase III | VAD | Seems to have superior OS |
Observed efficacy is for induction PAD -> transplant -> maintenance bortezomib compared with induction VAD -> transplant -> maintenance thalidomide.
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Doxorubicin (Adriamycin) 9 mg/m2 IV once per day on days 1 to 4
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
Supportive medications (described in the appendix of Sonneveld et al. 2012):
- One of the following bisphosphonates recommended:
- Pamidronate (Aredia) 90 mg IV once every 4 to 6 weeks x at least 2 years
- Zoledronic acid (Zometa) 4 mg IV once every 4 to 6 weeks x at least 2 years
- Ibandronate (Boniva) 6 mg IV once every 4 to 6 weeks x at least 2 years
- "Prophylactic antibiotics" (no further specifics) during induction therapy
- Erythropoietin and pain medications at physician discretion
- One of the following for Herpes zoster prophylaxis throughout bortezomib induction:
- Acyclovir (Zovirax) 800 mg PO per day (did not specify whether taken once per day or as a divided twice per day dose)
- Valacyclovir (Valtrex) 1000 mg PO per day (did not specify whether taken once per day or as a divided twice per day dose)
28-day cycles x 3 cycles
Stem cells collected 4 to 6 weeks after induction therapy; patients proceed to receive single autologous stem cell transplant (HOVON-65) or tandem autologous stem cell transplant (GMMG-HD4).
Regimen #2
Study | Evidence |
Oakervee et al. 2005 | Phase II |
- Bortezomib (Velcade) 1.3 mg/m2 IV bolus once per day on days 1, 4, 8, 11
- Doxorubicin (Adriamycin) 4.5 to 9 mg/m2 IV once per day on days 1 to 4
- Dexamethasone (Decadron) as follows:
- Cycle 1: 40 mg PO once per day on days 1 to 4, 8 to 11, 15 to 18
- Cycles 2 to 4: 40 mg PO once per day on days 1 to 4
21-day cycles x 4 cycles
References
- Oakervee HE, Popat R, Curry N, Smith P, Morris C, Drake M, Agrawal S, Stec J, Schenkein D, Esseltine DL, Cavenagh JD. PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma. Br J Haematol. 2005 Jun;129(6):755-62. link to original article contains protocol PubMed
- Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012 Aug 20;30(24):2946-55. Epub 2012 Jul 16. link to original article contains verified protocol PubMed
VAD (Vincristine), VAD-P
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VAD: Vincristine, Adriamycin (Doxorubicin), Dexamethasone
VAD-P: Vincristine, Adriamycin (Doxorubicin), Dexamethasone, Prednisone
Regimen #1
Study | Evidence |
Barlogie et al. 1984 | Phase II |
- Vincristine (Oncovin) 0.4 mg/day (total dose per cycle: 1.6 mg) IV continuous infusion over 96 hours on days 1 to 4
- Doxorubicin (Adriamycin) 9 mg/m2/day (total dose per cycle: 36 mg/m2) IV continuous infusion over 96 hours on days 1 to 4
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
Supportive medications:
- Cimetidine (Tagamet) prophylaxis (dose not specified)
- Trimethoprim/Sulfamethoxazole prophylaxis (dose not specified)
Cycle duration not specified; treatment was given "until a maximum reduction in myeloma protein had occurred." Patients received four additional cycles of therapy beyond their best response.
Regimen #2
Study | Evidence |
Segeren et al. 1999 | Phase II |
- Vincristine (Oncovin) 0.4 mg IV over 30 minutes once per day on days 1 to 4
- Doxorubicin (Adriamycin) 9 mg/m2 IV over 30 minutes once per day on days 1 to 4
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20 of odd-numbered cycles only
Supportive medications:
- Fluconazole (Diflucan) 200 mg PO once per day
- Trimethoprim/Sulfamethoxazole 960 mg (paper did not specify which component was 960 mg) PO BID for "prophylaxis"
4-week cycles
Regimen #3
Study | Evidence | Comparator |
Berenson et al. 2002 (SWOG 9210) | Phase III | VAD-P/Q |
- Vincristine (Oncovin) 0.4 mg/day (total dose per cycle: 1.6 mg) IV continuous infusion over 4 days on days 1 to 4
- Doxorubicin (Adriamycin) 9 mg/m2/day (total dose per cycle: 36 mg/m2) IV continuous infusion over 4 days on days 1 to 4
- Poor-risk patients received 6.75 mg/m2/day (total dose 27 mg/m2) in cycle 1, with increase to full dose starting cycle 2 if no undue toxicity
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
- Prednisone (Sterapred) 50 mg PO once per day on days 9, 11, 13, 15, 17, 19
21-day cycles x at least 6 months or until at least 25% regression of disease
Patients with at least 50% regression in 6 months or 25% regression in 9 to 12 months of therapy were then started on prednisone maintenance therapy.
Regimen #4
Study | Evidence | Comparator |
Dimopoulos et al. 2003 | Phase III | VAD Doxil |
- Vincristine (Oncovin) 0.4 mg IV over 30 minutes once per day on days 1 to 4
- Doxorubicin (Adriamycin) 9 mg/m2 IV over 30 minutes once per day on days 1 to 4
- Dexamethasone (Decadron) as follows:
- Cycles 1 & 3: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
- Cycles 2 & 4: 40 mg PO once per day on days 1 to 4
Supportive medications (which were in the cited Segeren et al. 1999 reference):
- Fluconazole (Diflucan) 200 mg PO once per day
- Trimethoprim/Sulfamethoxazole 960 mg (paper did not specify which component was 960 mg) PO BID for "prophylaxis"
4-week cycles x 4 cycles
Regimen #5
Study | Evidence | Comparator | Efficacy |
Rifkin et al. 2006 | Phase III | DVd | Non-inferior ORR |
- Vincristine (Oncovin) 0.4 mg/day (total dose per cycle: 1.6 mg) IV continuous infusion over 96 hours on days 1 to 4
- Doxorubicin (Adriamycin) 9 mg/m2/day (total dose per cycle: 36 mg/m2) IV continuous infusion over 96 hours on days 1 to 4
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
28-day cycles
Regimen #6
Study | Evidence | Comparator | Efficacy |
Harousseau et al. 2010 (IFM 2005-01) | Phase III | VD | Might have inferior PFS |
- Vincristine (Oncovin) 0.4 mg/day (total dose per cycle: 1.6 mg) IV continuous infusion over 4 days on days 1 to 4
- Doxorubicin (Adriamycin) 9 mg/m2/day (total dose per cycle: 36 mg/m2) IV continuous infusion over 4 days on days 1 to 4
- Dexamethasone (Decadron) as follows:
- Cycles 1 & 2: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
- Cycle 3 onwards: 40 mg PO once per day on days 1 to 4
Supportive medications:
- Pamidronate (Aredia) 90 mg or Zoledronic acid (Zometa) 4 mg IV once every 28 days until first transplant
- "Antibiotics, antifungal agents, and antiviral prophylaxis in accordance with local practice."
28-day cycle x 4 cycles
Patients were then randomized to DCEP consolidation or went directly to autologous stem cell transplant.
Regimen #7
Study | Evidence | Comparator |
Cavo et al. 2005 (Bologna 2002) | Phase III | TD |
- Vincristine (Oncovin) 0.4 mg/day (total dose per cycle: 1.6 mg) IV continuous infusion over 4 days on days 1 to 4
- Doxorubicin (Adriamycin) 9 mg/m2/day (total dose per cycle: 36 mg/m2) IV continuous infusion over 4 days on days 1 to 4
- Dexamethasone (Decadron) as follows:
- Cycles 1 & 3: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
- Cycles 2 & 4: 40 mg PO once per day on days 1 to 4
Monthly cycle x 4 cycles
Responders proceeded to autologous stem cell transplant.
Regimen #8
Study | Evidence | Comparator | Efficacy |
Sonneveld et al. 2012 (HOVON-65/GMMG-HD4) | Phase III | PAD | Seems to have inferior OS |
Observed efficacy is for induction PAD -> transplant -> maintenance bortezomib compared with induction VAD -> transplant -> maintenance thalidomide.
- Vincristine (Oncovin) 0.4 mg IV once per day on days 1 to 4
- Doxorubicin (Adriamycin) 9 mg/m2 IV once per day on days 1 to 4
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
Supportive medications (described in the appendix of Sonneveld et al. 2012):
- One of the following bisphosphonates recommended:
- Pamidronate (Aredia) 90 mg IV once every 4 to 6 weeks x at least 2 years
- Zoledronic acid (Zometa) 4 mg IV once every 4 to 6 weeks x at least 2 years
- Ibandronate (Boniva) 6 mg IV once every 4 to 6 weeks x at least 2 years
- "Prophylactic antibiotics" (no further specifics) during induction therapy
- Erythropoietin and pain medications at physician discretion
- One of the following for Herpes zoster prophylaxis throughout bortezomib induction:
- Acyclovir (Zovirax) 800 mg PO per day (did not specify whether taken once per day or as a divided twice per day dose)
- Valacyclovir (Valtrex) 1000 mg PO per day (did not specify whether taken once per day or as a divided twice per day dose)
28-day cycles x 3 cycles
Stem cells collected 4 to 6 weeks after induction therapy; patients proceed to receive single autologous stem cell transplant (HOVON-65) or tandem autologous stem cell transplant (GMMG-HD4).
References
- Barlogie B, Smith L, Alexanian R. Effective treatment of advanced multiple myeloma refractory to alkylating agents. N Engl J Med. 1984 May 24;310(21):1353-6. link to original article contains verified protocol PubMed
- Segeren CM, Sonneveld P, van der Holt B, Baars JW, Biesma DH, Cornellissen JJ, Croockewit AJ, Dekker AW, Fibbe WE, Löwenberg B, van Marwijk Kooy M, van Oers MH, Richel DJ, Schouten HC, Vellenga E, Verhoef GE, Wijermans PW, Wittebol S, Lokhorst HM. Vincristine, doxorubicin and dexamethasone (VAD) administered as rapid intravenous infusion for first-line treatment in untreated multiple myeloma. Br J Haematol. 1999 Apr;105(1):127-30. link to original article contains verified protocol PubMed
- Berenson JR, Crowley JJ, Grogan TM, Zangmeister J, Briggs AD, Mills GM, Barlogie B, Salmon SE. Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients. Blood. 2002 May 1;99(9):3163-8. link to original article contains protocol PubMed
- Dimopoulos MA, Pouli A, Zervas K, Grigoraki V, Symeonidis A, Repoussis P, Mitsouli C, Papanastasiou C, Margaritis D, Tokmaktsis A, Katodritou I, Kokkini G, Terpos E, Vyniou N, Tzilianos M, Chatzivassili A, Kyrtsonis MC, Panayiotidis P, Maniatis A; Greek Myeloma Study Group. Prospective randomized comparison of vincristine, doxorubicin and dexamethasone (VAD) administered as intravenous bolus injection and VAD with liposomal doxorubicin as first-line treatment in multiple myeloma. Ann Oncol. 2003 Jul;14(7):1039-44. link to original article contains protocol PubMed
- Cavo M, Zamagni E, Tosi P, Tacchetti P, Cellini C, Cangini D, de Vivo A, Testoni N, Nicci C, Terragna C, Grafone T, Perrone G, Ceccolini M, Tura S, Baccarani M; Bologna 2002 study. Superiority of thalidomide and dexamethasone over vincristine-doxorubicindexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood. 2005 Jul 1;106(1):35-9. Epub 2005 Mar 10. link to original article contains protocol PubMed
- Rifkin RM, Gregory SA, Mohrbacher A, Hussein MA. Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma: a Phase III multicenter randomized trial. Cancer. 2006 Feb 15;106(4):848-58. link to original article contains verified protocol PubMed
- Harousseau JL, Attal M, Avet-Loiseau H, Marit G, Caillot D, Mohty M, Lenain P, Hulin C, Facon T, Casassus P, Michallet M, Maisonneuve H, Benboubker L, Maloisel F, Petillon MO, Webb I, Mathiot C, Moreau P. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol. 2010 Oct 20;28(30):4621-9. Epub 2010 Sep 7. link to original article contains protocol PubMed
- Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012 Aug 20;30(24):2946-55. Epub 2012 Jul 16. link to original article contains verified protocol PubMed
VAD-P/Q
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VAD-P/Q: Vincristine, Adriamycin (Doxorubicin), Dexamethasone, Prednisone, Quinine
Regimen
Study | Evidence | Comparator |
Berenson et al. 2002 (SWOG 9210) | Phase III | VAD-P |
- Vincristine (Oncovin) 0.4 mg/day (total dose per cycle: 1.6 mg) IV continuous infusion over 4 days on days 2 to 5
- Doxorubicin (Adriamycin) 9 mg/m2/day (total dose per cycle: 36 mg/m2) IV continuous infusion over 4 days on days 2 to 5
- Poor-risk patients received 6.75 mg/m2/day (total dose 27 mg/m2) in cycle 1, with increase to full dose starting cycle 2 if no undue toxicity
- Dexamethasone (Decadron) 40 mg PO once per day on days 2 to 5
- Prednisone (Sterapred) 50 mg PO once per day on days 10, 12, 14, 16, 18, 20
- Quinine (Qualaquin) 400 mg PO TID on days 1 to 6
21-day cycles x at least 6 months or until at least 25% regression of disease
Patients with at least 50% regression in 6 months or 25% regression in 9 to 12 months of therapy were then started on prednisone maintenance therapy.
References
- Berenson JR, Crowley JJ, Grogan TM, Zangmeister J, Briggs AD, Mills GM, Barlogie B, Salmon SE. Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients. Blood. 2002 May 1;99(9):3163-8. link to original article contains protocol PubMed
VD (Velcade)
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VD: Velcade (Bortezomib), Dexamethasone
Regimen #1
Study | Evidence | Comparator | |
Niesvizky et al. 2015 (UPFRONT) | Phase III | VMP | |
Niesvizky et al. 2015 (UPFRONT) | Phase III | VTD |
This regimen was meant for transplant ineligible patients.
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Dexamethasone (Decadron) as follows:
- Cycles 1 to 4: 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
- Cycles 5 to 8: 20 mg PO once per day on days 1, 2, 4, 5
21-day cycle x 8 cycles
Treatment followed by bortezomib maintenance.
Regimen #2
Study | Evidence | Comparator | Efficacy |
Moreau et al. 2011 (IFM 2007-02) | Phase III | vtD | Decreased VGPR rate |
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Dexamethasone (Decadron) as follows:
- Cycles 1 & 2: 40 mg (route not specified) once per day on days 1 to 4, 9 to 12
- Cycles 3 & 4: 40 mg (route not specified) once per day on days 1 to 4
21-day cycle x 4 cycles
All patients then underwent high dose melphalan autologous stem cell transplant.
Regimen #3
Study | Evidence | Comparator | Efficacy |
Harousseau et al. 2010 (IFM 2005-01) | Phase III | VAD | Might have superior PFS |
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Dexamethasone (Decadron) as follows:
- Cycles 1 & 2: 40 mg PO once per day on days 1 to 4, 9 to 12
- Cycles 3 & 4: 40 mg PO once per day on days 1 to 4
Supportive medications:
- One of the following bisphosphonates recommended:
- Pamidronate (Aredia) 90 mg IV once every 4 weeks until first transplant
- Zoledronic acid (Zometa) 4 mg IV once every 4 weeks until first transplant
- "Antibiotics, antifungal agents, and antiviral prophylaxis in accordance with local practice."
21-day cycle x 4 cycles
Patients were then randomized to DCEP consolidation or went directly to autologous stem cell transplant.
References
- Harousseau JL, Attal M, Avet-Loiseau H, Marit G, Caillot D, Mohty M, Lenain P, Hulin C, Facon T, Casassus P, Michallet M, Maisonneuve H, Benboubker L, Maloisel F, Petillon MO, Webb I, Mathiot C, Moreau P. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol. 2010 Oct 20;28(30):4621-9. Epub 2010 Sep 7. link to original article contains verified protocol PubMed
- Subgroup analysis: Avet-Loiseau H, Leleu X, Roussel M, Moreau P, Guerin-Charbonnel C, Caillot D, Marit G, Benboubker L, Voillat L, Mathiot C, Kolb B, Macro M, Campion L, Wetterwald M, Stoppa AM, Hulin C, Facon T, Attal M, Minvielle S, Harousseau JL. Bortezomib plus dexamethasone induction improves outcome of patients with t(4;14) myeloma but not outcome of patients with del(17p). J Clin Oncol. 2010 Oct 20;28(30):4630-4. Epub 2010 Jul 19. link to original article PubMed
- Moreau P, Avet-Loiseau H, Facon T, Attal M, Tiab M, Hulin C, Doyen C, Garderet L, Randriamalala E, Araujo C, Lepeu G, Marit G, Caillot D, Escoffre M, Lioure B, Benboubker L, Pégourié B, Kolb B, Stoppa AM, Fuzibet JG, Decaux O, Dib M, Berthou C, Chaleteix C, Sebban C, Traullé C, Fontan J, Wetterwald M, Lenain P, Mathiot C, Harousseau JL. Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus dexamethasone as induction treatment before autologous stem cell transplantation in newly diagnosed multiple myeloma. Blood. 2011 Nov 24;118(22):5752-8. Epub 2011 Aug 17. link to original article contains verified protocol PubMed
- Niesvizky R, Flinn IW, Rifkin R, Gabrail N, Charu V, Clowney B, Essell J, Gaffar Y, Warr T, Neuwirth R, Zhu Y, Elliott J, Esseltine DL, Niculescu L, Reeves J. Community-Based Phase IIIB Trial of Three UPFRONT Bortezomib-Based Myeloma Regimens. J Clin Oncol. 2015 Jun 8. [Epub ahead of print] link to original article contains verified protocol PubMed
VDC, VDC-mod
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VDC: Velcade (Bortezomib), Dexamethasone, Cyclophosphamide
Regimen #1, VDC
Study | Evidence | Comparator | |
Kumar et al. 2012 (EVOLUTION) | Randomized Phase II, >20 per arm | VDC-mod | |
Kumar et al. 2012 (EVOLUTION) | Randomized Phase II, >20 per arm | VDR | |
Kumar et al. 2012 (EVOLUTION) | Randomized Phase II, >20 per arm | VDCR |
The only difference between this and regimen #2 is the number of cyclophosphamide doses.
Induction
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once per day on days 1 & 8
- 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, 8, 15
Supportive medications:
- Aspirin 325 mg PO once per day
- Warfarin (Coumadin) or Enoxaparin (Lovenox) could be used based on physician discretion
- PCP prophylaxis recommended
- Acyclovir (Zovirax) prophylaxis for Herpes zoster recommended
- Bisphosphonates could be used "as necessary"
21-day cycles x 8 cycles, then
Consolidation
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
Supportive medications:
- Aspirin 325 mg PO once per day
- Warfarin (Coumadin) or Enoxaparin (Lovenox) could be used based on physician discretion
- PCP prophylaxis recommended
- Acyclovir (Zovirax) prophylaxis for Herpes zoster recommended
- Bisphosphonates could be used "as necessary"
42-day cycles x 4 cycles
Regimen #2, "VDC-mod"
Study | Evidence | Comparator | |
Kumar et al. 2012 (EVOLUTION) | Randomized Phase II, <20 in this arm | VDC | |
Kumar et al. 2012 (EVOLUTION) | Randomized Phase II, <20 in this arm | VDR | |
Kumar et al. 2012 (EVOLUTION) | Randomized Phase II, <20 in this arm | VDCR |
This arm only had 17 patients enrolled; other arms of the EVOLUTION trial all had > 20 patients enrolled. The only difference between this and regimen #1 is the number of cyclophosphamide doses.
Induction
- 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, 8, 15
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once per day on days 1, 8, 15
Supportive medications:
- Aspirin 325 mg PO once per day
- Warfarin (Coumadin) or Enoxaparin (Lovenox) could be used based on physician discretion
- PCP prophylaxis recommended
- Acyclovir (Zovirax) prophylaxis for Herpes zoster recommended
- Bisphosphonates could be used "as necessary"
21-day cycles x 8 cycles, then
Consolidation
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
Supportive medications:
- Aspirin 325 mg PO once per day
- Warfarin (Coumadin) or Enoxaparin (Lovenox) could be used based on physician discretion
- PCP prophylaxis recommended
- Acyclovir (Zovirax) prophylaxis for Herpes zoster recommended
- Bisphosphonates could be used "as necessary"
42-day cycles x 4 cycles
References
- Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ, Stewart AK, Turturro F, Rifkin R, Wolf J, Estevam J, Mulligan G, Shi H, Webb IJ, Rajkumar SV. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012 May 10;119(19):4375-82. Epub 2012 Mar 15. link to original article contains verified protocol PubMed
- Meta-Analysis: Leiba M, Kedmi M, Duek A, Freidman T, Weiss M, Leiba R, Nagler A, Avigdor A. Bortezomib-Cyclophosphamide-Dexamethasone (VCD) versus Bortezomib-Thalidomide-Dexamethasone (VTD) -based regimens as induction therapies in newly diagnosed transplant eligible patients with multiple myeloma: a meta-analysis. Br J Haematol. 2014 Sep;166(5):702-10. Epub 2014 May 26. link to original article PubMed
VDD; PAD
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VDD: Velcade (Bortezomib), Doxil (Liposomal doxorubicin), Dexamethasone
PAD: PS-341 (Bortezomib), liposomal Adriamycin (Doxorubicin), Dexamethasone
Regimen #1
Study | Evidence |
Jakubowiak et al. 2009 | Phase II |
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Doxorubicin liposomal (Doxil) 30 mg/m2 IV once on day 4
- Dexamethasone (Decadron) as follows:
- Cycle 1: 40 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
- Cycles 2 to 6: 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
Supportive medications:
- Low-molecular weight heparin 40 mg SC once per day or Aspirin 81 mg PO once per day for DVT prophylaxis
- Acyclovir (Zovirax) 400 mg PO BID for Herpes zoster prophylaxis
21-day cycles x 6 cycles
Regimen #2
Study | Evidence |
Palumbo et al. 2010 | Phase II |
Induction therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Doxorubicin liposomal (Doxil) 30 mg/m2 IV once on day 4
- Dexamethasone (Decadron) as follows:
- Cycle 1: 40 mg PO once per day on days 1 to 4, 8 to 11, 15 to 18
- Cycles 2 to 4: 40 mg PO once per day on days 1 to 4
21-day cycles x 4 cycles, then proceed to stem cell mobilization & reinfusion
Stem cell mobilization & reinfusion
Paper did not describe the full details
- Stem cell mobilization with Cyclophosphamide (Cytoxan) 3000 mg/m2 and G-CSF 10 mcg/kg
- Melphalan (Alkeran) 100 mg/m2, given twice, then followed by stem-cell reinfusion
Consolidation
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
- Prednisone (Sterapred) 50 mg PO once every other day
28-day cycles x 4 cycles, then proceed to maintenance therapy
Maintenance
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
28-day cycles, given until relapsed disease
Supportive medications:
- Aspirin 100 mg PO once per day during Lenalidomide (Revlimid) treatment
- Acyclovir (Zovirax) recommended during Bortezomib (Velcade) therapy
References
- Jakubowiak AJ, Kendall T, Al-Zoubi A, Khaled Y, Mineishi S, Ahmed A, Campagnaro E, Brozo C, Braun T, Talpaz M, Kaminski MS. Phase II trial of combination therapy with bortezomib, pegylated liposomal doxorubicin, and dexamethasone in patients with newly diagnosed myeloma. J Clin Oncol. 2009 Oct 20;27(30):5015-22. Epub 2009 Sep 8. link to original article contains verified protocol PubMed
- Update: Dytfeld D, Griffith KA, Friedman J, Lebovic D, Harvey C, Kaminski MS, Jakubowiak AJ. Superior overall survival of patients with myeloma achieving very good partial response or better to initial treatment with bortezomib, pegylated liposomal doxorubicin, and dexamethasone, predicted after two cycles by a free light chain- and M-protein-based model: extended follow-up of a phase II trial. Leuk Lymphoma. 2011 Jul;52(7):1271-80. link to original article contains verified protocol PubMed
- Palumbo A, Gay F, Falco P, Crippa C, Montefusco V, Patriarca F, Rossini F, Caltagirone S, Benevolo G, Pescosta N, Guglielmelli T, Bringhen S, Offidani M, Giuliani N, Petrucci MT, Musto P, Liberati AM, Rossi G, Corradini P, Boccadoro M. Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients. J Clin Oncol. 2010 Feb 10;28(5):800-7. Epub 2010 Jan 4. Erratum in: J Clin Oncol. 2010 May 1;28(13):2314. link to original article contains verified protocol PubMed
- Update: Gay F, Magarotto V, Crippa C, Pescosta N, Guglielmelli T, Cavallo F, Pezzatti S, Ferrari S, Liberati AM, Oliva S, Patriarca F, Offidani M, Omedé P, Montefusco V, Petrucci MT, Giuliani N, Passera R, Pietrantuono G, Boccadoro M, Corradini P, Palumbo A. Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results. Blood. 2013 Aug 22;122(8):1376-83. Epub 2013 Jun 17. link to original article contains protocol PubMed
VTD
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VTD: Velcade (Bortezomib), Thalidomide, Dexamethasone
Regimen #1
Study | Evidence | Comparator |
Niesvizky et al. 2015 (UPFRONT) | Phase III | VD VMP |
This regimen was meant for transplant ineligible patients.
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Thalidomide (Thalomid) 100 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) as follows:
- Cycles 1 to 4: 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
- Cycles 5 to 8: 20 mg PO once per day on days 1, 2, 4, 5
21-day cycle x 8 cycles
Treatment followed by bortezomib maintenance.
Regimen #2
Study | Evidence | Comparator |
Cavo et al. 2010 (GIMEMA MM-BO2005) | Phase III | TD |
Induction therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Thalidomide (Thalomid) as follows:
- Cycle 1: 100 mg PO once per day on days 1 to 14, then 200 mg PO once per day on days 15 to 21
- Cycles 2 & 3: 200 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 40 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
21-day cycle x 3 cycles, then proceed to first stem cell transplant
First stem cell transplant
- Melphalan (Alkeran) 200 mg/m2 once on day -2
- Autologous stem cell rescue
Wait until count recovery, then proceed to thalidomide & dexamethasone therapy
Thalidomide & Dexamethasone therapy
- Thalidomide (Thalomid) 100 mg PO once per day
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
28-day cycle for 3 to 6 months, then proceed to second stem cell transplant
Second stem cell transplant
- Melphalan (Alkeran) 200 mg/m2 once on day -2
- Autologous stem cell rescue
Wait until 3 months after second transplant, then proceed to bortezomib, thalidomide, dexamethasone therapy
Bortezomib, thalidomide, dexamethasone therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
- Thalidomide (Thalomid) 100 mg PO once per day
- Dexamethasone (Decadron) 40 mg PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23
35-day cycle x 2 cycles
Patients then proceed to dexamethasone maintenance therapy.
Supportive medications:
- Acyclovir (Zovirax) prophylaxis recommended
Regimen #3
Study | Evidence | Comparator | Efficacy |
Moreau et al. 2011 (IFM 2007-02) | Phase III | VD | Increased VGPR rate |
- Bortezomib (Velcade) 1 mg/m2 IV once per day on days 1, 4, 8, 11
- Thalidomide (Thalomid) 100 mg PO once per day
- Dexamethasone (Decadron) as follows:
- Cycles 1 & 2: 40 mg (route not specified) once per day on days 1 to 4, 9 to 12
- Cycles 3 & 4: 40 mg (route not specified) once per day on days 1 to 4
21-day cycle x 4 cycles
All patients then underwent high dose melphalan autologous stem cell transplant.
Regimen #4
Study | Evidence | Comparator |
Ludwig et al. 2013 | Randomized Phase II | VTDC |
- Bortezomib (Velcade) 1 .3 mg/m2 IV once per day on days 1, 4, 8, 11
- Thalidomide (Thalomid) 100 mg PO once per day
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 9 to 12
21-day cycle x 4 cycles
Patients who remained eligible for transplant underwent high dose melphalan autologous stem cell transplant. Transplant ineligible patients or patients achieving CR could undergo 4 additional cycles of VTD.
Regimen #5
Study | Evidence | Comparator |
Rosiñol et al. 2012 (PETHEMA GEM05MENOS65) | Phase III | TD VBMCP/VBAD/B |
- Bortezomib (Velcade) 1.3 mg/m2 once per day on days 1, 4, 8, 11
- Thalidomide (Thalomid) as follows:
- Cycle 1: 50 mg PO once per day on days 1 to 14, then 100 mg PO once per day on days 15 to 28
- Cycles 2 to 6: 200 mg PO once per day on days 1 to 28
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 9 to 12
Supportive Medications:
- Low molecular weight heparin (LMWH) or Aspirin recommended
28-day cycle x 6 cycles
Regimen #6, SC Bortezomib
Study | Evidence |
Lok et al. 2014 | Non-randomized |
Induction therapy
- Bortezomib (Velcade) 1 mg/m2 SC once per day on days 1, 4, 8, 11
- Thalidomide (Thalomid) 100 mg PO once per day
- Dexamethasone (Decadron) as follows:
- Cycles 1 & 2: 40 mg (route not specified) once per day on days 1 to 4, 9 to 12
- Cycles 3 & 4: 40 mg (route not specified) once per day on days 1 to 4
21-day cycle x 4 cycles, proceed to stem cell transplant:
Stem cell transplant
- Melphalan (Alkeran) 200 mg/m2 IV
Proceed with consolidation (timing not specified):
Consolidation
- Bortezomib (Velcade) 1 mg/m2 SC once per day on days 1, 4, 8, 11
- Thalidomide (Thalomid) 100 mg PO once per day
- Dexamethasone (Decadron) 40 mg (route not specified) once per day on days 1 to 4
21-day cycle x 2 cycles
Regimen #7
Study | Evidence |
Kaufman et al. 2010 | Retrospective |
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Thalidomide (Thalomid) 100 mg PO once per day
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 9 to 12
Supportive medications:
- Aspirin prophylaxis to decrease risk of DVTs
- Prophylactic "treatment with antiviral and antibiotic medications"
21-day cycle x 3 to 4 cycles
References
- Retrospective: Kaufman JL, Nooka A, Vrana M, Gleason C, Heffner LT, Lonial S. Bortezomib, thalidomide, and dexamethasone as induction therapy for patients with symptomatic multiple myeloma: a retrospective study. Cancer. 2010 Jul 1;116(13):3143-51. link to original article contains protocol PubMed
- Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, Di Raimondo F, Crippa C, Zamagni E, Palumbo A, Offidani M, Corradini P, Narni F, Spadano A, Pescosta N, Deliliers GL, Ledda A, Cellini C, Caravita T, Tosi P, Baccarani M; GIMEMA Italian Myeloma Network. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010 Dec 18;376(9758):2075-85. Epub 2010 Dec 9. link to original article contains protocol PubMed
- Update: # Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A; GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto) Italian Myeloma Network. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2012 Jul 5;120(1):9-19. Epub 2012 Apr 12. link to original article contains verified protocol PubMed
- Moreau P, Avet-Loiseau H, Facon T, Attal M, Tiab M, Hulin C, Doyen C, Garderet L, Randriamalala E, Araujo C, Lepeu G, Marit G, Caillot D, Escoffre M, Lioure B, Benboubker L, Pégourié B, Kolb B, Stoppa AM, Fuzibet JG, Decaux O, Dib M, Berthou C, Chaleteix C, Sebban C, Traullé C, Fontan J, Wetterwald M, Lenain P, Mathiot C, Harousseau JL. Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus dexamethasone as induction treatment before autologous stem cell transplantation in newly diagnosed multiple myeloma. Blood. 2011 Nov 24;118(22):5752-8. Epub 2011 Aug 17. link to original article contains verified protocol PubMed
- Rosiñol L, Oriol A, Teruel AI, Hernández D, López-Jiménez J, de la Rubia J, Granell M, Besalduch J, Palomera L, González Y, Etxebeste MA, Díaz-Mediavilla J, Hernández MT, de Arriba F, Gutiérrez NC, Martín-Ramos ML, Cibeira MT, Mateos MV, Martínez J, Alegre A, Lahuerta JJ, San Miguel J, Bladé J; Programa para el Estudio y la Terapéutica de las Hemopatías Malignas/Grupo Español de Mieloma (PETHEMA/GEM) group. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood. 2012 Aug 3;120(8):1589-96. link to original article contains verified protocol PubMed
- Ludwig H, Viterbo L, Greil R, Masszi T, Spicka I, Shpilberg O, Hajek R, Dmoszynska A, Paiva B, Vidriales MB, Esteves G, Stoppa AM, Robinson D Jr, Ricci D, Cakana A, Enny C, Feng H, van de Velde H, Harousseau JL. Randomized phase II study of bortezomib, thalidomide, and dexamethasone with or without cyclophosphamide as induction therapy in previously untreated multiple myeloma. J Clin Oncol. 2013 Jan 10;31(2):247-55. Epub 2012 Oct 22. link to original article contains verified protocol PubMed
- Update: Ludwig H, Greil R, Masszi T, Spicka I, Shpilberg O, Hajek R, Dmoszynska A, Paiva B, Vidriales MB, Esteves G, Stoppa AM, Robinson D Jr, Chaturvedi S, Ataman O, Enny C, Feng H, van de Velde H, Viterbo L. Bortezomib, thalidomide and dexamethasone, with or without cyclophosphamide, for patients with previously untreated multiple myeloma: 5-year follow-up. Br J Haematol. 2015 Nov;171(3):344-54. Epub 2015 Jul 7. link to original article PubMed
- Lok A, Mocquard J, Bourcier J, Redelsperger L, Bonnet A, Chauvin C, Thomare P, Mahe B, Touzeau C, Moreau P. Subcutaneous Bortezomib incorporated into the Bortezomib-Thalidomide-Dexamethasone regimen as part of frontline therapy in the context of autologous stem-cell transplantation for multiple myeloma. Haematologica. 2014 Mar;99(3):e33-4. Epub 2014 Feb 14. link to original article contains verified protocol PubMed
- Meta-Analysis: Leiba M, Kedmi M, Duek A, Freidman T, Weiss M, Leiba R, Nagler A, Avigdor A. Bortezomib-Cyclophosphamide-Dexamethasone (VCD) versus Bortezomib-Thalidomide-Dexamethasone (VTD) -based regimens as induction therapies in newly diagnosed transplant eligible patients with multiple myeloma: a meta-analysis. Br J Haematol. 2014 Sep;166(5):702-10. Epub 2014 May 26. link to original article PubMed
- Niesvizky R, Flinn IW, Rifkin R, Gabrail N, Charu V, Clowney B, Essell J, Gaffar Y, Warr T, Neuwirth R, Zhu Y, Elliott J, Esseltine DL, Niculescu L, Reeves J. Community-Based Phase IIIB Trial of Three UPFRONT Bortezomib-Based Myeloma Regimens. J Clin Oncol. 2015 Jun 8. [Epub ahead of print] link to original article contains verified protocol PubMed
VTP
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VTP: Velcade (Bortezomib), Thalidomide, Prednisone
Regimen
Study | Evidence | Comparator | Efficacy |
Mateos et al. 2010 (GEM2005) | Phase III | VMP | Seems to have inferior OS |
Induction therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11, 22, 25, 29, 32
- Thalidomide (Thalomid) 50 mg PO once per day on days 1 to 15, then 100 mg PO once per day on days 16 to 42
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 4
42-day cycle x 1 cycle, then
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
- Thalidomide (Thalomid) 100 mg PO once per day
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 4
35-day cycles x 5 cycles, then
Maintenance therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Only one of the following:
- Prednisone (Sterapred) 50 mg PO once every other day
- Thalidomide (Thalomid) 50 mg PO once per day
3-month cycles x up to 3 years
Supportive medications:
- "Patients with bone disease received bisphosphonates, and prophylactic aciclovir was recommended."
- Patients receiving Thalidomide (Thalomid) needed to have thromboprophylaxis with either Aspirin or low-molecular-weight heparin
References
- Mateos MV, Oriol A, Martínez-López J, Gutiérrez N, Teruel AI, de Paz R, García-Laraña J, Bengoechea E, Martín A, Mediavilla JD, Palomera L, de Arriba F, González Y, Hernández JM, Sureda A, Bello JL, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, García-Sanz R, Cibeira MT, Ramos ML, Vidriales MB, Paiva B, Montalbán MA, Lahuerta JJ, Bladé J, Miguel JF. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol. 2010 Oct;11(10):934-41. Epub 2010 Aug 23. link to original article contains verified protocol PubMed
- Update: Mateos MV, Oriol A, Martínez-López J, Teruel AI, López de la Guía A, López J, Bengoechea E, Pérez M, Martínez R, Palomera L, de Arriba F, González Y, Hernández JM, Granell M, Bello JL, Bargay J, Peñalver FJ, Martín-Mateos ML, Paiva B, Montalbán MA, Bladé J, Lahuerta JJ, San-Miguel JF. Update of the GEM2005 trial comparing VMP/VTP as induction in elderly multiple myeloma patients: do we still need alkylators? Blood. 2014 Aug 7. [Epub ahead of print] link to original article contains verified protocol PubMed
Untreated (including transplant ineligible), non-randomized or retrospective data
Note: most but not all multiple myeloma first-line regimens specify whether patients are transplant eligible, or not. We will begin to break this section in those respective subsections.
BDD
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BDD: Bortezomib, Doxorubicin, Dexamethasone
Regimen
Study | Evidence |
Ludwig et al. 2010 | Phase II |
This is not specifically a first-line regimen but most patients enrolled on the phase II trial were untreated (50 out of 68)
- Bortezomib (Velcade) 1.0 mg/m2 (route not specified) once per day on days 1, 4, 8, 11
- Patients without grade 3 or 4 toxicity during the first two cycles could have bortezomib dose increased to 1.3 mg/m2 (route not specified) once per day on days 1, 4, 8, 11
- Doxorubicin (Adriamycin) 9 mg/m2 IV once per day on days 1 & 4
- Patients without grade 3 or 4 toxicity during the first two cycles could have number of doxorubicin doses increased to 9 mg/m2 IV once per day on days 1, 4, 8, 11
- Dexamethasone (Decadron) 40 mg (route not specified) once per day on days 1, 4, 8, 11
21-day cycles x up to 8 cycles
References
- Ludwig H, Adam Z, Hajek R, Greil R, Tóthová E, Keil F, Autzinger EM, Thaler J, Gisslinger H, Lang A, Egyed M, Womastek I, Zojer N. Light chain-induced acute renal failure can be reversed by bortezomib-doxorubicin-dexamethasone in multiple myeloma: results of a phase II study. J Clin Oncol. 2010 Oct 20;28(30):4635-41. Epub 2010 Sep 7. link to original article contains verified protocol PubMed
BiRD
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BiRD: Biaxin, Revlimid (Lenalidomide), Dexamethasone
Phase II Retrospective improved PFS Retrospective increased toxicity
Regimen
Study | Evidence |
Niesvizky et al. 2007 | Phase II |
- Clarithromycin (Biaxin) as follows:
- Cycle 1: 500 mg PO BID on days 2 to 28
- Cycle 2 onwards: 500 mg PO BID on days 1 to 28
- Lenalidomide (Revlimid) as follows:
- Cycle 1: 25 mg PO once per day on days 3 to 21
- Cycle 2 onwards: 25 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) as follows:
- Cycle 1: 40 mg PO once per day on days 1, 2, 3, 8, 15, 22
- Cycle 2 onwards: 40 mg PO once per day on days 1, 8, 15, 22
Supportive medications:
- Aspirin 81 mg PO once per day
- Omeprazole (Prilosec) 20 mg PO once per day
- Trimethoprim/Sulfamethoxazole (Bactrim DS) PO BID, 3 times a week
28-day cycles
References
- Niesvizky R, Jayabalan DS, Christos PJ, Furst JR, Naib T, Ely S, Jalbrzikowski J, Pearse RN, Zafar F, Pekle K, Larow A, Lent R, Mark T, Cho HJ, Shore T, Tepler J, Harpel J, Schuster MW, Mathew S, Leonard JP, Mazumdar M, Chen-Kiang S, Coleman M. BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone) combination therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma. Blood. 2008 Feb 1;111(3):1101-9. Epub 2007 Nov 7. link to original article contains protocol PubMed
- Update: Rossi A, Mark T, Jayabalan D, Christos P, Zafar F, Pekle K, Pearse R, Chen-Kiang S, Coleman M, Niesvizky R. BiRd (clarithromycin, lenalidomide, dexamethasone): an update on long-term lenalidomide therapy in previously untreated patients with multiple myeloma. Blood. 2013 Mar 14;121(11):1982-1985. Epub 2013 Jan 8. link to original article contains protocol PubMed
- Gay F, Rajkumar SV, Coleman M, Kumar S, Mark T, Dispenzieri A, Pearse R, Gertz MA, Leonard J, Lacy MQ, Chen-Kiang S, Roy V, Jayabalan DS, Lust JA, Witzig TE, Fonseca R, Kyle RA, Greipp PR, Stewart AK, Niesvizky R. Clarithromycin (Biaxin)-lenalidomide-low-dose dexamethasone (BiRd) versus lenalidomide-low-dose dexamethasone (Rd) for newly diagnosed myeloma. Am J Hematol. 2010 Sep;85(9):664-9. link to original article contains protocol PubMed
CAD
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CAD: Cyclophosphamide, Adriamycin (Doxorubicin), Dexamethasone
Regimen
This is reported as a stem cell mobilization regimen but presumably has anti-myeloma activity.
To be completed
References
- Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; Dutch-Belgian Hemato-Oncology Group (HOVON). A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. Epub 2009 Oct 30. link to original article PubMed
CCyd
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CCyd: Carfilzomib, Cyclophosphamide, dexamethasone
Regimen
Study | Evidence |
Bringhen et al. 2014 | Phase II |
- Carfilzomib (Kyprolis) as follows:
- Cycle 1: 20 mg/m2 IV once per day on days 1 & 2 then 36 mg/m2 IV once per day on days 8, 9, 15, 16
- Cycles 2 to 9: 36 mg/m2 IV once per day on days 1, 2, 8, 9, 15, 16
- Cyclophosphamide (Cytoxan) 300 mg/m2 PO once per day on days 1, 8, 15
- Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22
28-day cycles x 9 cycles
Followed by maintenance carfilzomib.
References
- Bringhen S, Petrucci MT, Larocca A, Conticello C, Rossi D, Magarotto V, Musto P, Boccadifuoco L, Offidani M, Omedé P, Gentilini F, Ciccone G, Benevolo G, Genuardi M, Montefusco V, Oliva S, Caravita T, Tacchetti P, Boccadoro M, Sonneveld P, Palumbo A. Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study. Blood. 2014 Jul 3;124(1):63-9. Epub 2014 May 22. link to original article contains verified protocol PubMed
CRd
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CRd: Carfilzomib, Revlimid (Lenalidomide), (low-dose) dexamethasone
Regimen
Study | Evidence |
Korde et al. 2012 | Phase II, <20 patients reported |
It is not clear from the abstract when the 20 mg/m2 vs. 36 mg/m2 dose of carfilzomib is used, nor was it clear what doses were used with oral vs. IV dexamethasone.
- Carfilzomib (Kyprolis) 20 or 36 mg/m2 IV once per day on days 1, 2, 8, 9, 15, 16
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 10 or 20 mg IV/PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23
28-day cycle x 8 cycles; patients who had at least stable disease then received:
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
28-day cycle x 12 cycles
References
- Abstract: Korde, Neha; Zingone, Adriana; Kwok, Mary; Manasanch, Elisabet E.; Costello, Rene; Zuchlinski, Diamond; Mulquin, Marcia; Maric, Irina; Calvo, Katherine R; Braylan, Raul C.; Yuan, Constance; Tembhare, Prashant Ramesh; Stetler-Stevenson, Maryalice; Arthur, Diane C; Raffeld, Mark; Xi, Liqiang; Choyke, Peter; Kurdziel, Karen; Lindenberg, Liza; Steinberg, Seth M.; Roschewski, Mark; Landgren, Ola. Phase II Clinical and Correlative Study of Carfilzomib, Lenalidomide, and Dexamethasone (CRd) in Newly Diagnosed Multiple Myeloma (MM) Patients ASH Annual Meeting Abstracts 2012 120: 732 link to abstract
CyBorD
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CyBorD: Cyclophosphamide, Bortezomib, Dexamethasone
Regimen #1, once per week bortezomib
Study | Evidence |
Reeder et al. 2010 | Phase II |
This regimen was described in a letter to the editor of Blood.
- Cyclophosphamide (Cytoxan) 300 mg/m2 PO once per day on days 1, 8, 15, 22
- Bortezomib (Velcade) 1.5 mg/m2 IV once per day on days 1, 8, 15, 22
- Dexamethasone (Decadron) as follows:
- Cycles 1 & 2: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
- Cycles 3 & 4: 40 mg PO once per week
28-day cycles x 4 cycles
Regimen #2
Study | Evidence |
Reeder et al. 2009 | Phase II |
- Cyclophosphamide (Cytoxan) 300 mg/m2 PO once per day on days 1, 8, 15, 22
- 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 to 4, 9 to 12, 17 to 20
Supportive medications:
- Proton pump inhibitor (PPI)
- Acyclovir (Zovirax)
- Quinolone antibiotic
- Antifungal mouthwash recommended
28-day cycles x 4 to 12 cycles
References
- Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Hentz J, Noble B, Pirooz NA, Spong JE, Piza JG, Zepeda VH, Mikhael JR, Leis JF, Bergsagel PL, Fonseca R, Stewart AK. Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia. 2009 Jul;23(7):1337-41. Epub 2009 Feb 19. link to original article contains protocol PubMed
- Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Laumann K, Hentz J, Pirooz NA, Piza JG, Tiedemann R, Mikhael JR, Bergsagel PL, Leis JF, Fonseca R, Stewart AK. Once- versus twice-weekly bortezomib induction therapy with CyBorD in newly diagnosed multiple myeloma. Blood. 2010 Apr 22;115(16):3416-7. link to original letter contains verified protocol PubMed
CYKLONE
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CYKLONE: Cyclophosphamide, Kyprolis (Carfilzomib), ThaLlidomide, DexamethasONE
Regimen
Study | Evidence |
Mikhael et al. 2015 | Phase II |
The carfilzomib dose here is the MTD dose, tested in N=29 patients.
- Cyclophosphamide (Cytoxan) 300 mg/m2 PO on days 1, 8, 15
- Carfilzomib (Kyprolis) as follows:
- Cycle 1: 20 mg/m2 IV once per day on days 1, 2, 8, 9, 15, 16
- Cycle 2 onwards: 36 mg/m2 IV once per day on days 1, 2, 8, 9, 15, 16
- Thalidomide (Thalomid) 100 mg PO once per day on days 1 to 28
- Dexamethasone (Decadron) 40 mg PO on days 1, 8, 15, 22
Supportive medications:
- Aspirin or LMWH for patients intolerant of aspirin
- Acyclovir (Zovirax) 400 mg PO BID
- Antibacterials (not further specified)
- 250 to 500 ml of IVF prior to cycle 1 doses of Carfilzomib (Kyprolis) and then only for patients "at risk for tumor lysis syndrome" in subsequent cycles
28-day cycle x 4 to 12 cycles
The authors state that patients could proceed to autologous stem cell transplant after four cycles but do not provide criteria to undergo transplant as opposed to continuing CYKLONE.
References
- Mikhael JR, Reeder CB, Libby EN, Costa LJ, Bergsagel PL, Buadi F, Mayo A, Nagi Reddy SK, Gano K, Dueck AC, Stewart AK. Phase Ib/II trial of CYKLONE (cyclophosphamide, carfilzomib, thalidomide and dexamethasone) for newly diagnosed myeloma. Br J Haematol. 2015 Apr;169(2):219-27. Epub 2015 Feb 13. link to original article contains verified protocol PubMed
DVd
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DVd: Doxil (Liposomal Doxorubicin), Vincristine, reduced-dose dexamethasone
Regimen
Study | Evidence |
Hussein et al. 2002 | Phase II |
- Doxorubicin liposomal (Doxil) 40 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
- Dexamethasone (Decadron) 40 mg PO/IV once per day on days 1 to 4
Supportive medications:
- Vitamin B6 200 mg PO once per day to help reduce risk of palmar-plantar erythrodysesthesia (PPE)
4-week cycle x 6 to 8 cycles
References
- Hussein MA, Wood L, Hsi E, Srkalovic G, Karam M, Elson P, Bukowski RM. A Phase II trial of pegylated liposomal doxorubicin, vincristine, and reduced-dose dexamethasone combination therapy in newly diagnosed multiple myeloma patients. Cancer. 2002 Nov 15;95(10):2160-8. link to original article contains protocol PubMed
KTd
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KTd: Kyprolis (Carfilzomib), Thalidomide, dexamethasone
Regimen
Study | Evidence |
Sonneveld et al. 2014 | Phase II |
Three cohorts are reported; optimal dose of carfilzomib is not described.
- Carfilzomib (Kyprolis) as follows:
- Cycle 1: 20 mg/m2 IV once per day on days 1 & 2, and:
- Cohort 1: 27 mg/m2 IV once per day on days 8, 9, 15, 16 of cycle 1 and days 1, 2, 8, 9, 15, 16 of subsequent cycles
- Cohort 2: 36 mg/m2 IV once per day on days 8, 9, 15, 16 of cycle 1 and days 1, 2, 8, 9, 15, 16 of subsequent cycles
- Cohort 3: 45 mg/m2 IV once per day on days 8, 9, 15, 16 of cycle 1 and days 1, 2, 8, 9, 15, 16 of subsequent cycles
- Thalidomide (Thalomid) 200 mg PO once per day
- Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22
28-day cycle x 4 cycles
Treatment followed by high-dose melphalan with stem cell rescue.
References
- Sonneveld P, Asselbergs E, Zweegman S, van der Holt B, Kersten MJ, Vellenga E, van Marwijk-Kooy M, Broyl A, de Weerdt O, Lonergan S, Palumbo A, Lokhorst H. Phase 2 study of carfilzomib, thalidomide and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma. Blood. 2015 Jan 15;125(3):449-56. Epub 2014 Nov 14. link to original article contains verified protocol PubMed
RD, RevDex, Rd, Len-Dex
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RD: Revlimid (Lenalidomide), Dexamethasone
RevDex: Revlimid (Lenalidomide), Dexamethasone
Rd: Revlimid (Lenalidomide), low dose dexamethasone
Len-Dex: Lenalidomide, Dexamethasone
Regimen
Study | Evidence |
Rajkumar et al. 2005 | Phase II |
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) as follows:
- Cycles 1 to 4: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
- Cycle 5 onwards: 40 mg PO once per day on days 1 to 4
Supportive medications:
- Aspirin 80 mg or 325 mg (depending on physician choice) PO once per day for thromboprophylaxis
28-day cycles, given until progression of disease or unacceptable toxicity
References
- Rajkumar SV, Hayman SR, Lacy MQ, Dispenzieri A, Geyer SM, Kabat B, Zeldenrust SR, Kumar S, Greipp PR, Fonseca R, Lust JA, Russell SJ, Kyle RA, Witzig TE, Gertz MA. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood. 2005 Dec 15;106(13):4050-3. Epub 2005 Aug 23. link to original article contains protocol PubMed
RVD, VDR, VRD
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RVD: Revlimid (Lenalidomide), Velcade (Bortezomib), Dexamethasone
VDR: Velcade (Bortezomib), Dexamethasone, Revlimid (Lenalidomide)
VRD: Velcade (Bortezomib), Revlimid (Lenalidomide), Dexamethasone
Regimen #1
Study | Evidence |
Roussel et al. 2014 | Phase II |
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 14
- 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, 8, 15
Supportive medications:
- Low–molecular weight heparin (LMWH)
- Antiviral therapy with example valacyclovir given, for herpes zoster prevention
- Antibiotic prophylaxis with example amoxicillin given, for bacterial infections
21-day cycle x 3 cycles
Treatment followed by autologous stem cell transplant.
Regimen #2
Study | Evidence |
Richardson et al. 2010 | Phase II |
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 14
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Dexamethasone (Decadron) 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
Supportive medications:
- Aspirin 81 mg or 325 mg PO once per day
- Antiviral therapy, such as Acyclovir (Zovirax) 400 mg PO once per day
- Bisphosphonate
21-day cycle x 4 to 8 cycles
Patients who responded and tolerated therapy could proceed to maintenance RVD.
References
- Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS, Avigan DE, Xie W, Ghobrial IM, Schlossman RL, Mazumder A, Munshi NC, Vesole DH, Joyce R, Kaufman JL, Doss D, Warren DL, Lunde LE, Kaster S, Delaney C, Hideshima T, Mitsiades CS, Knight R, Esseltine DL, Anderson KC. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010 Aug 5;116(5):679-86. Epub 2010 Apr 12. link to original article contains protocol PubMed
- Roussel M, Lauwers-Cances V, Robillard N, Hulin C, Leleu X, Benboubker L, Marit G, Moreau P, Pegourie B, Caillot D, Fruchart C, Stoppa AM, Gentil C, Wuilleme S, Huynh A, Hebraud B, Corre J, Chretien ML, Facon T, Avet-Loiseau H, Attal M. Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myélome. J Clin Oncol. 2014 Sep 1;32(25):2712-7. Epub 2014 Jul 14. link to original article contains verified protocol PubMed
VAD-DCEP
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VAD: Vincristine, Adriamycin (Doxorubicin), Dexamethasone
DCEP: Dexamethasone, Cyclophosphamide, Etoposide, Platinol (Cisplatin)
Regimen
Study | Evidence |
Corso et al. 2004 | Phase II |
VAD portion
- Vincristine (Oncovin) 2 mg IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Dexamethasone (Decadron) 40 mg IV once per day on days 1 to 4, 14 to 17
Two cycles; time intervals were not specified.
DCEP portion
Stem cells were mobilized and collected after each course of therapy.
- Dexamethasone (Decadron) 40 mg once per day on days 1 to 4
- Cyclophosphamide (Cytoxan) 400 mg/m2/day (total dose per cycle: 1600 mg/m2) IV continuous infusion over 4 days on days 1 to 4
- Etoposide (Vepesid) 40 mg/m2/day (total dose per cycle: 160 mg/m2) IV continuous infusion over 4 days on days 1 to 4
- Cisplatin (Platinol) 10 mg/m2/day (total dose per cycle: 40 mg/m2) IV continuous infusion over 4 days on days 1 to 4
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting 48 hours after chemotherapy and continuing through stem cell collection
Two courses; time intervals were not specified.
Followed by high dose melphalan with autologous stem cell transplant.
References
- Corso A, Barbarano L, Zappasodi P, Cairoli R, Alessandrino EP, Mangiacavalli S, Ferrari D, Fava S, Fiumanò M, Frigerio G, Isa L, Luraschi A, Klersy C, De Paoli A, Vergani C, Banfi L, Perego D, Ucci G, Pinotti G, Savarè M, Uziel L, Vismara A, Morra E, Lazzarino M. The VAD-DCEP sequence is an effective pre-transplant therapy in untreated multiple myeloma. Haematologica. 2004 Sep;89(9):1124-7. link to original article contains verified protocol PubMed
VTD-PACE
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VTD-PACE: Velcade (Bortezomib), Thalidomide, Dexamethasone, Platinum (Cisplatin), Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide
Regimen
Study | Evidence |
Barlogie et al. 2007 (Total Therapy 3) | Prospective |
Induction therapy
- Bortezomib (Velcade) 1.0 mg/m2 SC once per day on days 1, 4, 8, 11
- Thalidomide (Thalomid) 200 mg PO once per day on days 4 to 7
- Dexamethasone (Decadron) 40 mg PO once per day on days 4 to 7
- Cisplatin (Platinol) 10 mg/m2/day (total dose per cycle: 40 mg/m2) IV continuous infusion over 4 days on days 4 to 7
- Doxorubicin (Adriamycin) 10 mg/m2/day (total dose per cycle: 40 mg/m2) IV continuous infusion over 4 days on days 4 to 7
- Cyclophosphamide (Cytoxan) 400 mg/m2/day (total dose per cycle: 1600 mg/m2) IV continuous infusion over 4 days on days 4 to 7
- Etoposide (Vepesid) 40 mg/m2/day (total dose per cycle: 160 mg/m2) IV continuous infusion over 4 days on days 4 to 7
- Peripheral blood stem cells (PBSC) are usually collected during cycle 1--cycle 2 PBSC collection is done if needed--with a median CD34 count of 29 x 106/kg. 87% of collections yielded at least 20 x 106/kg.
Duration of each cycle not specified; 2 cycles total are given, no more than 8 weeks apart
During the interim period between cycle 1 and cycle 2, as well as after cycle 2 and prior to transplant, this is given once platelets have recovered to at least 50 x 109/L:
- Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4
- Thalidomide (Thalomid) 50 mg PO once per day on days 1 to 21
21-day cycles, given between induction cycles and transplant
In other words, the initial therapy consists of: Induction therapy cycle 1, dexamethasone & thalidomide, induction therapy cycle 2, dexamethasone & thalidomide, then transplant.
Supportive medications, as described in Barlogie et al. 2006, which Barlogie et al. 2007 refers to. Note: Barlogie et al. 2007 lists an incorrect title for the reference. See below for the the correct full reference.
- Filgrastim (Neupogen) "was administered to support induction and consolidation chemotherapy regimens"
- "Prophylactic antibiotics, histamine H2 blockers, and recombinant erythropoietin" were given as needed
- Low molecular weight heparin (LMWH) prophylaxis was used for all patients receiving thalidomide
Autologous stem cell transplant
Full details were not provided in Barlogie et al. 2007. Tandem autologous transplants were done between 2 to 6 months apart.
- Melphalan (Alkeran) 200 mg/m2
During the interim period after transplant 1 and transplant 2, patients receive:
- Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4
- Thalidomide (Thalomid) 50 mg PO once per day on days 1 to 21
21-day cycles, given in the time between and after each transplant; if platelets <50 x 109/L, proceed to year 1 of maintenance therapy. Otherwise, if platelets are at least 50 x 109/L, proceed to consolidation therapy.
Consolidation therapy
Cycle 1 of consolidation starts 1.5 to 4 months after the last transplant. Cycle 2 of consolidation starts 2-4 months after cycle 1 of consolidation.
- Bortezomib (Velcade) 1.0 mg/m2 SC once per day on days 1, 4, 8, 11
- Thalidomide (Thalomid) 200 mg PO once per day on days 1 to 4
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
- Cisplatin (Platinol) 7.5 mg/m2/day (total dose per cycle: 30 mg/m2) IV continuous infusion over 4 days on days 1 to 4
- Doxorubicin (Adriamycin) 7.5 mg/m2/day (total dose per cycle: 30 mg/m2) IV continuous infusion over 4 days on days 1 to 4
- Cyclophosphamide (Cytoxan) 300 mg/m2/day (total dose per cycle: 1200 mg/m2) IV continuous infusion over 4 days on days 1 to 4
- Etoposide (Vepesid) 30 mg/m2/day (total dose per cycle: 120 mg/m2) IV continuous infusion over 4 days on days 1 to 4
2 cycles total are given according to the interval specified above, with the interim therapy below used
During the interim period between cycle 1 and cycle 2, as well as after cycle 2 and prior to maintenance therapy, this is given once platelets have recovered to at least 50 x 109/L:
- Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4
- Thalidomide (Thalomid) 100 mg PO once per day on days 1 to 21
21-day cycles, given between consolidation cycles and maintenance
In other words, consolidation therapy consists of: Consolidation therapy cycle 1, dexamethasone & thalidomide, consolidation therapy cycle 2, dexamethasone & thalidomide, then maintenance therapy.
Supportive medications, as described in Barlogie et al. 2006, which Barlogie et al. 2007 refers to. Note: Barlogie et al. 2007 lists an incorrect title for the reference. See below for the the correct full reference.
- Filgrastim (Neupogen) "was administered to support induction and consolidation chemotherapy regimens"
- "Prophylactic antibiotics, histamine H2 blockers, and recombinant erythropoietin" were given as needed
- Low molecular weight heparin (LMWH) prophylaxis was used for all patients receiving thalidomide
Maintenance therapy, year 1 - VTD
Year 1 of maintenance therapy starts 1 to 4 months after consolidation cycle 2.
- Bortezomib (Velcade) 1.0 mg/m2 SC once per day on days 1, 4, 8, 11
- Thalidomide (Thalomid) 100 mg PO once per day on days 1 to 28
- Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4, 8 to 11
28-day cycles x 1 year, then proceed to maintenance therapy years 2 to 3
Maintenance therapy, years 2 & 3 - TD
- Thalidomide (Thalomid) 100 mg PO once every other day
- Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4
28-day cycles x 2 years
References
- Barlogie B, Tricot G, Anaissie E, Shaughnessy J, Rasmussen E, van Rhee F, Fassas A, Zangari M, Hollmig K, Pineda-Roman M, Lee C, Talamo G, Thertulien R, Kiwan E, Krishna S, Fox M, Crowley J. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med. 2006 Mar 9;354(10):1021-30. link to original article supportive medication details PubMed
- Barlogie B, Anaissie E, van Rhee F, Haessler J, Hollmig K, Pineda-Roman M, Cottler-Fox M, Mohiuddin A, Alsayed Y, Tricot G, Bolejack V, Zangari M, Epstein J, Petty N, Steward D, Jenkins B, Gurley J, Sullivan E, Crowley J, Shaughnessy JD Jr. Incorporating bortezomib into upfront treatment for multiple myeloma: early results of total therapy 3. Br J Haematol. 2007 Jul;138(2):176-85. link to original article contains verified protocol PubMed
- Kapoor P, Ramakrishnan V, Rajkumar SV. Bortezomib combination therapy in multiple myeloma. Semin Hematol. 2012 Jul;49(3):228-42. Review. link to original article PubMed
- Retrospective: Abstract: Preet Paul Singh, Wilson I. Gonsalves, Vinay Gupta, Francis Buadi, Martha Lacy, Angela Dispenzieri, Morie Gertz, Suzanne R. Hayman, David Dingli, Stephen J. Russell, John Anthony Lust, Steven R. Zeldenrust, Prashant Kapoor, Arleigh Robertson McCurdy, S. Vincent Rajkumar, Shaji Kumar. Clinical outcomes after intensive VDT-PACE therapy for relapsed multiple myeloma. J Clin Oncol 31, 2013 (suppl; abstr 8600) link to abstract
Untreated, not transplant eligible
CMP
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CMP: Carfilzomib, Melphalan, Prednisone
Regimen
Study | Evidence |
Moreau et al. 2015 | Phase II |
This trial was open to patients older than 65 years of age. Although not explicitly stated, this is considered to be a transplant ineligible population in France. The carfilzomib dose of 36 mg/m2 was considered to be the MTD in this trial.
- Carfilzomib (Kyprolis) as follows:
- Cycle 1: 20 mg/m2 IV once per day on days 1 & 2 then 36 mg/m2 IV once per day on days 8, 9, 22, 23, 29, 30
- Cycles 2 to 9: 36 mg/m2 IV once per day on days 1, 2, 8, 9, 22, 23, 29, 30
- Melphalan (Alkeran) 9 mg/m2/day PO on days 1 to 4
- Prednisone (Sterapred) 60 mg/m2/day PO on days 1 to 4
42-day cycles x 9 cycles
References
- Moreau P, Kolb B, Attal M, Caillot D, Benboubker L, Tiab M, Touzeau C, Leleu X, Roussel M, Chaleteix C, Planche L, Chiffoleau A, Fortin J, Avet-Loiseau H, Mary JY, Hulin C, Facon T. Phase 1/2 study of carfilzomib plus melphalan and prednisone in patients aged over 65 years with newly diagnosed multiple myeloma. Blood. 2015 May 14;125(20):3100-4. Epub 2015 Mar 17. link to original article contains verified protocol PubMed
CTDa (cyclophosphamide)
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CTDa: Cyclophosphamide, Thalidomide, Dexamethasone, attenuated
Regimen
Study | Evidence | Comparator |
Morgan et al. 2011 (MRC Myeloma IX) | Phase III | MP |
- Cyclophosphamide (Cytoxan) 500 mg PO once per week
- Thalidomide (Thalomid) 50 mg PO once per day on days 1 to 28; dose is increased every 4 weeks in 50 mg increments, up 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:
- For the first 12 weeks of treatment, thromboprophylaxis--for example, with Warfarin (Coumadin) or low molecular weight heparin--was recommended
- Patients in the study were randomized to a bisphosphonate and received one of the following until progression:
- Sodium clodronate (Bonefos) 1600 mg PO once per day
- Zoledronic acid (Zometa) 4 mg IV once every 21 to 28 days
28-day cycles x 6 to 9 cycles
References
- Morgan GJ, Davies FE, Gregory WM, Russell NH, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Byrne JL, Roddie H, Rudin C, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA; NCRI Haematological Oncology Study Group. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood. 2011 Aug 4;118(5):1231-8. Epub 2011 Jun 7. link to original article contains verified protocol PubMed
- Update: Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Cook G, Drayson MT, Owen RG, Ross FM, Jackson G, Child JA. Long-Term Follow-Up of MRC Myeloma IX Trial: Survival Outcomes with Bisphosphonate and Thalidomide Treatment. Clin Cancer Res. 2013 Nov 1;19(21):6030-8. Epub 2013 Aug 30. link to original article PubMed
Dexamethasone (Decadron)
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Regimen
Study | Evidence | Comparator | Efficacy |
Facon et al. 2005 (IFM 95-01) | Phase III | MP | Inferior PFS |
- Dexamethasone (Decadron) as follows:
- Cycles 1 & 2: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
- Cycles 3 to 12: 40 mg PO once per day on days 1 to 4
6-week cycles x 12 cycles
References
- Facon T, Mary JY, Pégourie B, Attal M, Renaud M, Sadoun A, Voillat L, Dorvaux V, Hulin C, Lepeu G, Harousseau JL, Eschard JP, Ferrant A, Blanc M, Maloisel F, Orfeuvre H, Rossi JF, Azaïs I, Monconduit M, Collet P, Anglaret B, Yakoub-Agha I, Wetterwald M, Eghbali H, Vekemans MC, Maisonneuve H, Troncy J, Grosbois B, Doyen C, Thyss A, Jaubert J, Casassus P, Thielemans B, Bataille R; Intergroupe Francophone du Myélome (IFM) group. Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy. Blood. 2006 Feb 15;107(4):1292-8. Epub 2005 Sep 20. link to original paper contains protocol PubMed
DEX-IFN
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DEXamethasone, IFN: Interferon alfa-2b
Regimen, Facon et al. 2006 (IFM 95-01)
Study | Evidence | Comparator |
Facon et al. 2005 (IFM 95-01) | Phase III | Dexamethasone; MP, Mel-Dex |
- Dexamethasone (Decadron) as follows:
- Cycles 1 & 2: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
- Cycles 3 to 12: 40 mg PO once per day on days 1 to 4
- Interferon alfa-2b (Intron-A) 3 million units SC 3 times per week; start with dexamethasone and stop on on day 42 of the last cycle of dexamethasone
6-week cycle x 12 cycles
References
- Facon T, Mary JY, Pégourie B, Attal M, Renaud M, Sadoun A, Voillat L, Dorvaux V, Hulin C, Lepeu G, Harousseau JL, Eschard JP, Ferrant A, Blanc M, Maloisel F, Orfeuvre H, Rossi JF, Azaïs I, Monconduit M, Collet P, Anglaret B, Yakoub-Agha I, Wetterwald M, Eghbali H, Vekemans MC, Maisonneuve H, Troncy J, Grosbois B, Doyen C, Thyss A, Jaubert J, Casassus P, Thielemans B, Bataille R; Intergroupe Francophone du Myélome (IFM) group. Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy. Blood. 2006 Feb 15;107(4):1292-8. Epub 2005 Sep 20. link to original paper contains protocol PubMed
MP
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MP: Melphalan, Prednisone/rednisolone
Regimen
Study | Evidence | Comparator |
Morgan et al. 2011 (MRC Myeloma IX) | Phase III | CTDa |
- Melphalan (Alkeran) 7 mg/m2 PO once per day on days 1 to 4
- Prednisolone (Millipred) 40 mg PO once per day on days 1 to 4
Supportive medications:
- Patients in the study were randomized to a bisphosphonate and received one of the following until progression:
- Sodium clodronate (Bonefos) 1600 mg PO once per day
- Zoledronic acid (Zometa) 4 mg IV once every 21 to 28 days
28-day cycles x 6 to 9 cycles
References
- Morgan GJ, Davies FE, Gregory WM, Russell NH, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Byrne JL, Roddie H, Rudin C, Drayson MT, Owen RG, Ross FM, Jackson GH, Child JA; NCRI Haematological Oncology Study Group. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood. 2011 Aug 4;118(5):1231-8. Epub 2011 Jun 7. link to original article contains verified protocol PubMed
- Update: Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Cook G, Drayson MT, Owen RG, Ross FM, Jackson G, Child JA. Long-Term Follow-Up of MRC Myeloma IX Trial: Survival Outcomes with Bisphosphonate and Thalidomide Treatment. Clin Cancer Res. 2013 Nov 1;19(21):6030-8. Epub 2013 Aug 30. link to original article PubMed
MPR, MPR-R, MPL, RP-MPR-RP
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MPR: Melphalan, Prednisone, Revlimid (Lenalidomide)
MPR-R: Melphalan, Prednisone, Revlimid (Lenalidomide), Revlimid (Lenalidomide) maintenance
MPL: Melphalan, Prednisone, Lenalidomide
RP-MPR-RP: Revlimid (Lenalidomide), Prednisone, Melphalan, Prednisone, Revlimid (Lenalidomide), Revlimid (Lenalidomide), Prednisone
Regimen #1 "MPR-R"
Study | Evidence | Comparator | Efficacy |
Palumbo et al. 2007 | Phase II | ||
Palumbo et al. 2012 (MM-015) | Phase III | MPR | Superior PFS |
- Melphalan (Alkeran) 0.18 mg/kg PO once per day on days 1 to 4
- Prednisone (Sterapred) 2 mg/kg PO once per day on days 1 to 4
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
Supportive medications (varies depending on reference):
- Palumbo et al. 2012: Aspirin 75 to 100 mg PO once per day as thromboprophylaxis
- Palumbo et al. 2007: Ciprofloxacin (Cipro) 500 mg PO BID and Aspirin 100 mg PO once per day
28-day cycles x 9 cycles
Followed by lenalidomide maintenance.
Regimen #2
Study | Evidence | Comparator | Efficacy |
Palumbo et al. 2012 (MM-015) | Phase III | MP | Seems to have superior PFS |
Palumbo et al. 2012 (MM-015) | Phase III | MPR-R | Inferior PFS |
- Melphalan (Alkeran) 0.18 mg/kg PO once per day on days 1 to 4
- Prednisone (Sterapred) 2 mg/kg PO once per day on days 1 to 4
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
Supportive medications:
- Aspirin 75 to 100 mg PO once per day as thromboprophylaxis
28-day cycles x 9 cycles
Regimen #3 "RP-MPR-RP"
Study | Evidence |
Falco et al. 2012 | Phase II |
Induction
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
- Prednisone (Sterapred) 50 mg PO three times per week
28-day cycle x 4 cycles
Consolidation
- Melphalan (Alkeran) 2 mg PO three times per week
- Prednisone (Sterapred) 50 mg PO three times per week
- Lenalidomide (Revlimid) 10 or 15 mg PO once per day on days 1 to 21
28-day cycle x 6 cycles, then:
Maintenance therapy
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
- Prednisone (Sterapred) 25 mg PO three times per week
28-day cycles, to continue until relapse, progression, or intolerable side effects
Supportive medications:
- Aspirin 100 ?mg PO once per day as thromboprophylaxis during Lenalidomide (Revlimid) treatment. Unclear from protocol if this also means off weeks.
- Antiviral prophylaxis if history of VZV.
References
- Palumbo A, Falco P, Corradini P, Falcone A, Di Raimondo F, Giuliani N, Crippa C, Ciccone G, Omedè P, Ambrosini MT, Gay F, Bringhen S, Musto P, Foà R, Knight R, Zeldis JB, Boccadoro M, Petrucci MT; GIMEMA--Italian Multiple Myeloma Network. Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report from the GIMEMA--Italian Multiple Myeloma Network. J Clin Oncol. 2007 Oct 1;25(28):4459-65. Epub 2007 Sep 4. link to original article contains verified protocol PubMed
- Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, Gisslinger H, Wiktor-Jedrzejczak W, Zodelava M, Weisel K, Cascavilla N, Iosava G, Cavo M, Kloczko J, Bladé J, Beksac M, Spicka I, Plesner T, Radke J, Langer C, Ben Yehuda D, Corso A, Herbein L, Yu Z, Mei J, Jacques C, Dimopoulos MA; MM-015 Investigators. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012 May 10;366(19):1759-69. Erratum in: N Engl J Med. 2012 Jul 19;367(3):285. link to original article contains verified protocol PubMed
- Falco P, Cavallo F, Larocca A, Rossi D, Guglielmelli T, Rocci A, Grasso M, Siez ML, De Paoli L, Oliva S, Molica S, Mina R, Gay F, Benevolo G, Musto P, Omedè P, Freilone R, Bringhen S, Carella AM, Gaidano G, Boccadoro M, Palumbo A. Lenalidomide-prednisone induction followed by lenalidomide-melphalan-prednisone consolidation and lenalidomide-prednisone maintenance in newly diagnosed elderly unfit myeloma patients. Leukemia. 2013 Mar;27(3):695-701. Epub 2012 Sep 21. link to original article contains verified protocol PubMed
MPT
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MPT: Melphalan, Prednisone, Thalidomide
Regimen #1
Study | Evidence | Comparator | Efficacy |
Benboubker et al. 2014 (FIRST) | Phase III | LD | Seems to have inferior OS |
See supplemental appendix for further details of dose reductions from starting dose.
- Melphalan (Alkeran) starting dose as follows:
- Age ≤75 AND ANC ≥1500 AND Platelets ≥100,000: 0.25 mg/kg PO once per day on days 1 to 4
- Age >75 AND ANC ≥1500 AND Platelets ≥100,000: 0.2 mg/kg PO once per day on days 1 to 4
- Age ≤75 AND ANC <1500 but ≥1000 OR Platelets <100,000 but ≥50,000: 0.125 mg/kg PO once per day on days 1 to 4
- Age >75 AND ANC <1500 but ≥1000 OR Platelets <100,000 but ≥50,000: 0.1 mg/kg PO once per day on days 1 to 4
- Prednisone (Sterapred) 2 mg/kg PO once per day on days 1 to 4
- Thalidomide (Thalomid) starting dose as follows:
- Age ≤75: 200 mg PO once per day
- Age >75: 100 mg PO once per day
42-day cycle x 12 cycles
Regimen #2
Study | Evidence | Comparator | Efficacy |
Facon et al. 2007 (IFM 99-06) | Phase III | MP | Superior OS |
Facon et al. 2007 (IFM 99-06) | Phase III | MEL100 | Seems to have superior OS |
- Melphalan (Alkeran) 0.25 mg/kg PO once per day on days 1 to 4
- Prednisone (Sterapred) 2 mg/kg PO once per day on days 1 to 4
- Thalidomide (Thalomid) 200 mg PO once per day, increased as tolerated after 4 weeks on therapy to maximum dose of 400 mg once per day
42-day cycle x 12 cycles
Regimen #3
Study | Evidence | Comparator | Efficacy |
Wijermans et al. 2010 (HOVON 49) | Phase III | MP | Might have superior OS |
- Melphalan (Alkeran) 0.25 mg/kg PO once per day on days 1 to 5
- Prednisone (Sterapred) 1 mg/kg PO once per day on days 1 to 5
- Thalidomide (Thalomid) 200 mg PO once per day
Supportive medications:
- Bisphosphonate use recommended with Pamidronate (Aredia) or Clodronate (Bonefos); "a maximum treatment period of 2 years was recommended in patients without active disease."
- During induction therapy, low molecular weight heparin use recommended with Nadroparin (Fraxiparine) 2,850 units anti-Xa (for patients >90 kg, dose of 5,700 units anti-Xa)
28-day cycle x 8 cycles
Thalidomide continues at 200 mg PO once per day for 28 days, followed by maintenance thalidomide.
Regimen #4
Study | Evidence | Comparator |
Hulin et al. 2009 (IFM 01/01) | Phase III | MP |
- Melphalan (Alkeran) 0.2 mg/kg PO once per day on days 1 to 4
- Prednisone (Sterapred) 2 mg/kg PO once per day on days 1 to 4
- Thalidomide (Thalomid) 100 mg PO once per day
42-day cycle x 12 cycles
Regimen #5
Study | Evidence | Comparator | Efficacy |
Palumbo et al. 2006 | Phase III | MP | Seems to have superior PFS |
- Melphalan (Alkeran) 4 mg/m2 PO once per day on days 1 to 7
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 7
- Thalidomide (Thalomid) 100 mg PO once per day on days 1 to 28
Supportive medications:
- Enoxaparin (Lovenox) 40 mg SC once per day on days 1 to 28 of cycles 1 to 4
28-day cycle x 6 cycles
Patients then proceeded to maintenance thalidomide.
References
- Palumbo A, Bringhen S, Caravita T, Merla E, Capparella V, Callea V, Cangialosi C, Grasso M, Rossini F, Galli M, Catalano L, Zamagni E, Petrucci MT, De Stefano V, Ceccarelli M, Ambrosini MT, Avonto I, Falco P, Ciccone G, Liberati AM, Musto P, Boccadoro M; Italian Multiple Myeloma Network, GIMEMA. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet. 2006 Mar 11;367(9513):825-31. link to original article contains protocol PubMed
- Update: Palumbo A, Bringhen S, Liberati AM, Caravita T, Falcone A, Callea V, Montanaro M, Ria R, Capaldi A, Zambello R, Benevolo G, Derudas D, Dore F, Cavallo F, Gay F, Falco P, Ciccone G, Musto P, Cavo M, Boccadoro M. Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood. 2008 Oct 15;112(8):3107-14. Epub 2008 May 27. link to original article contains protocol PubMed
- Facon T, Mary JY, Hulin C, Benboubker L, Attal M, Pegourie B, Renaud M, Harousseau JL, Guillerm G, Chaleteix C, Dib M, Voillat L, Maisonneuve H, Troncy J, Dorvaux V, Monconduit M, Martin C, Casassus P, Jaubert J, Jardel H, Doyen C, Kolb B, Anglaret B, Grosbois B, Yakoub-Agha I, Mathiot C, Avet-Loiseau H; Intergroupe Francophone du Myélome. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet. 2007 Oct 6;370(9594):1209-18. link to original article contains verified protocol PubMed content property of HemOnc.org
- Hulin C, Facon T, Rodon P, Pegourie B, Benboubker L, Doyen C, Dib M, Guillerm G, Salles B, Eschard JP, Lenain P, Casassus P, Azaïs I, Decaux O, Garderet L, Mathiot C, Fontan J, Lafon I, Virion JM, Moreau P. Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial. J Clin Oncol. 2009 Aug 1;27(22):3664-70. Epub 2009 May 18. link to original article contains verified protocol PubMed
- Wijermans P, Schaafsma M, Termorshuizen F, Ammerlaan R, Wittebol S, Sinnige H, Zweegman S, van Marwijk Kooy M, van der Griend R, Lokhorst H, Sonneveld P; Dutch-Belgium Cooperative Group HOVON. Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study. J Clin Oncol. 2010 Jul 1;28(19):3160-6. Epub 2010 Jun 1. link to original article contains verified protocol PubMed
- Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch AR, Cavo M, Pinto A, Weisel K, Ludwig H, Bahlis N, Banos A, Tiab M, Delforge M, Cavenagh J, Geraldes C, Lee JJ, Chen C, Oriol A, de la Rubia J, Qiu L, White DJ, Binder D, Anderson K, Fermand JP, Moreau P, Attal M, Knight R, Chen G, Van Oostendorp J, Jacques C, Ervin-Haynes A, Avet-Loiseau H, Hulin C, Facon T; FIRST Trial Team. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014 Sep 4;371(10):906-17. link to original article link to supplemental appendix contains verified protocol PubMed
Rd
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RD: Revlimid (Lenalidomide), Dexamethasone
RevDex: Revlimid (Lenalidomide), Dexamethasone
Rd: Revlimid (Lenalidomide), low dose dexamethasone
Len-Dex: Lenalidomide, Dexamethasone
Regimen #1
Study | Evidence | Comparator | Efficacy |
Benboubker et al. 2014 (FIRST) | Phase III | MPT | Seems to have superior OS |
This was superior to LD18, below. See supplemental appendix for dose adjustments from the starting dose.
- Lenalidomide (Revlimid) starting dose as follows:
- Normal renal function: 25 mg PO once per day on days 1 to 21
- Moderate renal impairment (CrCl 30-50 ml/min): 10 mg PO once per day on days 1 to 21
- Severe renal impairment (CrCl <30 ml/min): 15 mg PO once every other day on days 1 to 21
- Dexamethasone (Decadron) starting dose as follows:
- Age ≤75: 40 mg PO once per day on days 1, 8, 15, 22
- Age >75: 20 mg PO once per day on days 1, 8, 15, 22
28-day cycle given until disease progression
Regimen #2 "LD18"
Study | Evidence | Comparator | Efficacy |
Benboubker et al. 2014 (FIRST) | Phase III | MPT | Seems to not have superior OS |
This was inferior to LD, above. See supplemental appendix for dose adjustments from the starting dose.
- Lenalidomide (Revlimid) starting dose as follows:
- Normal renal function: 25 mg PO once per day on days 1 to 21
- Moderate renal impairment (CrCl 30-50 ml/min): 10 mg PO once per day on days 1 to 21
- Severe renal impairment (CrCl <30 ml/min): 15 mg PO once every other day on days 1 to 21
- Dexamethasone (Decadron) starting dose as follows:
- Age ≤75: 40 mg PO once per day on days 1, 8, 15, 22
- Age >75: 20 mg PO once per day on days 1, 8, 15, 22
28-day cycle x 18 cycles
References
- Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch AR, Cavo M, Pinto A, Weisel K, Ludwig H, Bahlis N, Banos A, Tiab M, Delforge M, Cavenagh J, Geraldes C, Lee JJ, Chen C, Oriol A, de la Rubia J, Qiu L, White DJ, Binder D, Anderson K, Fermand JP, Moreau P, Attal M, Knight R, Chen G, Van Oostendorp J, Jacques C, Ervin-Haynes A, Avet-Loiseau H, Hulin C, Facon T; FIRST Trial Team. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014 Sep 4;371(10):906-17. link to original article link to supplemental appendix contains verified protocol PubMed
VD (Velcade)
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VD: Velcade (Bortezomib), Dexamethasone
Regimen
Study | Evidence |
Girnius et al. 2014 | Phase II |
- Bortezomib (Velcade) 1.6 mg/m2 IV once per week on days 1, 8, 15, 22
- Dexamethasone (Decadron) 40 mg PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23
35-day cycle x up to 6 cycles based on response and tolerance of side effects
References
- Girnius SK, Lee S, Kambhampati S, Rose MG, Mohiuddin A, Houranieh A, Zimelman A, Grady T, Mehta P, Behler C, Hayes TG, Efebera YA, Prabhala RH, Han A, Yellapragada SV, Klein CE, Roodman GD, Lichtenstein A, Munshi NC. A Phase II trial of weekly bortezomib and dexamethasone in veterans with newly diagnosed multiple myeloma not eligible for or who deferred autologous stem cell transplantation. Br J Haematol. 2015 Jan 8. [Epub ahead of print] Epub 2014 Sep 18. link to original article contains verified protocol PubMed
VMP
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VMP: Velcade (Bortezomib), Melphalan, Prednisone
Regimen #1
Study | Evidence | Comparator | |
Niesvizky et al. 2015 (UPFRONT) | Phase III | VD | |
Niesvizky et al. 2015 (UPFRONT) | Phase III | VTD |
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Melphalan (Alkeran) 9 mg/m2 PO once per day on days 1 to 4 every other cycle
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 4 every other cycle
21-day cycle x 8 cycles
Treatment followed by bortezomib maintenance.
Regimen #2
Study | Evidence | Comparator | Efficacy |
San Miguel et al. 2008 (VISTA) | Phase III | MP | Superior OS |
Palumbo et al. 2010 | Phase III | VMPT-VT | Seems to have inferior OS |
- Bortezomib (Velcade) as follows:
- Cycles 1 to 4: 1.3 mg/m2 IV bolus once per day on days 1, 4, 8, 11, 22, 25, 29, 32
- Cycles 5 to 9: 1.3 mg/m2 IV bolus once per day on days 1, 8, 22, 29
- Melphalan (Alkeran) 9 mg/m2 PO once per day on days 1 to 4
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 4
Supportive medication:
- Bisphosphonates given to patients with myeloma-associated bone disease unless contraindicated (only mentioned in San Miguel et al. 2008)
42-day cycle x 9 cycles
Regimen #3
Study | Evidence | Comparator | Efficacy |
Mateos et al. 2010 (GEM2005) | Phase III | VTP | Seems to have superior OS |
Induction therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11, 22, 25, 29, 32
- Melphalan (Alkeran) 9 mg/m2 PO once per day on days 1 to 4
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 4
42-day cycle x 1 cycle, then
- Bortezomib (Velcade) 1.3 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
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 4
35-day cycle x 5 cycles, then
Maintenance therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Only one of the following:
- Prednisone (Sterapred) 50 mg PO once every other day
- Thalidomide (Thalomid) 50 mg PO once per day
3-month cycle x up to 3 years
Supportive medications:
- "Patients with bone disease received bisphosphonates, and prophylactic aciclovir was recommended."
- Patients receiving Thalidomide (Thalomid) needed to have thromboprophylaxis with either aspirin or low molecular weight heparin
Regimen #4, Palumbo et al. 2010 & 2014 & Bringhen et al. 2010 (weekly bortezomib)
Post-hoc analysis
- Bortezomib (Velcade) 1.3 mg/m2 IV bolus once per day on days 1, 8, 15, 22
- Melphalan (Alkeran) 9 mg/m2 PO once per day on days 1 to 4
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 4
35-day cycle x 9 cycles
Regimen #5 "Short-course bortezomib"
Study | Evidence |
Gasparetto et al. 2010 | Phase II |
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Melphalan (Alkeran) 6 mg/m2 PO once per day on days 1 to 7, given at least 1 hour prior to bortezomib
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 7
Supportive medications:
- Bisphosphonates and Acyclovir (Zovirax) recommended
28-day cycle x up to 6 cycles; treatment could be given beyond 6 cycles at investigator discretion
References
- Mateos MV, Hernández JM, Hernández MT, Gutiérrez NC, Palomera L, Fuertes M, Díaz-Mediavilla J, Lahuerta JJ, de la Rubia J, Terol MJ, Sureda A, Bargay J, Ribas P, de Arriba F, Alegre A, Oriol A, Carrera D, García-Laraña J, García-Sanz R, Bladé J, Prósper F, Mateo G, Esseltine DL, van de Velde H, San Miguel JF. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood. 2006 Oct 1;108(7):2165-72. Epub 2006 Jun 13. link to original article PubMed
- Update: Mateos MV, Hernández JM, Hernández MT, Gutiérrez NC, Palomera L, Fuertes M, Garcia-Sanchez P, Lahuerta JJ, de la Rubia J, Terol MJ, Sureda A, Bargay J, Ribas P, Alegre A, de Arriba F, Oriol A, Carrera D, García-Laraña J, García-Sanz R, Bladé J, Prósper F, Mateo G, Esseltine DL, van de Velde H, San Miguel JF. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: updated time-to-events results and prognostic factors for time to progression. Haematologica. 2008 Apr;93(4):560-5. Epub 2008 Mar 5. link to original article PubMed
- San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS, Dmoszynska A, Abdulkadyrov KM, Schots R, Jiang B, Mateos MV, Anderson KC, Esseltine DL, Liu K, Cakana A, van de Velde H, Richardson PG; VISTA Trial Investigators. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008 Aug 28;359(9):906-17. link to original article contains protocol PubMed
- Update: Mateos MV, Richardson PG, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS, Dmoszynska A, Abdulkadyrov KM, Schots R, Jiang B, Esseltine DL, Liu K, Cakana A, van de Velde H, San Miguel JF. Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol. 2010 May 1;28(13):2259-66. Epub 2010 Apr 5. link to original article contains protocol PubMed
- Update: San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, Spicka I, Petrucci MT, Palumbo A, Samoilova OS, Dmoszynska A, Abdulkadyrov KM, Delforge M, Jiang B, Mateos MV, Anderson KC, Esseltine DL, Liu K, Deraedt W, Cakana A, van de Velde H, Richardson PG. Persistent overall survival benefit and no increased risk of second malignancies with bortezomib-melphalan-prednisone versus melphalan-prednisone in patients with previously untreated multiple myeloma. J Clin Oncol. 2013 Feb 1;31(4):448-55. Epub 2012 Dec 10. link to original article PubMed
- Gasparetto C, Gockerman JP, Diehl LF, de Castro CM, Moore JO, Long GD, Horwitz ME, Keogh G, Chute JP, Sullivan KM, Neuwirth R, Davis PH, Sutton LM, Anderson RD, Chao NJ, Rizzieri D. "Short course" bortezomib plus melphalan and prednisone as induction prior to transplant or as frontline therapy for nontransplant candidates in patients with previously untreated multiple myeloma. Biol Blood Marrow Transplant. 2010 Jan;16(1):70-7. Epub 2009 Sep 3. link to original article contains verified protocol PubMed
- Mateos MV, Oriol A, Martínez-López J, Gutiérrez N, Teruel AI, de Paz R, García-Laraña J, Bengoechea E, Martín A, Mediavilla JD, Palomera L, de Arriba F, González Y, Hernández JM, Sureda A, Bello JL, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, García-Sanz R, Cibeira MT, Ramos ML, Vidriales MB, Paiva B, Montalbán MA, Lahuerta JJ, Bladé J, Miguel JF. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol. 2010 Oct;11(10):934-41. Epub 2010 Aug 23. link to original article contains verified protocol PubMed
- Update: Mateos MV, Oriol A, Martínez-López J, Teruel AI, López de la Guía A, López J, Bengoechea E, Pérez M, Martínez R, Palomera L, de Arriba F, González Y, Hernández JM, Granell M, Bello JL, Bargay J, Peñalver FJ, Martín-Mateos ML, Paiva B, Montalbán MA, Bladé J, Lahuerta JJ, San-Miguel JF. Update of the GEM2005 trial comparing VMP/VTP as induction in elderly multiple myeloma patients: do we still need alkylators? Blood. 2014 Aug 7. [Epub ahead of print] link to original article contains verified protocol PubMed
- Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R, Gentili S, Patriarca F, Nozzoli C, Levi A, Guglielmelli T, Benevolo G, Callea V, Rizzo V, Cangialosi C, Musto P, De Rosa L, Liberati AM, Grasso M, Falcone AP, Evangelista A, Cavo M, Gaidano G, Boccadoro M, Palumbo A. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood. 2010 Dec 2;116(23):4745-53. Epub 2010 Aug 31. link to original article contains verified protocol PubMed
- Palumbo A, Bringhen S, Rossi D, Cavalli M, Larocca A, Ria R, Offidani M, Patriarca F, Nozzoli C, Guglielmelli T, Benevolo G, Callea V, Baldini L, Morabito F, Grasso M, Leonardi G, Rizzo M, Falcone AP, Gottardi D, Montefusco V, Musto P, Petrucci MT, Ciccone G, Boccadoro M. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol. 2010 Dec 1;28(34):5101-9. Epub 2010 Oct 12. link to original article contains verified protocol PubMed
- Subset analysis: Morabito F, Gentile M, Mazzone C, Rossi D, Di Raimondo F, Bringhen S, Ria R, Offidani M, Patriarca F, Nozzoli C, Petrucci MT, Benevolo G, Vincelli I, Guglielmelli T, Grasso M, Marasca R, Baldini L, Montefusco V, Musto P, Cascavilla N, Majolino I, Musolino C, Cavo M, Boccadoro M, Palumbo A. Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment. Blood. 2011 Nov 24;118(22):5759-66. Epub 2011 Sep 27. link to original article PubMed
- Update: Palumbo A, Bringhen S, Larocca A, Rossi D, Di Raimondo F, Magarotto V, Patriarca F, Levi A, Benevolo G, Vincelli ID, Grasso M, Franceschini L, Gottardi D, Zambello R, Montefusco V, Falcone AP, Omedé P, Marasca R, Morabito F, Mina R, Guglielmelli T, Nozzoli C, Passera R, Gaidano G, Offidani M, Ria R, Petrucci MT, Musto P, Boccadoro M, Cavo M. Bortezomib-Melphalan-Prednisone-Thalidomide Followed by Maintenance With Bortezomib-Thalidomide Compared With Bortezomib-Melphalan-Prednisone for Initial Treatment of Multiple Myeloma: Updated Follow-Up and Improved Survival. J Clin Oncol. 2014 Mar 1;32(7):634-40. Epub 2014 Jan 21. link to original article contains verified protocol PubMed
- Niesvizky R, Flinn IW, Rifkin R, Gabrail N, Charu V, Clowney B, Essell J, Gaffar Y, Warr T, Neuwirth R, Zhu Y, Elliott J, Esseltine DL, Niculescu L, Reeves J. Community-Based Phase IIIB Trial of Three UPFRONT Bortezomib-Based Myeloma Regimens. J Clin Oncol. 2015 Jun 8. [Epub ahead of print] link to original article contains verified protocol PubMed
VMPT-VT
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VMPT-VT: Velcade (Bortezomib), Melphalan, Prednisone, Thalidomide, Velcade (Bortezomib) maintenance, Thalidomide maintenance
Regimen #1
Study | Evidence | Comparator | Efficacy |
Palumbo et al. 2010 | Phase III | VMP | Seems to have superior OS |
- Bortezomib (Velcade) as follows:
- Cycles 1 to 4: 1.3 mg/m2 IV bolus once per day on days 1, 4, 8, 11, 22, 25, 29, 32
- Cycles 5 to 9: 1.3 mg/m2 IV bolus once per day on days 1, 8, 22, 29
- Melphalan (Alkeran) 9 mg/m2 PO once per day on days 1 to 4
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 4
- Thalidomide (Thalomid) 50 mg PO once per day on days 1 to 42
42-day cycles x 9 cycles
Treatment followed by VT maintenance therapy.
Regimen #2
Study | Evidence | Comparator | Efficacy |
Palumbo et al. 2010 | Phase III | VMP | Seems to have superior OS |
This represents a mid-protocol change (in 2007) where cycle length was decreased from 6 to 5 weeks and bortezomib was changed to weekly dosing.
- Bortezomib (Velcade) 1.3 mg/m2 IV bolus once per day on days 1, 8, 15, 22
- Melphalan (Alkeran) 9 mg/m2 PO once per day on days 1 to 4
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 4
- Thalidomide (Thalomid) 50 mg PO once per day on days 1 to 42
35-day cycles x 9 cycles
Treatment followed by VT maintenance therapy.
References
- Palumbo A, Bringhen S, Rossi D, Cavalli M, Larocca A, Ria R, Offidani M, Patriarca F, Nozzoli C, Guglielmelli T, Benevolo G, Callea V, Baldini L, Morabito F, Grasso M, Leonardi G, Rizzo M, Falcone AP, Gottardi D, Montefusco V, Musto P, Petrucci MT, Ciccone G, Boccadoro M. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol. 2010 Dec 1;28(34):5101-9. Epub 2010 Oct 12. link to original article contains verified protocol PubMed
- Post-hoc analysis: Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R, Gentili S, Patriarca F, Nozzoli C, Levi A, Guglielmelli T, Benevolo G, Callea V, Rizzo V, Cangialosi C, Musto P, De Rosa L, Liberati AM, Grasso M, Falcone AP, Evangelista A, Cavo M, Gaidano G, Boccadoro M, Palumbo A. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood. 2010 Dec 2;116(23):4745-53. Epub 2010 Aug 31. link to original article contains verified protocol PubMed
- Subset analysis: Morabito F, Gentile M, Mazzone C, Rossi D, Di Raimondo F, Bringhen S, Ria R, Offidani M, Patriarca F, Nozzoli C, Petrucci MT, Benevolo G, Vincelli I, Guglielmelli T, Grasso M, Marasca R, Baldini L, Montefusco V, Musto P, Cascavilla N, Majolino I, Musolino C, Cavo M, Boccadoro M, Palumbo A. Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment. Blood. 2011 Nov 24;118(22):5759-66. Epub 2011 Sep 27. link to original article PubMed
- Update: Palumbo A, Bringhen S, Larocca A, Rossi D, Di Raimondo F, Magarotto V, Patriarca F, Levi A, Benevolo G, Vincelli ID, Grasso M, Franceschini L, Gottardi D, Zambello R, Montefusco V, Falcone AP, Omedé P, Marasca R, Morabito F, Mina R, Guglielmelli T, Nozzoli C, Passera R, Gaidano G, Offidani M, Ria R, Petrucci MT, Musto P, Boccadoro M, Cavo M. Bortezomib-Melphalan-Prednisone-Thalidomide Followed by Maintenance With Bortezomib-Thalidomide Compared With Bortezomib-Melphalan-Prednisone for Initial Treatment of Multiple Myeloma: Updated Follow-Up and Improved Survival. J Clin Oncol. 2014 Mar 1;32(7):634-40. Epub 2014 Jan 21. link to original article contains verified protocol PubMed
Consolidation and/or maintenance after upfront therapy
Bortezomib (Velcade)
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Regimen #1
Study | Evidence |
Niesvizky et al. 2015 (UPFRONT) | Non-randomized |
Treatment preceded by VD x 8 versus VMP x 8 versus VTD x 8. All patients received the same maintenance program:
- Bortezomib (Velcade) 1.6 mg/m2 IV once per day on days 1, 8, 15, 22
35-day cycle x 5 cycles
Regimen #2
Study | Evidence | Comparator | Efficacy |
Mellqvist et al. 2013 | Phase III | Observation | Might have superior PFS |
This trial only included bortezomib-naive patients; induction regimen was not specified but the majority received Cy-Dex. All patients underwent autologous stem cell transplant at least 3 months prior to starting maintenance.
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
21-day cycle x 2 cycles, then:
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
Supportive medications:
- Bisphosphonates were administered "according to national guidelines."
28-day cycle x 4 cycles
Regimen #3
Study | Evidence | Comparator | Efficacy |
Sonneveld et al. 2012 (HOVON-65/GMMG-HD4) | Phase III | Thalidomide | Seems to have superior OS |
Observed efficacy is for induction PAD -> transplant -> maintenance bortezomib compared with induction VAD -> transplant -> maintenance thalidomide. Treatment started 4 weeks after single autologous stem cell transplant (HOVON-65) or tandem autologous stem cell transplant (GMMG-HD4).
- Bortezomib (Velcade) 1.3 mg/m2 IV once on day 1
14-day cycle x 2 years
References
- Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012 Aug 20;30(24):2946-55. Epub 2012 Jul 16. link to original article contains verified protocol PubMed
- Mellqvist UH, Gimsing P, Hjertner O, Lenhoff S, Laane E, Remes K, Steingrimsdottir H, Abildgaard N, Ahlberg L, Blimark C, Dahl IM, Forsberg K, Gedde-Dahl T, Gregersen H, Gruber A, Guldbrandsen N, Haukås E, Carlson K, Kvam AK, Nahi H, Lindås R, Andersen NF, Turesson I, Waage A, Westin J; Nordic Myeloma Study Group. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial. Blood. 2013 Jun 6;121(23):4647-54. Epub 2013 Apr 24. link to original article contains verified protocol PubMed
- Niesvizky R, Flinn IW, Rifkin R, Gabrail N, Charu V, Clowney B, Essell J, Gaffar Y, Warr T, Neuwirth R, Zhu Y, Elliott J, Esseltine DL, Niculescu L, Reeves J. Community-Based Phase IIIB Trial of Three UPFRONT Bortezomib-Based Myeloma Regimens. J Clin Oncol. 2015 Jun 8. [Epub ahead of print] link to original article contains verified protocol PubMed
Carfilzomib (Kyprolis)
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Regimen
Study | Evidence |
Bringhen et al. 2014 | Phase II |
Treatment preceded by CCyd x 9.
- Carfilzomib (Kyprolis) 36 mg/m2 IV once per day on days 1, 2, 15, 16
28-day cycles, given until progression of disease or unacceptable toxicity
References
- Bringhen S, Petrucci MT, Larocca A, Conticello C, Rossi D, Magarotto V, Musto P, Boccadifuoco L, Offidani M, Omedé P, Gentilini F, Ciccone G, Benevolo G, Genuardi M, Montefusco V, Oliva S, Caravita T, Tacchetti P, Boccadoro M, Sonneveld P, Palumbo A. Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study. Blood. 2014 Jul 3;124(1):63-9. Epub 2014 May 22. link to original article contains verified protocol PubMed
DCEP
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DCEP: Dexamethasone, Cyclophosphamide, Etoposide, Platinol (Cisplatin)
Regimen
Study | Evidence | Comparator | Efficacy |
Harousseau et al. 2010 (IFM 2005-01) | Phase III | Autologous stem cell transplant | Seems not superior |
Treatment preceded by VD x 4 verus VAD x 4.
- Dexamethasone (Decadron) 40 mg once per day on days 1 to 4
- Cyclophosphamide (Cytoxan) 400 mg/m2/day (total dose per cycle: 1600 mg/m2) IV continuous infusion over 4 days on days 1 to 4
- Etoposide (Vepesid) 40 mg/m2/day (total dose per cycle: 160 mg/m2) IV continuous infusion over 4 days on days 1 to 4
- Cisplatin (Platinol) 15 mg/m2/day (total dose per cycle: 60 mg/m2) IV continuous infusion over 4 days on days 1 to 4
28-day cycles x 2 cycles
All patients then proceeded to receive autologous stem cell transplant.
References
- Harousseau JL, Attal M, Avet-Loiseau H, Marit G, Caillot D, Mohty M, Lenain P, Hulin C, Facon T, Casassus P, Michallet M, Maisonneuve H, Benboubker L, Maloisel F, Petillon MO, Webb I, Mathiot C, Moreau P. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol. 2010 Oct 20;28(30):4621-9. Epub 2010 Sep 7. link to original article contains verified protocol PubMed
Dexamethasone (Decadron)
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Regimen
Study | Evidence |
Cavo et al. 2010 | Non-randomized |
Treatment preceded by VTD consolidation therapy.
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
Supportive medications:
- Acyclovir (Zovirax) prophylaxis recommended
28-day cycles until progression, relapse, or undue toxicity
References
- Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, Di Raimondo F, Crippa C, Zamagni E, Palumbo A, Offidani M, Corradini P, Narni F, Spadano A, Pescosta N, Deliliers GL, Ledda A, Cellini C, Caravita T, Tosi P, Baccarani M; GIMEMA Italian Myeloma Network. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010 Dec 18;376(9758):2075-85. Epub 2010 Dec 9. link to original article contains protocol PubMed
- Update: Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A; GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto) Italian Myeloma Network. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2012 Jul 5;120(1):9-19. Epub 2012 Apr 12. link to original article contains verified protocol PubMed
KTd
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KTd: Kyprolis (Carfilzomib), Thalidomide, dexamethasone
Regimen
Study | Evidence |
Sonneveld et al. 2014 | Phase II |
Treatment preceded by high-dose melphalan with stem cell rescue.
- Carfilzomib (Kyprolis) as follows:
- Cohort 1: 27 mg/m2 IV once per day on days 1, 2, 8, 9, 15, 16
- Cohort 2: 36 mg/m2 IV once per day on days 1, 2, 8, 9, 15, 16
- Thalidomide (Thalomid) 50 mg PO once per day
- Dexamethasone (Decadron) 20 mg PO once per day on days 1, 8, 15, 22
28-day cycle x 4 cycles
References
- Sonneveld P, Asselbergs E, Zweegman S, van der Holt B, Kersten MJ, Vellenga E, van Marwijk-Kooy M, Broyl A, de Weerdt O, Lonergan S, Palumbo A, Lokhorst H. Phase 2 study of carfilzomib, thalidomide and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma. Blood. 2015 Jan 15;125(3):449-56. Epub 2014 Nov 14. link to original article contains verified protocol PubMed
Lenalidomide (Revlimid)
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Regimen #1
Study | Evidence | Comparator | Efficacy |
Palumbo et al. 2007 | Phase II | ||
Palumbo et al. 2012 (MM-015) | Phase III | Placebo | Superior PFS |
Palumbo et al. 2014 (RV-MM-PI-209) | Phase III | Observation | Superior PFS |
Treatment in Palumbo et al. 2007 and MM-015 was preceded by MPR x 9. Treatment in RV-MM-PI-209 was preceded by autologous stem cell transplant versus MPR consolidation.
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
Supportive medications (varies depending on reference):
- Palumbo et al. 2012: Aspirin 75 to 100 mg PO once per day as thromboprophylaxis
- Palumbo et al. 2007: Ciprofloxacin (Cipro) 500 mg PO BID and Aspirin 100 mg PO once per day
28-day cycles, given until progression or intolerable toxicity
Regimen #2
Study | Evidence | Comparator |
Attal et al. 2012 (IFM 2005-02) | Phase III | Placebo |
Consolidation
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
28-day cycle x 2 cycles, then
Maintenance
- Lenalidomide (Revlimid) 10 mg PO once per day x 3 months, then increased to 15 mg PO once per day if tolerated
Supportive medications:
- "Thromboprophylaxis was not used"
Given until progression of disease or unacceptable toxicity, or patient choice
Regimen #3
Study | Evidence | Comparator |
McCarthy et al. 2012 (CALGB 100104) | Phase III | Placebo |
Patients started therapy 100 to 120 days after autologous hematopoietic cell transplant (AHCT).
- Lenalidomide (Revlimid) 20 mg PO once per day; after 3 months, dose may be increased to 30 mg PO once per day if the patient's ANC remains at least 1000/uL and platelet count is at least 75,000/uL
- Dose adjustments can be found in the paper's supplementary appendix
Supportive medications:
- Patients at high risk of deep venous thrombosis (DVT) or pulmonary embolism (PE) received Aspirin, low molecular weight heparin, or Warfarin (Coumadin) unless contraindicated. High risk patients were defined as people with: history of diabetes, coronary artery disease, "DVT/PE, significant family history, performance status = 2, smoking history, use of oral contraceptives, and[/or] concurrent use of epoetin."
Given until progression of disease or unacceptable toxicity
Regimen #4
Study | Evidence |
Palumbo et al. 2010 | Phase II |
See First-line regimens: VDD; PAD: Palumbo et al. 2010 for details about the induction therapy portion of this regimen.
Consolidation
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
- Prednisone (Sterapred) 50 mg PO once every other day
28-day cycle x 4 cycles, then proceed to maintenance therapy
Maintenance
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
28-day cycles, given until relapsed disease
Supportive medications:
- Aspirin 100 mg PO once per day during Lenalidomide (Revlimid) treatment
Regimen #5, limited duration
Study | Evidence |
Roussel et al. 2014 | Phase II |
Treatment preceded by RVD x 2.
- Lenalidomide (Revlimid) 10 mg PO once per day, escalated to 15 mg PO once per day after 3 months, if tolerated.
12-month course
References
- Palumbo A, Falco P, Corradini P, Falcone A, Di Raimondo F, Giuliani N, Crippa C, Ciccone G, Omedè P, Ambrosini MT, Gay F, Bringhen S, Musto P, Foà R, Knight R, Zeldis JB, Boccadoro M, Petrucci MT; GIMEMA--Italian Multiple Myeloma Network. Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report from the GIMEMA--Italian Multiple Myeloma Network. J Clin Oncol. 2007 Oct 1;25(28):4459-65. Epub 2007 Sep 4. link to original article contains verified protocol PubMed
- Palumbo A, Gay F, Falco P, Crippa C, Montefusco V, Patriarca F, Rossini F, Caltagirone S, Benevolo G, Pescosta N, Guglielmelli T, Bringhen S, Offidani M, Giuliani N, Petrucci MT, Musto P, Liberati AM, Rossi G, Corradini P, Boccadoro M. Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients. J Clin Oncol. 2010 Feb 10;28(5):800-7. Epub 2010 Jan 4. Erratum in: J Clin Oncol. 2010 May 1;28(13):2314. link to original article contains verified protocol PubMed
- Update: Gay F, Magarotto V, Crippa C, Pescosta N, Guglielmelli T, Cavallo F, Pezzatti S, Ferrari S, Liberati AM, Oliva S, Patriarca F, Offidani M, Omedé P, Montefusco V, Petrucci MT, Giuliani N, Passera R, Pietrantuono G, Boccadoro M, Corradini P, Palumbo A. Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results. Blood. 2013 Aug 22;122(8):1376-83. Epub 2013 Jun 17. link to original article contains protocol PubMed
- McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, Giralt S, Stadtmauer EA, Weisdorf DJ, Vij R, Moreb JS, Callander NS, Van Besien K, Gentile T, Isola L, Maziarz RT, Gabriel DA, Bashey A, Landau H, Martin T, Qazilbash MH, Levitan D, McClune B, Schlossman R, Hars V, Postiglione J, Jiang C, Bennett E, Barry S, Bressler L, Kelly M, Seiler M, Rosenbaum C, Hari P, Pasquini MC, Horowitz MM, Shea TC, Devine SM, Anderson KC, Linker C. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012 May 10;366(19):1770-81. link to original article link to supplementary appendix contains verified protocol PubMed
- Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, Stoppa AM, Hulin C, Benboubker L, Garderet L, Decaux O, Leyvraz S, Vekemans MC, Voillat L, Michallet M, Pegourie B, Dumontet C, Roussel M, Leleu X, Mathiot C, Payen C, Avet-Loiseau H, Harousseau JL; IFM Investigators. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012 May 10;366(19):1782-91. link to original article contains verified protocol PubMed
- Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, Gisslinger H, Wiktor-Jedrzejczak W, Zodelava M, Weisel K, Cascavilla N, Iosava G, Cavo M, Kloczko J, Bladé J, Beksac M, Spicka I, Plesner T, Radke J, Langer C, Ben Yehuda D, Corso A, Herbein L, Yu Z, Mei J, Jacques C, Dimopoulos MA; MM-015 Investigators. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012 May 10;366(19):1759-69. Erratum in: N Engl J Med. 2012 Jul 19;367(3):285. link to original article contains verified protocol PubMed
- Roussel M, Lauwers-Cances V, Robillard N, Hulin C, Leleu X, Benboubker L, Marit G, Moreau P, Pegourie B, Caillot D, Fruchart C, Stoppa AM, Gentil C, Wuilleme S, Huynh A, Hebraud B, Corre J, Chretien ML, Facon T, Avet-Loiseau H, Attal M. Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myélome. J Clin Oncol. 2014 Sep 1;32(25):2712-7. Epub 2014 Jul 14. link to original article contains verified protocol PubMed
- Palumbo A, Cavallo F, Gay F, Di Raimondo F, Ben Yehuda D, Petrucci MT, Pezzatti S, Caravita T, Cerrato C, Ribakovsky E, Genuardi M, Cafro A, Marcatti M, Catalano L, Offidani M, Carella AM, Zamagni E, Patriarca F, Musto P, Evangelista A, Ciccone G, Omedé P, Crippa C, Corradini P, Nagler A, Boccadoro M, Cavo M. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014 Sep 4;371(10):895-905. link to original article contains verified protocol PubMed
Melphalan (Alkeran)
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Regimen
Study | Evidence |
McElwain, Powles 1983 | Pilot Study |
Note that this is highly obsolete but included for historical interest. Stem cell rescue was NOT used.
- Melphalan (Alkeran) 100 to 140 mg/m2 IV once
References
- McElwain TJ, Powles RL. High-dose intravenous melphalan for plasma-cell leukaemia and myeloma. Lancet. 1983 Oct 8;2(8354):822-4. link to original article PubMed
Melphalan -> autologous stem cell transplant
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Note that this is very incomplete and will be filled in over time.
Regimen
Study | Evidence | Comparator | Efficacy |
Moreau et al. 2011 (IFM2007-02) | Non-randomized | ||
Sonneveld et al. 2012 (HOVON-65/GMMG-HD4) | Non-randomized | ||
Roussel et al. 2014 | Phase II | ||
Palumbo et al. 2014 (RV-MM-PI-209) | Phase III | MPR consolidation | Seems to have superior OS |
Sonneveld et al. 2014 | Phase II |
Treatment in IFM2007-02 was preceded by vtD x 4 versus VD x 4. Treatment in HOVON-65 was preceded by PAD x 3 versus VAD x 3. Treatment in Roussel et al. 2014 was preceded by RVD x 3. Treatment in RV-MM-PI-209 was preceded by VD x 4. Treatment in Sonneveld et al. 2014 was preceded by KTd induction x 4.
- Melphalan (Alkeran) 200 mg/m2 IV on day -2
Stem cells re-infused on day 0
Patients in HOVON-65 proceeded to receive bortezomib maintenance if they were induced with PAD versus thalidomide maintenance if they were induced with VAD. Patients in Roussel et al. 2014 proceeded to receive RVD consolidation. Patients in RV-MM-PI-209 proceeded to receive lenalidomide maintenance versus no further treatment. Patients in Sonneveld et al. 2014 proceeded to receive KTd consolidation x 4.
References
- Moreau P, Avet-Loiseau H, Facon T, Attal M, Tiab M, Hulin C, Doyen C, Garderet L, Randriamalala E, Araujo C, Lepeu G, Marit G, Caillot D, Escoffre M, Lioure B, Benboubker L, Pégourié B, Kolb B, Stoppa AM, Fuzibet JG, Decaux O, Dib M, Berthou C, Chaleteix C, Sebban C, Traullé C, Fontan J, Wetterwald M, Lenain P, Mathiot C, Harousseau JL. Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus dexamethasone as induction treatment before autologous stem cell transplantation in newly diagnosed multiple myeloma. Blood. 2011 Nov 24;118(22):5752-8. Epub 2011 Aug 17. link to original article contains verified protocol PubMed
- Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012 Aug 20;30(24):2946-55. Epub 2012 Jul 16. link to original article contains verified protocol PubMed
- Roussel M, Lauwers-Cances V, Robillard N, Hulin C, Leleu X, Benboubker L, Marit G, Moreau P, Pegourie B, Caillot D, Fruchart C, Stoppa AM, Gentil C, Wuilleme S, Huynh A, Hebraud B, Corre J, Chretien ML, Facon T, Avet-Loiseau H, Attal M. Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myélome. J Clin Oncol. 2014 Sep 1;32(25):2712-7. Epub 2014 Jul 14. link to original article contains verified protocol PubMed
- Palumbo A, Cavallo F, Gay F, Di Raimondo F, Ben Yehuda D, Petrucci MT, Pezzatti S, Caravita T, Cerrato C, Ribakovsky E, Genuardi M, Cafro A, Marcatti M, Catalano L, Offidani M, Carella AM, Zamagni E, Patriarca F, Musto P, Evangelista A, Ciccone G, Omedé P, Crippa C, Corradini P, Nagler A, Boccadoro M, Cavo M. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014 Sep 4;371(10):895-905. link to original article contains verified protocol PubMed
- Sonneveld P, Asselbergs E, Zweegman S, van der Holt B, Kersten MJ, Vellenga E, van Marwijk-Kooy M, Broyl A, de Weerdt O, Lonergan S, Palumbo A, Lokhorst H. Phase 2 study of carfilzomib, thalidomide and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma. Blood. 2015 Jan 15;125(3):449-56. Epub 2014 Nov 14. link to original article contains verified protocol PubMed
Melphalan + TBI -> autologous stem cell transplant
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Regimen
Study | Evidence | Comparator | Efficacy |
Attal et al. 1996 | Phase III | VMCP/BVAP x 18 | Seems to have superior OS |
Treatment preceded by 4 to 6 alternating cycles of VMCP and BVAP.
- Melphalan (Alkeran) 140 mg/m2 IV (day not specified)
- Total-body irradiation in 2 Gy fractions once per day x 4 = total dose of 8 Gy, without lung shielding
One course; relative date of stem cell re-infusion not specified
Followed by maintenance interferon alfa.
References
- Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med. 1996 Jul 11;335(2):91-7. link to original article contains verified protocol PubMed
Observation
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Regimen
Study | Evidence | Comparator | Efficacy |
Attal et al. 2012 (IFM 2005-02) | Phase III | Lenalidomide | |
McCarthy et al. 2012 (CALGB 100104) | Phase III | Lenalidomide | |
Stewart et al. 2013 (NCICCTG Myeloma 10 Trial) | Phase III | Thalidomide & Prednisone | |
Mellqvist et al. 2013 | Phase III | Bortezomib | Might have inferior PFS |
Palumbo et al. 2014 (RV-MM-PI-209) | Phase III | Lenalidomide |
No treatment or placebo; used as a comparator arm.
References
- Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, Stoppa AM, Hulin C, Benboubker L, Garderet L, Decaux O, Leyvraz S, Vekemans MC, Voillat L, Michallet M, Pegourie B, Dumontet C, Roussel M, Leleu X, Mathiot C, Payen C, Avet-Loiseau H, Harousseau JL; IFM Investigators. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012 May 10;366(19):1782-91. link to original article contains verified protocol PubMed
- McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, Giralt S, Stadtmauer EA, Weisdorf DJ, Vij R, Moreb JS, Callander NS, Van Besien K, Gentile T, Isola L, Maziarz RT, Gabriel DA, Bashey A, Landau H, Martin T, Qazilbash MH, Levitan D, McClune B, Schlossman R, Hars V, Postiglione J, Jiang C, Bennett E, Barry S, Bressler L, Kelly M, Seiler M, Rosenbaum C, Hari P, Pasquini MC, Horowitz MM, Shea TC, Devine SM, Anderson KC, Linker C. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012 May 10;366(19):1770-81. link to original article link to supplementary appendix contains verified protocol PubMed
- Stewart AK, Trudel S, Bahlis NJ, White D, Sabry W, Belch A, Reiman T, Roy J, Shustik C, Kovacs MJ, Rubinger M, Cantin G, Song K, Tompkins KA, Marcellus DC, Lacy MQ, Sussman J, Reece D, Brundage M, Harnett EL, Shepherd L, Chapman JA, Meyer RM. A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial. Blood. 2013 Feb 28;121(9):1517-23. Epub 2013 Jan 7. link to original article contains verified protocol PubMed
- Mellqvist UH, Gimsing P, Hjertner O, Lenhoff S, Laane E, Remes K, Steingrimsdottir H, Abildgaard N, Ahlberg L, Blimark C, Dahl IM, Forsberg K, Gedde-Dahl T, Gregersen H, Gruber A, Guldbrandsen N, Haukås E, Carlson K, Kvam AK, Nahi H, Lindås R, Andersen NF, Turesson I, Waage A, Westin J; Nordic Myeloma Study Group. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial. Blood. 2013 Jun 6;121(23):4647-54. Epub 2013 Apr 24. link to original article contains verified protocol PubMed
- Palumbo A, Cavallo F, Gay F, Di Raimondo F, Ben Yehuda D, Petrucci MT, Pezzatti S, Caravita T, Cerrato C, Ribakovsky E, Genuardi M, Cafro A, Marcatti M, Catalano L, Offidani M, Carella AM, Zamagni E, Patriarca F, Musto P, Evangelista A, Ciccone G, Omedé P, Crippa C, Corradini P, Nagler A, Boccadoro M, Cavo M. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014 Sep 4;371(10):895-905. link to original article contains verified protocol PubMed
Prednisone
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Regimen #1
Study | Evidence | Comparator |
Berenson et al. 2002 (SWOG 9210) | Phase III | Low-dose prednisone |
Treatment preceded by VAD-P or VAD-P/Q.
Patients with at least 50% regression in 6 months or 25% regression in 9 to 12 months of therapy were then started on maintenance therapy:
- Prednisone (Sterapred) 50 mg PO once every other day until disease progression
Regimen #2
Study | Evidence | Comparator |
Berenson et al. 2002 (SWOG 9210) | Phase III | High-dose prednisone |
Treatment preceded by VAD-P or VAD-P/Q.
Patients with at least 50% regression in 6 months or 25% regression in 9 to 12 months of therapy were then started on maintenance therapy:
- Prednisone (Sterapred) 10 mg PO once every other day until disease progression
References
- Berenson JR, Crowley JJ, Grogan TM, Zangmeister J, Briggs AD, Mills GM, Barlogie B, Salmon SE. Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients. Blood. 2002 May 1;99(9):3163-8. link to original article contains protocol PubMed
RVD
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RVD: Revlimid (Lenalidomide), Velcade (Bortezomib), Dexamethasone
Regimen #1
Study | Evidence |
Roussel et al. 2014 | Phase II |
Treatment preceded by autologous stem cell transplant. Two months after hematologic recovery, patients without progressive disease received:
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 14
- 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, 8, 15
Supportive medications:
- Low–molecular weight heparin (LMWH) for DVT prophylaxis
- Antiviral therapy with example valacyclovir given, for herpes zoster prevention
- Antibiotic prophylaxis with example amoxicillin given, for bacterial infections
21-day cycle x 2 cycles
Patients then proceeded to receive lenalidomide maintenance.
Regimen #2
Study | Evidence |
Richardson et al. 2010 | Phase II |
Treatment preceded by RVD x 4 to 8 cycles.
- Lenalidomide (Revlimid) 25 mg (or previously tolerated dose) PO once per day on days 1 to 14
- Bortezomib (Velcade) 1.3 mg/m2 (or previously tolerated dose) IV once per day on days 1 & 8
- Dexamethasone (Decadron) 20 mg (or previously tolerated dose) PO once per day on days 1, 2, 8, 9
Supportive medications:
- Aspirin 81 mg or 325 mg PO once per day
- Antiviral therapy, such as Acyclovir (Zovirax) 400 mg PO once per day
- Bisphosphonate
21-day cycles until progression or intolerance
References
- Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS, Avigan DE, Xie W, Ghobrial IM, Schlossman RL, Mazumder A, Munshi NC, Vesole DH, Joyce R, Kaufman JL, Doss D, Warren DL, Lunde LE, Kaster S, Delaney C, Hideshima T, Mitsiades CS, Knight R, Esseltine DL, Anderson KC. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010 Aug 5;116(5):679-86. Epub 2010 Apr 12. link to original article contains protocol PubMed
- Nooka AK, Kaufman JL, Muppidi S, Langston A, Heffner LT, Gleason C, Casbourne D, Saxe D, Boise LH, Lonial S. Consolidation and maintenance therapy with lenalidomide, bortezomib and dexamethasone (RVD) in high-risk myeloma patients. Leukemia. 2014 Mar;28(3):690-3. Epub 2013 Nov 13. link to original article PubMed
- Roussel M, Lauwers-Cances V, Robillard N, Hulin C, Leleu X, Benboubker L, Marit G, Moreau P, Pegourie B, Caillot D, Fruchart C, Stoppa AM, Gentil C, Wuilleme S, Huynh A, Hebraud B, Corre J, Chretien ML, Facon T, Avet-Loiseau H, Attal M. Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myélome. J Clin Oncol. 2014 Sep 1;32(25):2712-7. Epub 2014 Jul 14. link to original article contains verified protocol PubMed
Thalidomide (Thalomid)
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Regimen #1
Study | Evidence | Comparator | Efficacy |
Sonneveld et al. 2012 (HOVON-65/GMMG-HD4) | Phase III | Bortezomib | Seems to have inferior OS |
Observed efficacy is for induction PAD -> transplant -> maintenance bortezomib compared with induction VAD -> transplant -> maintenance thalidomide. Treatment preceded by single autologous stem cell transplant (HOVON-65) or tandem autologous stem cell transplant (GMMG-HD4).
- Thalidomide (Thalomid) 50 mg PO once per day
2 years, starting 4 weeks after autologous stem cell transplant
Regimen #2
Study | Evidence |
Palumbo et al. 2006 | Non-randomized |
Treatment preceded by MPT x 6.
- Thalidomide (Thalomid) 100 mg PO once per day
Continued until evidence of relapse or refractory disease
Regimen #3
Study | Evidence |
Wijermans et al. 2010 (HOVON 49) | Non-randomized |
Treatment preceded by MPT x 8.
- Thalidomide (Thalomid) 50 mg PO once per day
Supportive medications:
- Bisphosphonate use recommended with Pamidronate (Aredia) or Clodronate (Bonefos); "a maximum treatment period of 2 years was recommended in patients without active disease."
- During maintenance therapy, "low-dose Aspirin was advised"
Continued until progression
References
- Palumbo A, Bringhen S, Caravita T, Merla E, Capparella V, Callea V, Cangialosi C, Grasso M, Rossini F, Galli M, Catalano L, Zamagni E, Petrucci MT, De Stefano V, Ceccarelli M, Ambrosini MT, Avonto I, Falco P, Ciccone G, Liberati AM, Musto P, Boccadoro M; Italian Multiple Myeloma Network, GIMEMA. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet. 2006 Mar 11;367(9513):825-31. link to original article contains protocol PubMed
- Update: Palumbo A, Bringhen S, Liberati AM, Caravita T, Falcone A, Callea V, Montanaro M, Ria R, Capaldi A, Zambello R, Benevolo G, Derudas D, Dore F, Cavallo F, Gay F, Falco P, Ciccone G, Musto P, Cavo M, Boccadoro M. Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood. 2008 Oct 15;112(8):3107-14. Epub 2008 May 27. link to original article contains protocol PubMed
- **RETRACTED** Abdelkefi A, Ladeb S, Torjman L, Othman TB, Lakhal A, Romdhane NB, Omri HE, Elloumi M, Belaaj H, Jeddi R, Aissaouï L, Ksouri H, Hassen AB, Msadek F, Saad A, Hsaïri M, Boukef K, Amouri A, Louzir H, Dellagi K, Abdeladhim AB; Tunisian Multiple Myeloma Study Group. Single autologous stem-cell transplantation followed by maintenance therapy with thalidomide is superior to double autologous transplantation in multiple myeloma: results of a multicenter randomized clinical trial. Blood. 2008 Feb 15;111(4):1805-10. Epub 2007 Sep 17. link to original article contains verified protocol PubMed **RETRACTED**
- Wijermans P, Schaafsma M, Termorshuizen F, Ammerlaan R, Wittebol S, Sinnige H, Zweegman S, van Marwijk Kooy M, van der Griend R, Lokhorst H, Sonneveld P; Dutch-Belgium Cooperative Group HOVON. Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study. J Clin Oncol. 2010 Jul 1;28(19):3160-6. Epub 2010 Jun 1. link to original article contains verified protocol PubMed
- Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012 Aug 20;30(24):2946-55. Epub 2012 Jul 16. link to original article contains verified protocol PubMed
Thalidomide & Prednisone
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Regimen
Study | Evidence | Comparator | Efficacy | Toxicity |
Stewart et al. 2013 (NCICCTG Myeloma 10 Trial) | Phase III | Observation | Improved PFS | Decreased QOL |
Treatment preceded by autologous stem cell transplant.
- Thalidomide (Thalomid) 200 mg PO once per day
- Prednisone (Sterapred) 50 mg PO once every other day
Supportive Medications:
- "Bisphosphonates, histamine-2 blockers, and laxatives were recommended"
- "Anticoagulant and antiplatelet medications were not mandated"
Four years or until disease progression
References
- Stewart AK, Trudel S, Bahlis NJ, White D, Sabry W, Belch A, Reiman T, Roy J, Shustik C, Kovacs MJ, Rubinger M, Cantin G, Song K, Tompkins KA, Marcellus DC, Lacy MQ, Sussman J, Reece D, Brundage M, Harnett EL, Shepherd L, Chapman JA, Meyer RM. A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial. Blood. 2013 Feb 28;121(9):1517-23. Epub 2013 Jan 7. link to original article contains verified protocol PubMed
VT
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VT: Velcade (Bortezomib), Thalidomide
Regimen
Study | Evidence |
Palumbo et al. 2010 | Non-randomized |
Treatment preceded by VMPT x 9.
- Bortezomib (Velcade) 1.3 mg/m2 IV bolus once on day 1
- Thalidomide (Thalomid) 50 mg PO once per day on days 1 to 14
14-day cycles x 2 years or until disease progression or relapse
References
- Palumbo A, Bringhen S, Rossi D, Cavalli M, Larocca A, Ria R, Offidani M, Patriarca F, Nozzoli C, Guglielmelli T, Benevolo G, Callea V, Baldini L, Morabito F, Grasso M, Leonardi G, Rizzo M, Falcone AP, Gottardi D, Montefusco V, Musto P, Petrucci MT, Ciccone G, Boccadoro M. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol. 2010 Dec 1;28(34):5101-9. Epub 2010 Oct 12. link to original article contains verified protocol PubMed
- Post-hoc analysis: Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R, Gentili S, Patriarca F, Nozzoli C, Levi A, Guglielmelli T, Benevolo G, Callea V, Rizzo V, Cangialosi C, Musto P, De Rosa L, Liberati AM, Grasso M, Falcone AP, Evangelista A, Cavo M, Gaidano G, Boccadoro M, Palumbo A. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood. 2010 Dec 2;116(23):4745-53. Epub 2010 Aug 31. link to original article contains verified protocol PubMed
- Subset analysis: Morabito F, Gentile M, Mazzone C, Rossi D, Di Raimondo F, Bringhen S, Ria R, Offidani M, Patriarca F, Nozzoli C, Petrucci MT, Benevolo G, Vincelli I, Guglielmelli T, Grasso M, Marasca R, Baldini L, Montefusco V, Musto P, Cascavilla N, Majolino I, Musolino C, Cavo M, Boccadoro M, Palumbo A. Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment. Blood. 2011 Nov 24;118(22):5759-66. Epub 2011 Sep 27. link to original article PubMed
- Update: Palumbo A, Bringhen S, Larocca A, Rossi D, Di Raimondo F, Magarotto V, Patriarca F, Levi A, Benevolo G, Vincelli ID, Grasso M, Franceschini L, Gottardi D, Zambello R, Montefusco V, Falcone AP, Omedé P, Marasca R, Morabito F, Mina R, Guglielmelli T, Nozzoli C, Passera R, Gaidano G, Offidani M, Ria R, Petrucci MT, Musto P, Boccadoro M, Cavo M. Bortezomib-Melphalan-Prednisone-Thalidomide Followed by Maintenance With Bortezomib-Thalidomide Compared With Bortezomib-Melphalan-Prednisone for Initial Treatment of Multiple Myeloma: Updated Follow-Up and Improved Survival. J Clin Oncol. 2014 Mar 1;32(7):634-40. Epub 2014 Jan 21. link to original article contains verified protocol PubMed
VTD
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VTD: Velcade (bortezomib), Thalidomide, Dexamethasone
Regimen #1
Study | Evidence |
Cavo et al. 2010 | Non-randomized |
Treatment preceded by VTD induction therapy and tandem autologous stem cell transplant. VTD consolidation is to begin 3 months after the second transplant.
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
- Thalidomide (Thalomid) 100 mg PO once per day on days 1 to 35
- Dexamethasone (Decadron) 40 mg PO once per day on days 1, 2, 8, 9, 15, 16, 22, 23
Supportive medications:
- Acyclovir (Zovirax) prophylaxis recommended
35-day cycles x 2 cycles
Followed by dexamethasone maintenance therapy.
Regimen #2
Study | Evidence |
Ladetto et al. 2010 (GIMEMA VEL-03-096) | Phase II |
Patients had at least a very good partial response (VGPR) after autologous stem cell transplantation.
- Bortezomib (Velcade) 1.6 mg/m2 IV once per day on days 1, 8, 15, 22
- Thalidomide (Thalomid) 50 mg PO once per day, increased by 50 mg each week, up to a maximum of 200 mg PO once per day
- Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4, 8 to 11, 15 to 18
35-day cycles x 4 cycles
References
- Ladetto M, Pagliano G, Ferrero S, Cavallo F, Drandi D, Santo L, Crippa C, De Rosa L, Pregno P, Grasso M, Liberati AM, Caravita T, Pisani F, Guglielmelli T, Callea V, Musto P, Cangialosi C, Passera R, Boccadoro M, Palumbo A. Major tumor shrinking and persistent molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in patients with autografted myeloma. J Clin Oncol. 2010 Apr 20;28(12):2077-84. Epub 2010 Mar 22. link to original article contains verified protocol PubMed
- Update: Ferrero S, Ladetto M, Drandi D, Cavallo F, Genuardi E, Urbano M, Caltagirone S, Grasso M, Rossini F, Guglielmelli T, Cangialosi C, Liberati AM, Callea V, Carovita T, Crippa C, De Rosa L, Pisani F, Falcone AP, Pregno P, Oliva S, Terragna C, Musto P, Passera R, Boccadoro M, Palumbo A. Long-term results of the GIMEMA VEL-03-096 trial in MM patients receiving VTD consolidation after ASCT: MRD kinetics' impact on survival. Leukemia. 2014 Jul 16. [Epub ahead of print] link to original article PMID 25027515
- Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, Di Raimondo F, Crippa C, Zamagni E, Palumbo A, Offidani M, Corradini P, Narni F, Spadano A, Pescosta N, Deliliers GL, Ledda A, Cellini C, Caravita T, Tosi P, Baccarani M; GIMEMA Italian Myeloma Network. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010 Dec 18;376(9758):2075-85. Epub 2010 Dec 9. link to original article contains protocol PubMed
- Update: Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A; GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto) Italian Myeloma Network. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2012 Jul 5;120(1):9-19. Epub 2012 Apr 12. link to original article contains verified protocol PubMed
Relapsed/refractory
BBD
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BBD: Bendamustine, Bortezomib, Dexamethasone
Regimen
Study | Evidence |
Ludwig et al. 2013 | Phase II |
- Bendamustine (Treanda) 70 mg/m2 IV once per day on days 1 & 4
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Dexamethasone (Decadron) 20 mg (route not specified) once per day on days 1, 4, 8, 11
28-day cycle up to 8 cycles
References
- Ludwig H, Kasparu H, Leitgeb C, Rauch E, Linkesch W, Zojer N, Greil R, Seebacher A, Pour L, Weißmann A, Adam Z. Bendamustine-bortezomib-dexamethasone is an active and well tolerated regimen in patients with relapsed or refractory multiple myeloma. Blood. 2014 Feb 13;123(7):985-91. Epub 2013 Nov 13. link to original article contains verified protocol PubMed
BD, Bort-Dex
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BD: Bortezomib, Dexamethasone
Bort-Dex: Bortezomib, Dexamethasone
Regimen #1
Study | Evidence | Comparator | Efficacy |
San-Miguel et al. 2014 (PANORAMA1) | Phase III | Bortezomib, Dexamethasone, Panobinostat | Decreased PFS |
Phase 1
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Dexamethasone (Decadron) 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
21-day cycles x 8 cycles
Patients who had clinical benefit per the modified European Group for Blood and Marrow Transplantation [EBMT] criteria on day 1 of cycle 8 proceeded to phase 2 treatment:
Phase 2
- Bortezomib (Velcade) 1.3 mg/m2 IV once per week days 1, 8, 22, 29
- Dexamethasone (Decadron) 20 mg PO once per day on days 1, 2, 8, 9, 22, 23, 29, 30
6-week cycles x 4 cycles
Regimen #2
Study | Evidence | Comparator | Efficacy |
Hjorth et al. 2012 | Phase III | Thal-Dex | Equivalent PFS |
Dimopoulos et al. 2013 | Phase II |
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Dexamethasone (Decadron) 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
Supportive medications:
- "Antithrombotic prophylaxis and acyclovir prophylaxis were not mandatory according to the study protocol but used routinely in an increasing proportion of participating centers during the study period."
21-day cycles, to be continued until progression or best response, which would then be followed by 1 to 2 additional cycles
Regimen #3
Study | Evidence |
Fukushima et al. 2011 | Phase II |
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
- Dexamethasone (Decadron) 20 mg PO/IV once per day on days 1, 2, 8, 9, 15, 16, 22, 23
35-day cycles, to be continued until complete response, progression of disease, or severe adverse events
References
- Subgroup Analysis: Jagannath S, Richardson PG, Barlogie B, Berenson JR, Singhal S, Irwin D, Srkalovic G, Schenkein DP, Esseltine DL, Anderson KC; SUMMIT/CREST Investigators. Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone. Haematologica. 2006 Jul;91(7):929-34. link to original article contains protocol PubMed
- Fukushima T, Nakamura T, Iwao H, Nakajima A, Miki M, Sato T, Sakai T, Sawaki T, Fujita Y, Tanaka M, Masaki Y, Nakajima H, Motoo Y, Umehara H. Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or relapsed multiple myeloma: once-weekly administration of bortezomib may reduce the incidence of gastrointestinal adverse events. Anticancer Res. 2011 Jun;31(6):2297-302. link to original article contains verified protocol PubMed
- Hjorth M, Hjertner Ø, Knudsen LM, Gulbrandsen N, Holmberg E, Pedersen PT, Andersen NF, Andréasson B, Billström R, Carlson K, Carlsson MS, Flogegård M, Forsberg K, Gimsing P, Karlsson T, Linder O, Nahi H, Othzén A, Swedin A; Nordic Myeloma Study Group (NMSG). Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan refractory myeloma: a randomized study. Eur J Haematol. 2012 Jun;88(6):485-96. Epub 2012 Mar 30. link to original article contains verified protocol PubMed
- Dimopoulos MA, Beksac M, Benboubker L, Roddie H, Allietta N, Broer E, Couturier C, Mazier MA, Angermund R, Facon T. Phase 2 study of bortezomib-dexamethasone alone or with added cyclophosphamide or lenalidomide for sub-optimal response as second-line treatment for patients with multiple myeloma. Haematologica. 2013 Aug;98(8):1264-72. Epub 2013 May 28. link to original article contains verified protocol PubMed
- San-Miguel JF, Hungria VT, Yoon SS, Beksac M, Dimopoulos MA, Elghandour A, Jedrzejczak WW, Günther A, Nakorn TN, Siritanaratkul N, Corradini P, Chuncharunee S, Lee JJ, Schlossman RL, Shelekhova T, Yong K, Tan D, Numbenjapon T, Cavenagh JD, Hou J, LeBlanc R, Nahi H, Qiu L, Salwender H, Pulini S, Moreau P, Warzocha K, White D, Bladé J, Chen W, de la Rubia J, Gimsing P, Lonial S, Kaufman JL, Ocio EM, Veskovski L, Sohn SK, Wang MC, Lee JH, Einsele H, Sopala M, Corrado C, Bengoudifa BR, Binlich F, Richardson PG. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1195-206. link to original article contains verified protocol PubMed
Bortezomib, Dexamethasone, Panobinostat
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Regimen
Study | Evidence | Comparator | Efficacy |
Richardson et al. 2013 (PANORAMA 2) | Phase II | ||
San-Miguel et al. 2014 (PANORAMA1) | Phase III | Bortezomib & Dexamethasone | Increased PFS |
Phase 1
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
- Dexamethasone (Decadron) 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
- Panobinostat (Farydak) 20 mg PO once per day on days 1, 3, 5, 8, 10, 12
21-day cycles x 8 cycles
Patients who had clinical benefit per the modified European Group for Blood and Marrow Transplantation [EBMT] criteria on day 1 of cycle 8 proceeded to phase 2 treatment:
Phase 2
- Bortezomib (Velcade) 1.3 mg/m2 IV once per week days 1, 8, 22, 29
- Dexamethasone (Decadron) 20 mg PO once per day on days 1, 2, 8, 9, 22, 23, 29, 30
- Panobinostat (Farydak) 20 mg PO once per day on days 1, 3, 5, 8, 10, 12, 22, 24, 26, 29, 31, 33
6-week cycles
San-Miguel et al. 2014 (PANORAMA1) gave 4 cycles; Richardson et al. 2013 (PANORAMA 2) continued treatment until progression of disease, unacceptable toxicity, or death.
References
- Richardson PG, Schlossman RL, Alsina M, Weber DM, Coutre SE, Gasparetto C, Mukhopadhyay S, Ondovik MS, Khan M, Paley CS, Lonial S. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood. 2013 Oct 3;122(14):2331-7. link to original article contains verified protocol PubMed
- San-Miguel JF, Hungria VT, Yoon SS, Beksac M, Dimopoulos MA, Elghandour A, Jedrzejczak WW, Günther A, Nakorn TN, Siritanaratkul N, Corradini P, Chuncharunee S, Lee JJ, Schlossman RL, Shelekhova T, Yong K, Tan D, Numbenjapon T, Cavenagh JD, Hou J, LeBlanc R, Nahi H, Qiu L, Salwender H, Pulini S, Moreau P, Warzocha K, White D, Bladé J, Chen W, de la Rubia J, Gimsing P, Lonial S, Kaufman JL, Ocio EM, Veskovski L, Sohn SK, Wang MC, Lee JH, Einsele H, Sopala M, Corrado C, Bengoudifa BR, Binlich F, Richardson PG. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1195-206. link to original article contains verified protocol PubMed
BLD
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BLD: Bendamustine, Lenalidomide, Dexamethasone
Regimen
Study | Evidence |
Lentzsch et al. 2012 | Phase II |
This study involved dose escalation. Dosages listed are the determined maximally tolerated doses (MTD).
- Bendamustine (Treanda) 75 mg/m2 IV once per day on days 1 & 2
- Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 40 mg (no route specified) once per week
Supportive medications:
- Aspirin 325 mg PO once per day
- "Gastroprotectant" (H2-blocker or PPI)
28-day cycles x up to 8 cycles
References
- Lentzsch S, O'Sullivan A, Kennedy RC, Abbas M, Dai L, Pregja SL, Burt S, Boyiadzis M, Roodman GD, Mapara MY, Agha M, Waas J, Shuai Y, Normolle D, Zonder JA. Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study. Blood. 2012 May 17;119(20):4608-13. Epub 2012 Mar 26. link to original article contains verified protocol PubMed
Bortezomib (Velcade)
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Regimen #1
Study | Evidence | Comparator | |
Jagannath et al. 2004 (CREST) | Randomized Phase II | Low-dose Bortezomib +/- Dexamethasone | |
Moreau et al. 2011 (MMY-3021) | Phase III | Subcutaneous Bortezomib +/- Dexamethasone |
Moreau et al. 2011 allowed for up to 10 cycles of treatment.
- Bortezomib (Velcade) 1.3 mg/m2 IV bolus once per day on days 1, 4, 8, 11
- Patients with suboptimal response after cycle 4 (less than complete response (CR), without disease progression) could also receive, in addition to bortezomib: Dexamethasone (Decadron) 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
21-day cycle x 8 cycles
Regimen #2
Study | Evidence | Comparator |
Richardson et al. 2005 (APEX) | Phase III | High-dose dexamethasone |
- Bortezomib (Velcade) 1.3 mg/m2 IV bolus once per day on days 1, 4, 8, 11
21-day cycle x 8 cycles, then
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 8, 15, 22
35-day cycle x 3 cycles
Supportive medications:
- Bisphosphonate IV therapy once every 3 to 4 weeks unless contraindicated
Regimen #3, Subcutaneous Bortezomib +/- Dexamethasone
Study | Evidence | Comparator |
Moreau et al. 2011 (MMY-3021) | Phase III | Intravenous Bortezomib +/- Dexamethasone |
- Bortezomib (Velcade) 1.3 mg/m2 SC once per day on days 1, 4, 8, 11
- Subcutaneous injections are 2.5 mg/mL (3.5 mg bortezomib reconstituted in 1.4 mL NS)
- SC injections are in the thighs or abdomen, with injection sites rotated between proximal/distal right/left thigh and upper/lower right/left abdominal quadrants
- Patients with suboptimal response after cycle 4 (less than complete response (CR), without disease progression) could also receive, in addition to bortezomib: Dexamethasone (Decadron) 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
Supportive medications:
- Bisphosphonates "according to established guidelines"
21-day cycle x 8 to 10 cycles
Regimen #4
Study | Evidence | Comparator | |
Orlowski et al. 2007 | Phase III | Bortezomib & Doxorubicin liposomal | |
Dimopoulos et al. 2013 (VANTAGE 088) | Phase III | Bortezomib & Vorinostat |
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
21-day cycles until progression or intolerance
Regimen #5
Study | Evidence | Comparator |
Jagannath et al. 2004 (CREST) | Randomized Phase II | Bortezomib +/- Dexamethasone |
- Bortezomib (Velcade) 1 mg/m2 IV bolus once per day on days 1, 4, 8, 11
- Patients with suboptimal response after cycle 4 (less than complete response (CR), without disease progression) could also receive, in addition to bortezomib: Dexamethasone (Decadron) 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
21-day cycle x 8 cycles
Regimen #6
Study | Evidence |
Richardson et al. 2003 (SUMMIT) | Phase II |
- Bortezomib (Velcade) 1.3 mg/m2 IV bolus once per day on days 1, 4, 8, 11
21-day cycle x 8 cycles
References
- Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, Rajkumar SV, Srkalovic G, Alsina M, Alexanian R, Siegel D, Orlowski RZ, Kuter D, Limentani SA, Lee S, Hideshima T, Esseltine DL, Kauffman M, Adams J, Schenkein DP, Anderson KC. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003 Jun 26;348(26):2609-17. link to original article contains verified protocol PubMed
- Subgroup Analysis: Jagannath S, Richardson PG, Barlogie B, Berenson JR, Singhal S, Irwin D, Srkalovic G, Schenkein DP, Esseltine DL, Anderson KC; SUMMIT/CREST Investigators. Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone. Haematologica. 2006 Jul;91(7):929-34. link to original article contains protocol PubMed
- Jagannath S, Barlogie B, Berenson J, Siegel D, Irwin D, Richardson PG, Niesvizky R, Alexanian R, Limentani SA, Alsina M, Adams J, Kauffman M, Esseltine DL, Schenkein DP, Anderson KC. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol. 2004 Oct;127(2):165-72. link to original article contains verified protocol PubMed
- Subgroup Analysis: Jagannath S, Richardson PG, Barlogie B, Berenson JR, Singhal S, Irwin D, Srkalovic G, Schenkein DP, Esseltine DL, Anderson KC; SUMMIT/CREST Investigators. Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone. Haematologica. 2006 Jul;91(7):929-34. link to original article contains protocol PubMed
- Update: Jagannath S, Barlogie B, Berenson JR, Siegel DS, Irwin D, Richardson PG, Niesvizky R, Alexanian R, Limentani SA, Alsina M, Esseltine DL, Anderson KC. Updated survival analyses after prolonged follow-up of the phase 2, multicenter CREST study of bortezomib in relapsed or refractory multiple myeloma. Br J Haematol. 2008 Nov;143(4):537-40. Epub 2008 Sep 6. link to original article PubMed
- Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, San-Miguel JF, Bladé J, Boccadoro M, Cavenagh J, Dalton WS, Boral AL, Esseltine DL, Porter JB, Schenkein D, Anderson KC; Assessment of Proteasome Inhibition for Extending Remissions (APEX) Investigators. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005 Jun 16;352(24):2487-98. link to original article contains verified protocol PubMed
- Update: Richardson PG, Sonneveld P, Schuster M, Irwin D, Stadtmauer E, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, Miguel JS, Bladé J, Boccadoro M, Cavenagh J, Alsina M, Rajkumar SV, Lacy M, Jakubowiak A, Dalton W, Boral A, Esseltine DL, Schenkein D, Anderson KC. Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood. 2007 Nov 15;110(10):3557-60. Epub 2007 Aug 9. link to original article contains verified protocol PubMed
- Orlowski RZ, Nagler A, Sonneveld P, Bladé J, Hajek R, Spencer A, San Miguel J, Robak T, Dmoszynska A, Horvath N, Spicka I, Sutherland HJ, Suvorov AN, Zhuang SH, Parekh T, Xiu L, Yuan Z, Rackoff W, Harousseau JL. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol. 2007 Sep 1;25(25):3892-901. Epub 2007 Aug 6. link to original article contains verified protocol PubMed
- Mikhael JR, Belch AR, Prince HM, Lucio MN, Maiolino A, Corso A, Petrucci MT, Musto P, Komarnicki M, Stewart AK. High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma: results of a global phase 3b expanded access program. Br J Haematol. 2009 Jan;144(2):169-75. Epub 2008 Nov 19. link to original article contains protocol PubMed
- Moreau P, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, Grishunina M, Rekhtman G, Masliak Z, Robak T, Shubina A, Arnulf B, Kropff M, Cavet J, Esseltine DL, Feng H, Girgis S, van de Velde H, Deraedt W, Harousseau JL. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol. 2011 May;12(5):431 to 40. Epub 2011 Apr 18. link to original article contains verified protocol PubMed
- Update: Arnulf B, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, van de Velde H, Feng H, Cakana A, Deraedt W, Moreau P. Updated survival analysis of a randomized phase III study of subcutaneous versus intravenous bortezomib in patients with relapsed multiple myeloma. Haematologica. 2012 Dec;97(12):1925-8. Epub 2012 Jun 11. link to original article PubMed
- Subgroup analysis: Moreau P, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, Rekhtman G, Masliak Z, Robak P, Esseltine DL, Feng H, Deraedt W, van de Velde H, Arnulf B. Subcutaneous versus intravenous bortezomib in patients with relapsed multiple myeloma: subanalysis of patients with renal impairment in the phase III MMY-3021 study. Haematologica. 2015 May;100(5):e207-10. Epub 2015 Jan 16. link to original article PubMed
- Dimopoulos M, Siegel DS, Lonial S, Qi J, Hajek R, Facon T, Rosinol L, Williams C, Blacklock H, Goldschmidt H, Hungria V, Spencer A, Palumbo A, Graef T, Eid JE, Houp J, Sun L, Vuocolo S, Anderson KC. Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study. Lancet Oncol. 2013 Oct;14(11):1129-1140. Epub 2013 Sep 19. link to original article contains verified protocol PubMed
Bortezomib & Doxorubicin liposomal
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Regimen
Study | Evidence | Comparator |
Orlowski et al. 2007 | Phase III | Bortezomib |
- Bortezomib (Velcade) 1.3 mg/m2 IV bolus once per day on days 1, 4, 8, 11
- Doxorubicin liposomal (Doxil) 30 mg/m2 IV over at least 1 hour once on day 4, given after Bortezomib (Velcade)
Supportive medications:
- Bisphosphonates were used according to established guidelines
21-day cycle x up to 8 cycles
Treatment given until progression of disease, or unacceptable toxicity; treatment could be continued beyond 8 cycles if it was tolerated.
References
- Orlowski RZ, Nagler A, Sonneveld P, Bladé J, Hajek R, Spencer A, San Miguel J, Robak T, Dmoszynska A, Horvath N, Spicka I, Sutherland HJ, Suvorov AN, Zhuang SH, Parekh T, Xiu L, Yuan Z, Rackoff W, Harousseau JL. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol. 2007 Sep 1;25(25):3892-901. Epub 2007 Aug 6. link to original article contains verified protocol PubMed
Bortezomib & Vorinostat
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Regimen
Study | Evidence | Comparator |
Dimopoulos et al. 2013 (VANTAGE 088) | Phase III | Bortezomib |
- Bortezomib (Velcade) 1.3 mg/m2 IV bolus once per day on days 1, 4, 8, 11
- Vorinostat (Zolinza) 400 mg PO once per day on days 1 to 14
21-day cycles
References
- Dimopoulos M, Siegel DS, Lonial S, Qi J, Hajek R, Facon T, Rosinol L, Williams C, Blacklock H, Goldschmidt H, Hungria V, Spencer A, Palumbo A, Graef T, Eid JE, Houp J, Sun L, Vuocolo S, Anderson KC. Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study. Lancet Oncol. 2013 Oct;14(11):1129-1140. Epub 2013 Sep 19. link to original article contains verified protocol PubMed
Carfilzomib (Kyprolis)
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Regimen #1 "20/56 dosing"
Study | Evidence |
Lendvai et al. 2014 | Phase II |
- Carfilzomib (Kyprolis) as follows:
- Cycle 1: 20 mg/m2 IV over 30 minutes once on days 1 & 2, then 56 mg/m2 IV over 30 minutes on days 8, 9, 15, 16
- Cycle 2 onwards: 56 mg/m2 IV over 30 minutes once on days 1, 2, 8, 9, 15, 16
Supportive medications:
- Normal saline pre- and post-hydration, tapered over subsequent cycles (see text for details)
- Dexamethasone (Decadron) 8 mg (route not specified) mandated with each cycle 1 dose, then optional
- Palonosetron (Aloxi) 250 mcg (route not specified) mandated with each cycle 1 dose, then optional
- Acyclovir (Zovirax) 400 mg PO once per day
Regimen #2 "20/27 dosing"
Study | Evidence | ||
Vij et al. 2012 (PX-171-004) | Phase II | ||
Siegel et al. 2012 (PX-171-003-A1) | Phase II |
- Carfilzomib (Kyprolis) as follows:
- Cycle 1: 20 mg/m2 (body surface area capped at 2.2 m2) IV over 2 to 10 minutes once per day on days 1, 2, 8, 9, 15, 16
- Cycle 2 onwards: 27 mg/m2 (body surface area capped at 2.2 m2) IV over 2 to 10 minutes once per day on days 1, 2, 8, 9, 15, 16
- Note: Neither Vij et al. 2012 nor Siegel et al. 2012 specify that carfilzomib is capped at a body surface area of 2.2 m2, but the Carfilzomib (Kyprolis) package insert specifies that: "The dose is calculated using the patient’s actual body surface area at baseline. Patients with a body surface area greater than 2.2 m2 should receive a dose based upon a body surface area of 2.2 m2. Dose adjustments do not need to be made for weight changes of less than or equal to 20%."
Supportive medications:
- Dexamethasone (Decadron) 4 mg PO/IV before all doses in cycle 1 (Vij et al. 2012 also administered one dose of dexamethasone 4 mg before the first increased dose of carfilzomib 27 mg/m2). Restart dexamethasone premedication if patients experience infusion reactions: "fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina."
- "All patients were to receive oral and intravenous fluids before dosing to assure adequate hydration."
Dose Adjustments:
- "Carfilzomib was withheld for grade 3 or 4 hematologic or nonhematologic toxicities and resumed at reduced doses of 15 mg/m2 in cycle 1 or 20 mg/m2 in cycle 2 and above on resolution."
28-day cycles x up to 12 cycles, given until progression of disease or unacceptable toxicity
Regimen #3
Study | Evidence |
Jagannath et al. 2012 (PX-171-003-A0) | Phase II |
As described in the abstract, this variant does not include dose escalation or BSA capping.
- Carfilzomib (Kyprolis) 20 mg/m2 IV once per day on days 1, 2, 8, 9, 15, 16
28-day cycles x up to 12 cycles
Regimen #4 "15/20/27 dosing for renal impairment"
Study | Evidence |
Badros et al. 2013 (PX-171-005) | Phase II |
- Carfilzomib (Kyprolis) as follows:
- Cycle 1: 15 mg/m2 IV over 2 to 10 minutes once per day on days 1, 2, 8, 9, 15, 16
- Cycle 2: 20 mg/m2 IV over 2 to 10 minutes once per day on days 1, 2, 8, 9, 15, 16
- Cycle 3 onwards: 27 mg/m2 IV over 2 to 10 minutes once per day on days 1, 2, 8, 9, 15, 16
Supportive medications:
- Dexamethasone (Decadron) 4 mg (route not specified) before all doses in cycle 1. Continue dexamethasone premedication if patients experience "treatment-related fever, chills, and/or dyspnea."
- "All patients were "required to be well hydrated."
28-day cycle x 12 cycles or longer if deriving clinical benefit
Patients with less than PR after 2 cycles or less than CR after 4 cycles were allowed to receive Dexamethasone (Decadron) 20 mg prior to each dose of carfilzomib.
References
- Vij R, Wang M, Kaufman JL, Lonial S, Jakubowiak AJ, Stewart AK, Kukreti V, Jagannath S, McDonagh KT, Alsina M, Bahlis NJ, Reu FJ, Gabrail NY, Belch A, Matous JV, Lee P, Rosen P, Sebag M, Vesole DH, Kunkel LA, Wear SM, Wong AF, Orlowski RZ, Siegel DS. An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma. Blood. 2012 Jun 14;119(24):5661-70. Epub 2012 May 3. link to original article contains verified protocol PubMed
- Jagannath S, Vij R, Stewart AK, Trudel S, Jakubowiak AJ, Reiman T, Somlo G, Bahlis N, Lonial S, Kunkel LA, Wong A, Orlowski RZ, Siegel DS. An open-label single-arm pilot phase II study (PX-171-003-A0) of low-dose, single-agent carfilzomib in patients with relapsed and refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2012 Oct;12(5):310-8. link to original article contains protocol PubMed
- Siegel DS, Martin T, Wang M, Vij R, Jakubowiak AJ, Lonial S, Trudel S, Kukreti V, Bahlis N, Alsina M, Chanan-Khan A, Buadi F, Reu FJ, Somlo G, Zonder J, Song K, Stewart AK, Stadtmauer E, Kunkel L, Wear S, Wong AF, Orlowski RZ, Jagannath S. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood. 2012 Oct 4;120(14):2817-25. Epub 2012 Jul 25. link to original article contains verified protocol PubMed Pivotal trial for accelerated FDA approval
- Subset analysis: Jakubowiak AJ, Siegel DS, Martin T, Wang M, Vij R, Lonial S, Trudel S, Kukreti V, Bahlis N, Alsina M, Chanan-Khan A, Buadi F, Reu FJ, Somlo G, Zonder J, Song K, Stewart AK, Stadtmauer E, Harrison BL, Wong AF, Orlowski RZ, Jagannath S. Treatment outcomes in patients with relapsed and refractory multiple myeloma and high-risk cytogenetics receiving single-agent carfilzomib in the PX-171-003-A1 study. Leukemia. 2013 Dec;27(12):2351-6. Epub 2013 May 14. link to original article PubMed
- Badros AZ, Vij R, Martin T, Zonder JA, Kunkel L, Wang Z, Lee S, Wong AF, Niesvizky R. Carfilzomib in multiple myeloma patients with renal impairment: pharmacokinetics and safety. Leukemia. 2013 Aug;27(8):1707-14. Epub 2013 Jan 31. link to PMC article contains verified protocol PubMed
- Lendvai N, Hilden P, Devlin S, Landau H, Hassoun H, Lesokhin AM, Tsakos I, Redling K, Koehne G, Chung DJ, Schaffer WL, Giralt SA. A phase 2 single-center study of carfilzomib 56 mg/m2 with or without low-dose dexamethasone in relapsed multiple myeloma. Blood. 2014 Aug 7;124(6):899-906. Epub 2014 Jun 24. link to original article contains verified protocol PubMed
Carfilzomib & Panobinostat
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Regimen
Study | Evidence |
Berdeja et al. 2015 | Phase II |
- Carfilzomib (Kyprolis) as follows:
- Cycle 1: 20 mg/m2 IV once on days 1 & 2, then 45 mg/m2 IV over 30 minutes on days 8, 9, 15, 16
- Cycle 2 onwards: 45 mg/m2 IV once on days 1, 2, 8, 9, 15, 16
- Panobinostat (Farydak) 30 mg PO once per day on days 1, 3, 5, 15, 17, 19
28-day cycles until progression or intolerance
References
- Berdeja JG, Hart LL, Mace JR, Arrowsmith ER, Essell JH, Owera RS, Hainsworth JD, Flinn IW. Phase I/II Study of the Combination of Panobinostat and Carfilzomib in Patients with Relapsed/Refractory Multiple Myeloma. Haematologica. 2015 Feb 20. [Epub ahead of print] link to original article contains verified protocol PubMed
Car-Pom-d
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Car-Pom-d: Carfilzomib, Pomalidomide, (low-dose) dexamethasone
Regimen
Study | Evidence |
Shah et al. 2013 | Phase II |
There is some ambiguity about the Shah, et al. 2013 regimen if one only reviews the abstract or presentation. The following is based on reconciling both. Patients in Shah, et al. 2013 needed to be refractory to prior lenalidomide therapy.
Initial therapy
- Carfilzomib (Kyprolis) as follows:
- Cycle 1: 20 mg/m2 IV over 30 minutes once per day on days 1, 2, then 27 mg/m2 IV over 30 minutes once per day on days 8, 9, 15, 16
- Cycles 2 to 6: 27 mg/m2 IV over 30 minutes once per day on days 1, 2, 8, 9, 15, 16
- Pomalidomide (Pomalyst) 4 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) as follows:
- Cycles 1 to 3: 40 mg PO/IV once per week on days 1, 8, 15, 22
- Cycles 4 to 6: 20 mg PO/IV once per week on days 1, 8, 15, 22
- "Investigators were permitted to adjust the dose of dexamethasone at any point based on their discretion."
Supportive medications:
- "Anti-viral therapy"
- Aspirin 81 mg PO once per day
- Low molecular weight heparin was used in patients intolerant of aspirin
28-day cycles x 6 cycles, until disease progression, or unacceptable toxicity
Maintenance cycles
Maintenance cycles were from cycle 7 and on.
- Carfilzomib (Kyprolis) 27 mg/m2 IV over 30 minutes once per day on days 1, 2, 15, 16
- Pomalidomide (Pomalyst) 4 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 20 mg PO/IV once per week on days 1, 8, 15, 22
Supportive medications:
- "Anti-viral therapy"
- Aspirin 81 mg PO once per day
- Low molecular weight heparin was used in patients intolerant of aspirin
28-day cycles, given until disease progression, or unacceptable toxicity
References
- Abstract: Jatin J. Shah, MD, Edward A. Stadtmauer, MD, Rafat Abonour, MD, Adam D. Cohen, MD, William I. Bensinger, MD, Cristina Gasparetto, MD, Jonathan L. Kaufman, MD, Suzanne Lentzsch, MD, Dan T. Vogl, MD, Robert Z. Orlowski, MD, PhD, Erica L. Kim, MPH, Marti McKinley, BSN, MBA, Brian G.M. Durie, MD. A Multi-Center Phase I/II Trial of Carfilzomib and Pomalidomide with Dexamethasone (Car-Pom-d) in Patients with Relapsed/Refractory Multiple Myeloma. 2013 ASH Annual Meeting abstract 690. link to abstract link to presentation contains verified protocol
CPR
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CPR: Cyclophosphamide, Prednisone, Revlimid (lenalidomide)
Regimen
Study | Evidence |
Reece et al. 2014 | Phase II |
Details are for the phase II portion of the published phase I/II trial.
- Cyclophosphamide (Cytoxan) 300 mg/m2 PO on days 1, 8, 15
- Prednisone (Sterapred) 100 mg PO once every other day
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
28-day cycles
References
- Reece DE, Masih-Khan E, Atenafu EG, Jimenez-Zepeda VH, Anglin P, Chen C, Kukreti V, Mikhael JR, Trudel S. Phase I-II trial of oral cyclophosphamide, prednisone and lenalidomide for the treatment of patients with relapsed and refractory multiple myeloma. Br J Haematol. 2015 Jan;168(1):46-54. Epub 2014 Aug 22. link to original article contains protocol PubMed
CRd; KRd
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CRd: Carfilzomib, Revlimid (Lenalidomide), (low-dose) dexamethasone
KRd: Kyprolis (Carfilzomib), Revlimid (Lenalidomide), (low-dose) dexamethasone
Regimen #1
Study | Evidence | Comparator | Efficacy |
Stewart et al. 2014 (ASPIRE) | Phase III | Rd | Superior PFS |
- Carfilzomib (Kyprolis) as follows:
- Cycle 1: 20 mg/m2 IV over 10 minutes once per day on days 1 & 2, then 27 mg/m2 IV over 10 minutes once per day on days 8, 9, 15, 16
- Cycles 2 to 12: 27 mg/m2 IV over 10 minutes once per day on days 1, 2, 8, 9, 15, 16
- Cycles 13 to 18: 27 mg/m2 IV over 10 minutes once per day on days 1, 2, 15, 16
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 40 mg PO once per week on days 1, 8, 15, 22
Supportive medications:
- Valacyclovir (Valtrex) (dose not specified) or equivalent antiviral while taking Lenalidomide (Revlimid)
- Aspirin (dose not specified) or other anticoagulant or antiplatelet medication such as Clopidogrel (Plavix), low-molecular-weight heparin or Warfarin (Coumadin) while taking Lenalidomide (Revlimid)
- Bisphosphonates while taking Dexamethasone (Decadron)
- Lansoprazole (Prevacid) (dose not specified) or other proton pump inhibitor while taking Dexamethasone (Decadron)
- A prophylactic antibiotic (Ciprofloxacin (Cipro), Amoxicillin, Trimethoprim/Sulfamethoxazole (Bactrim DS) are given as examples)
28-day cycles until progression or intolerable side effects (Carfilzomib stopped after 18 cycles)
Regimen #2
Study | Evidence |
Wang et al. 2013 | Phase II |
- Carfilzomib (Kyprolis) as follows:
- Cycle 1: 20 mg/m2 IV once per day on days 1 & 2, then 27 mg/m2 IV once per day on days 8, 9, 15, 16
- Cycles 2 to 12: 27 mg/m2 IV once per day on days 1, 2, 8, 9, 15, 16
- Cycles 13 to 18: 27 mg/m2 IV once per day on days 1, 2, 15, 16
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 40 mg PO once per week on days 1, 8, 15, 22
28-day cycle x up to 18 cycles, longer duration allowed at discretion of investigator
Patients with at least SD after 4 cycles received up to 12 cycles; patients with at least SD after 12 cycles received up to 18 cycles.
References
- Wang M, Martin T, Bensinger W, Alsina M, Siegel DS, Kavalerchik E, Huang M, Orlowski RZ, Niesvizky R. Phase 2 dose-expansion study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma. Blood. 2013 Oct 31;122(18):3122-8. Epub 2013 Sep 6. link to original article contains verified protocol PubMed
- Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Spicka I, Oriol A, Hájek R, Rosiñol L, Siegel DS, Mihaylov GG, Goranova-Marinova V, Rajnics P, Suvorov A, Niesvizky R, Jakubowiak AJ, San-Miguel JF, Ludwig H, Wang M, Maisnar V, Minarik J, Bensinger WI, Mateos MV, Ben-Yehuda D, Kukreti V, Zojwalla N, Tonda ME, Yang X, Xing B, Moreau P, Palumbo A; the ASPIRE Investigators. Carfilzomib, Lenalidomide, and Dexamethasone for Relapsed Multiple Myeloma. N Engl J Med. 2015 Jan 8;372(2):142-52. Epub 2014 Dec 6. link to original article contains verified protocol PubMed
CTD
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CTD: Cyclophosphamide, Thalidomide, Dexamethasone
Regimen
Study | Evidence |
Dimopoulos et al. 2004 | Phase II |
- Cyclophosphamide (Cytoxan) 150 mg/m2 PO every 12 hours (before meals) on days 1 to 5
- Thalidomide (Thalomid) as follows:
- Cycles 1 to 3: 400 mg PO every evening on days 1 to 5 and 14 to 18
- Cycle 4 onwards: 400 mg PO every evening on days 1 to 5
- Dexamethasone (Decadron) as follows:
- Cycles 1 to 3: 20 mg PO every morning after breakfast on days 1 to 5 and 14 to 18
- Cycle 4 onwards: 20 mg PO every morning after breakfast on days 1 to 5
28-day cycles
References
- Dimopoulos MA, Hamilos G, Zomas A, Gika D, Efstathiou E, Grigoraki V, Poziopoulos C, Xilouri I, Zorzou MP, Anagnostopoulos N, Anagnostopoulos A. Pulsed cyclophosphamide, thalidomide and dexamethasone: an oral regimen for previously treated patients with multiple myeloma. Hematol J. 2004;5(2):112-7. PubMed
DCEP
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DCEP: Dexamethasone, Cyclophosphamide, Etoposide, Platinol (Cisplatin)
Regimen #1
Study | Evidence |
Lazzarino et al. 2001 | Phase II |
Note: this protocol is reported as a mobilization regimen prior to high dose autologous transplant; all patients had received prior therapy.
- Dexamethasone (Decadron) 40 mg once per day on days 1 to 4
- Cyclophosphamide (Cytoxan) 400 mg/m2/day (total dose per cycle: 1600 mg/m2) IV continuous infusion over 4 days on days 1 to 4
- Etoposide (Vepesid) 40 mg/m2/day (total dose per cycle: 160 mg/m2) IV continuous infusion over 4 days on days 1 to 4
- Cisplatin (Platinol) 10 mg/m2/day (total dose per cycle: 40 mg/m2) IV continuous infusion over 4 days on days 1 to 4
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting 48 hours after chemotherapy and continuing through stem cell collection
One course
Regimen #2
Study | Evidence |
Dadacaridou et al. 2007 | Phase II, <20 patients reported |
These limited details are based on the abstract's description only. Full article was not available for review.
- Dexamethasone (Decadron) 40 mg IV bolus once per day on days 1 to 4
- Cyclophosphamide (Cytoxan) 400 mg/m2/day (total dose per cycle: 1600 mg/m2) IV continuous infusion over 4 days on days 1 to 4
- Etoposide (Vepesid) 40 mg/m2/day (total dose per cycle: 160 mg/m2) IV continuous infusion over 4 days on days 1 to 4
- Cisplatin (Platinol) 15 mg/m2/day (total dose per cycle: 60 mg/m2) IV continuous infusion over 4 days on days 1 to 4
Supportive medications:
- G-CSF SC once per day, starting on day 5, to continue until neutrophil recovery
28-day cycles
References
- Lazzarino M, Corso A, Barbarano L, Alessandrino EP, Cairoli R, Pinotti G, Ucci G, Uziel L, Rodeghiero F, Fava S, Ferrari D, Fiumanò M, Frigerio G, Isa L, Luraschi A, Montanara S, Morandi S, Perego D, Santagostino A, Savarè M, Vismara A, Morra E. DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) is an effective regimen for peripheral blood stem cell collection in multiple myeloma. Bone Marrow Transplant. 2001 Nov;28(9):835-9. link to original article contains verified protocol PubMed
- Dadacaridou M, Papanicolaou X, Maltesas D, Megalakaki C, Patos P, Panteli K, Repousis P, Mitsouli-Mentzikof C. Dexamethasone, cyclophosphamide, etoposide and cisplatin (DCEP) for relapsed or refractory multiple myeloma patients. J BUON. 2007 Jan-Mar;12(1):41 to 4. PubMed
Dexamethasone (Decadron)
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Regimen #1
Study | Evidence | Comparator | Efficacy |
San Miguel et al. 2013 (MM-003) | Phase III | PD | Inferior PFS |
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
28-day cycles until disease progression or unacceptable toxicity
Regimen #2
Study | Evidence | Comparator | Efficacy |
Weber et al. 2007 (MM-009) | Phase III | RD | Seems to have inferior OS |
Dimopoulos et al. 2007 (MM-010) | Phase III | RD | Seems to have inferior OS |
- Dexamethasone (Decadron) as follows:
- Cycles 1 to 4: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
- Cycle 5 onwards: 40 mg PO once per day on days 1 to 4
28-day cycles until progression or intolerable side effects
Regimen #3, "LoDEX"
Study | Evidence | Comparator | Efficacy |
Richardson et al. 2014 | Randomized phase II, >20 patients | POM+LoDEX (PD) | Seems to have inferior PFS |
- Dexamethasone (Decadron) 40 mg PO once per day on days 1, 8, 15, 22
Supportive medications:
- Aspirin 81 to 100 mg per day unless contraindicated
28-day cycles until disease progression or unacceptable toxicity
References
- Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, San Miguel J, Hellmann A, Facon T, Foà R, Corso A, Masliak Z, Olesnyckyj M, Yu Z, Patin J, Zeldis JB, Knight RD; Multiple Myeloma (010) Study Investigators. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007 Nov 22;357(21):2123-32. link to original article contains verified protocol PubMed
- Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, Siegel D, Borrello I, Rajkumar SV, Chanan-Khan AA, Lonial S, Yu Z, Patin J, Olesnyckyj M, Zeldis JB, Knight RD; Multiple Myeloma (009) Study Investigators. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007 Nov 22;357(21):2133-42. link to original article contains verified protocol PubMed
- Update: Dimopoulos MA, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer EA, Petrucci MT, Yu Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM. Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia. 2009 Nov;23(11):2147-52. Epub 2009 Jul 23. link to original article PubMed
- San Miguel J, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Belch A, Palumbo A, Schey S, Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M, Dimopoulos M. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Oct;14(11):1055-66. Epub 2013 Sep 3. link to original article contains verified protocol PubMed
- Richardson PG, Siegel DS, Vij R, Hofmeister CC, Baz R, Jagannath S, Chen C, Lonial S, Jakubowiak A, Bahlis N, Song K, Belch A, Raje N, Shustik C, Lentzsch S, Lacy M, Mikhael J, Matous J, Vesole D, Chen M, Zaki MH, Jacques C, Yu Z, Anderson K. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood. 2014 Mar 20;123(12):1826-32. Epub 2014 Jan 13. Erratum in: Blood. 2014 May 15;123(20):3208-9. link to original article contains verified protocol PubMed
DTPACE
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DTPACE: Dexamethasone, Thalidomide, Platinum (Cisplatin), Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide
Regimen
Study | Evidence |
Lee et al. 2003 | Prospective |
To be completed
References
- Lee CK, Barlogie B, Munshi N, Zangari M, Fassas A, Jacobson J, van Rhee F, Cottler-Fox M, Muwalla F, Tricot G. DTPACE: an effective, novel combination chemotherapy with thalidomide for previously treated patients with myeloma. J Clin Oncol. 2003 Jul 15;21(14):2732-9. Erratum in: J Clin Oncol. 2008 Apr 20;26(12): 2066. link to original article PubMed
Hyper-CVAD
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Hyper-CVAD: Hyperfractionated Cyclophosphamide, Vincristine, Adriamycin (Doxorubicin), Dexamethasone
Regimen
Study | Evidence |
Dimopoulos et al. 1996 | Phase II |
To be completed
References
- Dimopoulos MA, Weber D, Kantarjian H, Delasalle KB, Alexanian R. HyperCVAD for VAD-resistant multiple myeloma. Am J Hematol. 1996 Jun;52(2):77-81. link to original article PubMed
PCP
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PCP: Pomalidomide, Cyclophosphamide, Prednisone
Regimen
Study | Evidence |
Larocca et al. 2013 | Phase II |
Details are for the phase II portion of the published phase I/II trial.
Induction
- Pomalidomide (Pomalyst) 2.5 mg PO once per day
- Cyclophosphamide (Cytoxan) 50 mg PO once every other day
- Prednisone (Sterapred) 50 mg PO once every other day
Supportive medications:
- Aspirin 100 mg PO once per day or low-molecular-weight heparin "according to patient risk"
28-day cycles x 6 cycles, followed by:
Maintenance
- Pomalidomide (Pomalyst) 1 mg PO once per day
- Prednisone (Sterapred) 25 mg PO once every other day
Supportive medications:
- Aspirin 100 mg PO once per day or low-molecular-weight heparin "according to patient risk"
Continuously until any signs of relapse or progression
References
- Larocca A, Montefusco V, Bringhen S, Rossi D, Crippa C, Mina R, Galli M, Marcatti M, La Verde G, Giuliani N, Magarotto V, Guglielmelli T, Rota-Scalabrini D, Omedé P, Santagostino A, Baldi I, Carella AM, Boccadoro M, Corradini P, Palumbo A. Pomalidomide, cyclophosphamide and prednisone for relapsed/refractory multiple myeloma: a multicenter phase 1/2 open label study. Blood. 2013 Oct 17;122(16):2799-806. Epub 2013 Aug 16. link to original article contains verified protocol PubMed
PD
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PD: Pomalidomide, Dexamethasone
Regimen #1
Study | Evidence | Comparator | Efficacy |
San Miguel et al. 2013 (MM-003) | Phase III | Dexamethasone | Superior PFS |
Leleu et al. 2013 (IFM 2009-02) | Randomized phase II, >20 patients | Pom-Dex (28/28) | Seems not superior |
Richardson et al. 2014 | Randomized phase II, >20 patients | LoDEX (Dexamethasone) | Seems to have superior PFS |
Leleu et al. 2015 (IFM 2010-02) | Phase II |
- Pomalidomide (Pomalyst) 4 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 40 mg (20 mg for patients >75 years old) PO once per day on days 1, 8, 15, 22
Supportive medications:
- San Miguel et al. 2013: Thromboprohpylaxis required. "Choice of thromboprophylaxis and use of myeloid and erythroid growth factors was left to the physician's discretion."
- Leleu et al. 2013: Thromboprophylaxis "at the physician's discretion"
- Leleu et al. 2013: G-CSF allowed beginning with cycle 2 and on
- Richardson et al. 2014: Aspirin 81 to 100 mg once per day unless contraindicated
28-day cycles until disease progression or unacceptable toxicity
Regimen #2
Study | Evidence | Comparator | Efficacy |
Lacy et al. 2011 | Phase II | ||
Leleu et al. 2013 (IFM 2009-02) | Randomized phase II, >20 patients | Pom-Dex (21/28) | Seems not superior |
- Pomalidomide (Pomalyst) 4 mg PO once per day on days 1 to 28
- Dexamethasone (Decadron) 40 mg PO once per day on day 1, 8, 15, 22
Supportive medications:
- Lacy et al. 2011: Aspirin 325 mg PO once per day; low molecular weight heparin or Warfarin (Coumadin) could be substituted at physician discretion
- Leleu et al. 2013: Thromboprophylaxis "at the physician's discretion"
- Leleu et al. 2013: G-CSF allowed beginning with cycle 2 and on
28-day cycles, given until disease progression or unacceptable toxicity
Regimen #3
Study | Evidence | ||
Lacy et al. 2009 | Phase II | ||
Lacy et al. 2010 | Phase II | ||
Lacy et al. 2011 | Phase II |
- Pomalidomide (Pomalyst) 2 mg PO once per day on days 1 to 28
- Dexamethasone (Decadron) 40 mg PO once per day on day 1, 8, 15, 22
Supportive medications:
- Aspirin 325 mg PO once per day; low molecular weight heparin or Warfarin (Coumadin) could be substituted at physician discretion
28-day cycles given until disease progression or unacceptable toxicity
References
- Lacy MQ, Hayman SR, Gertz MA, Dispenzieri A, Buadi F, Kumar S, Greipp PR, Lust JA, Russell SJ, Dingli D, Kyle RA, Fonseca R, Bergsagel PL, Roy V, Mikhael JR, Stewart AK, Laumann K, Allred JB, Mandrekar SJ, Rajkumar SV. Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J Clin Oncol. 2009 Oct 20;27(30):5008-14. Epub 2009 Aug 31. link to original article contains verified protocol PubMed
- Lacy MQ, Hayman SR, Gertz MA, Short KD, Dispenzieri A, Kumar S, Greipp PR, Lust JA, Russell SJ, Dingli D, Zeldenrust S, Fonseca R, Bergsagel PL, Roy V, Mikhael JR, Stewart AK, Laumann K, Allred JB, Mandrekar SJ, Rajkumar SV, Buadi F. Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). Leukemia. 2010 Nov;24(11):1934-9. Epub 2010 Sep 9. link to original article contains verified protocol PubMed
- Lacy MQ, Allred JB, Gertz MA, Hayman SR, Short KD, Buadi F, Dispenzieri A, Kumar S, Greipp PR, Lust JA, Russell SJ, Dingli D, Zeldenrust S, Fonseca R, Bergsagel PL, Roy V, Stewart AK, Laumann K, Mandrekar SJ, Reeder C, Rajkumar SV, Mikhael JR. Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. Blood. 2011 Sep 15;118(11):2970-5. Epub 2011 Jun 20. link to original article contains verified protocol PubMed
- Leleu X, Attal M, Arnulf B, Moreau P, Traulle C, Marit G, Mathiot C, Petillon MO, Macro M, Roussel M, Pegourie B, Kolb B, Stoppa AM, Hennache B, Bréchignac S, Meuleman N, Thielemans B, Garderet L, Royer B, Hulin C, Benboubker L, Decaux O, Escoffre-Barbe M, Michallet M, Caillot D, Fermand JP, Avet-Loiseau H, Facon T. Pomalidomide plus low dose dexamethasone is active and well tolerated in bortezomib and lenalidomide refractory multiple myeloma: IFM 2009-02. 2013 Mar 14;121(11):1968-1975. Epub 2013 Jan 14. link to original article contains verified protocol PubMed
- San Miguel J, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Belch A, Palumbo A, Schey S, Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M, Dimopoulos M. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Oct;14(11):1055-66. Epub 2013 Sep 3. link to original article contains verified protocol PubMed
- Richardson PG, Siegel DS, Vij R, Hofmeister CC, Baz R, Jagannath S, Chen C, Lonial S, Jakubowiak A, Bahlis N, Song K, Belch A, Raje N, Shustik C, Lentzsch S, Lacy M, Mikhael J, Matous J, Vesole D, Chen M, Zaki MH, Jacques C, Yu Z, Anderson K. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood. 2014 Mar 20;123(12):1826-32. Epub 2014 Jan 13. Erratum in: Blood. 2014 May 15;123(20):3208-9. link to original article contains verified protocol PubMed
- Leleu X, Karlin L, Macro M, Hulin C, Garderet L, Roussel M, Arnulf B, Pegourie B, Kolb B, Stoppa AM, Brechiniac S, Marit G, Thielemans B, Onraed B, Mathiot C, Banos A, Lacotte L, Tiab M, Dib M, Fuzibet JG, Petillon MO, Rodon P, Wetterwald M, Royer B, Legros L, Benboubker L, Decaux O, Escoffre-Barbe M, Caillot D, Fermand JP, Moreau P, Attal M, Avet-Loiseau H, Facon T; Intergroupe Francophone du Myélome (IFM). Pomalidomide plus low-dose dexamethasone in multiple myeloma with deletion 17p and/or translocation (4;14): IFM 2010-02 trial results. Blood. 2015 Feb 26;125(9):1411-7. Epub 2015 Jan 9. link to original article contains verified protocol PubMed
RD; Rd
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RD: Revlimid (Lenalidomide), Dexamethasone
Rd: Revlimid (Lenalidomide), (low-dose) dexamethasone
Regimen #1
Study | Evidence | Comparator | Efficacy |
Stewart et al. 2014 (ASPIRE) | Phase III | CRd | Inferior PFS |
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 40 mg PO once per week on days 1, 8, 15, 22
Supportive medications:
- Valacyclovir (Valtrex) (dose not specified) or equivalent antiviral while taking Lenalidomide (Revlimid)
- Aspirin (dose not specified) or other anticoagulant or antiplatelet medication such as Clopidogrel (Plavix), low-molecular-weight heparin or Warfarin (Coumadin) while taking Lenalidomide (Revlimid)
- Bisphosphonates while taking Dexamethasone (Decadron)
- Lansoprazole (Prevacid) (dose not specified) or other proton pump inhibitor while taking Dexamethasone (Decadron)
- A prophylactic antibiotic (Ciprofloxacin (Cipro), Amoxicillin, Trimethoprim/Sulfamethoxazole (Bactrim DS) are given as examples)
28-day cycles until progression or intolerable side effects
Regimen #2
Study | Evidence | Comparator | Efficacy |
Weber et al. 2007 (MM-009) | Phase III | Dexamethasone | Seems to have superior OS |
Dimopoulos et al. 2007 (MM-010) | Phase III | Dexamethasone | Seems to have superior OS |
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) as follows:
- Cycles 1 to 4: 40 mg PO once per day on days 1 to 4, 9 to 12, 17 to 20
- Cycle 5 onwards: 40 mg PO once per day on days 1 to 4
28-day cycles until progression or intolerable side effects
References
- Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, San Miguel J, Hellmann A, Facon T, Foà R, Corso A, Masliak Z, Olesnyckyj M, Yu Z, Patin J, Zeldis JB, Knight RD; Multiple Myeloma (010) Study Investigators. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007 Nov 22;357(21):2123-32. link to original article contains verified protocol PubMed
- Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, Siegel D, Borrello I, Rajkumar SV, Chanan-Khan AA, Lonial S, Yu Z, Patin J, Olesnyckyj M, Zeldis JB, Knight RD; Multiple Myeloma (009) Study Investigators. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007 Nov 22;357(21):2133-42. link to original article contains verified protocol PubMed
- Update: Dimopoulos MA, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer EA, Petrucci MT, Yu Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM. Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia. 2009 Nov;23(11):2147-52. Epub 2009 Jul 23. link to original article PubMed
- Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Spicka I, Oriol A, Hájek R, Rosiñol L, Siegel DS, Mihaylov GG, Goranova-Marinova V, Rajnics P, Suvorov A, Niesvizky R, Jakubowiak AJ, San-Miguel JF, Ludwig H, Wang M, Maisnar V, Minarik J, Bensinger WI, Mateos MV, Ben-Yehuda D, Kukreti V, Zojwalla N, Tonda ME, Yang X, Xing B, Moreau P, Palumbo A; the ASPIRE Investigators. Carfilzomib, Lenalidomide, and Dexamethasone for Relapsed Multiple Myeloma. N Engl J Med. 2015 Jan 8;372(2):142-52. Epub 2014 Dec 6. link to original article contains verified protocol PubMed
RVD
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RVD: Revlimid (Lenalidomide), Velcade (Bortezomib), Dexamethasone
Regimen
Study | Evidence |
Richardson et al. 2014 | Phase II |
- Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 14
- Bortezomib (Velcade) 1.0 mg/m2 IV once per day on days 1, 4, 8, 11
- Dexamethasone (Decadron) as follows:
- Cycles 1 to 4: 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
- Cycles 5 to 8: 10 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
Supportive medications:
21-day cycles x 8 cycles
Patients who had at least stable disease and tolerated therapy could proceed to maintenance RVD at previously tolerated dose.
References
- Richardson PG, Xie W, Jagannath S, Jakubowiak A, Lonial S, Raje NS, Alsina M, Ghobrial IM, Schlossman RL, Munshi NC, Mazumder A, Vesole DH, Kaufman JL, Colson K, McKenney M, Lunde LE, Feather J, Maglio ME, Warren D, Francis D, Hideshima T, Knight R, Esseltine DL, Mitsiades CS, Weller E, Anderson KC. A phase II trial of lenalidomide, bortezomib and dexamethasone in patients with relapsed and relapsed/refractory myeloma. Blood. 2014 Mar 6;123(10):1461-9. Epub 2014 Jan 15. link to original article contains verified protocol PubMed
TD, Thal-Dex
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TD: Thalidomide, Dexamethasone
Thal-Dex: Thalidomide, Dexamethasone
Regimen #1
Study | Evidence | Comparator |
Garderet et al. 2012 (MMVAR/IFM 2005-04) | Phase III | VTD |
Intended for patients who have relapsed after an autologous stem-cell transplant
- Thalidomide (Thalomid) 200 mg PO once per day
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4 of a 21-day cycle
Supportive medications:
- Enoxaparin (Lovenox) 40 mg SC once per day for primary prophylaxis; Warfarin (Coumadin) for secondary prophylaxis
One year of treatment
Regimen #2
Study | Evidence | Comparator | Efficacy |
Hjorth et al. 2012 | Phase III | Bort-Dex | Equivalent PFS |
- Thalidomide (Thalomid) 50 mg PO once per day, increased by 50 mg every 3 weeks to a maximum of 200 mg PO once per day "unless sufficient response was achieved by a lower dose"
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
Supportive medications:
- "Antithrombotic prophylaxis and acyclovir prophylaxis were not mandatory according to the study protocol but used routinely in an increasing proportion of participating centers during the study period."
21-day cycles, to be continued until progression or best response, which would then be followed by 1 to 2 additional cycles
References
- Hjorth M, Hjertner Ø, Knudsen LM, Gulbrandsen N, Holmberg E, Pedersen PT, Andersen NF, Andréasson B, Billström R, Carlson K, Carlsson MS, Flogegård M, Forsberg K, Gimsing P, Karlsson T, Linder O, Nahi H, Othzén A, Swedin A; Nordic Myeloma Study Group (NMSG). Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan refractory myeloma: a randomized study. Eur J Haematol. 2012 Jun;88(6):485-96. Epub 2012 Mar 30. link to original article contains verified protocol PubMed
- Garderet L, Iacobelli S, Moreau P, Dib M, Lafon I, Niederwieser D, Masszi T, Fontan J, Michallet M, Gratwohl A, Milone G, Doyen C, Pegourie B, Hajek R, Casassus P, Kolb B, Chaleteix C, Hertenstein B, Onida F, Ludwig H, Ketterer N, Koenecke C, van Os M, Mohty M, Cakana A, Gorin NC, de Witte T, Harousseau JL, Morris C, Gahrton G. Superiority of the triple combination of bortezomib-thalidomide-dexamethasone over the dual combination of thalidomide-dexamethasone in patients with multiple myeloma progressing or relapsing after autologous transplantation: the MMVAR/IFM 2005-04 Randomized Phase III Trial from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2012 Jul 10;30(20):2475-82. Epub 2012 May 14. Erratum in: J Clin Oncol. 2012 Sep 20;30(27):3429. link to original article contains verified protocol PubMed
Thalidomide (Thalomid)
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Regimen
Study | Evidence |
Singhal et al. 1999 | Non-randomized |
- Thalidomide (Thalomid) 200 mg PO once per day, increased by 200 mg every two weeks for six weeks, to final dose of 800 mg per day
Continued until progression
References
- Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, Zeddis J, Barlogie B. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999 Nov 18;341(21):1565-71. Erratum in: N Engl J Med 2000 Feb 3;342(5):364. link to original article contains protocol PubMed
Vemurafenib (Zelboraf)
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Regimen
Study | Evidence |
Andrulis et al. 2013 | Case report |
Note that Andrulis et al. 2013 is a single patient case report with a good response. Sharman et al. reports two patients with good response. In the Hyman et al. 2015 trial, there were 5 patients with multiple myeloma; "No patients with multiple myeloma have had a response to date."
- Vemurafenib (Zelboraf) 480 mg PO BID for one week, then increased to 720 mg PO BID
References
- Andrulis M, Lehners N, Capper D, Penzel R, Heining C, Huellein J, Zenz T, von Deimling A, Schirmacher P, Ho AD, Goldschmidt H, Neben K, Raab MS. Targeting the BRAF V600E mutation in multiple myeloma. Cancer Discov. 2013 Aug;3(8):862-9. Epub 2013 Apr 23. link to original article contains protocol PubMed
- Sharman JP, Chmielecki J, Morosini D, Palmer GA, Ross JS, Stephens PJ, Stafl J, Miller VA, Ali SM. Vemurafenib response in 2 patients with posttransplant refractory BRAF V600E-mutated multiple myeloma. Clin Lymphoma Myeloma Leuk. 2014 Oct;14(5):e161-3. Epub 2014 Jun 11. link to original article PubMed
- Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J, Baselga J. Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med. 2015 Aug 20;373(8):726-36. link to original article PubMed
VMPT
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VMPT: Velcade (Bortezomib), Melphalan, Prednisone, Thalidomide
Regimen
Study | Evidence |
Palumbo et al. 2007 | Phase II |
- Bortezomib (Velcade) 1.0 to 1.3 mg/m2 IV bolus once per day on days 1, 4, 15, 22
- Melphalan (Alkeran) 6 mg/m2 PO once per day on days 1 to 5
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
- Thalidomide (Thalomid) 50 mg PO once per day on days 1 to 35
35-day cycles x 6 cycles
References
- Palumbo A, Ambrosini MT, Benevolo G, Pregno P, Pescosta N, Callea V, Cangialosi C, Caravita T, Morabito F, Musto P, Bringhen S, Falco P, Avonto I, Cavallo F, Boccadoro M; Italian Multiple Myeloma Network; Gruppo Italiano Malattie Ematologicche dell'Adulto. Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma. Blood. 2007 Apr 1;109(7):2767-72. link to original article contains protocol PubMed
VTD
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VTD: Velcade (Bortezomib), Thalidomide, Dexamethasone
Regimen
Study | Evidence | Comparator |
Garderet et al. 2012 (MMVAR/IFM 2005-04) | Phase III | TD |
Intended for patients who have relapsed after an autologous stem-cell transplant
- Bortezomib (Velcade) as follows:
- Cycles 1 to 8: 1.3 mg/m2 IV bolus once per day on days 1, 4, 8, 11 of a 21-day cycle
- Cycles 9 to 12: 1.3 mg/m2 IV bolus once per week on days 1, 8, 15, 22 of a 42-day cycle
- Thalidomide (Thalomid) 200 mg PO once per day
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4 of a 21-day cycle
Supportive medications:
- Enoxaparin (Lovenox) 40 mg SC once per day for primary prophylaxis; Warfarin (Coumadin) for secondary prophylaxis
- Herpes zoster prophylaxis highly recommended
One year of treatment
References
- Garderet L, Iacobelli S, Moreau P, Dib M, Lafon I, Niederwieser D, Masszi T, Fontan J, Michallet M, Gratwohl A, Milone G, Doyen C, Pegourie B, Hajek R, Casassus P, Kolb B, Chaleteix C, Hertenstein B, Onida F, Ludwig H, Ketterer N, Koenecke C, van Os M, Mohty M, Cakana A, Gorin NC, de Witte T, Harousseau JL, Morris C, Gahrton G. Superiority of the triple combination of bortezomib-thalidomide-dexamethasone over the dual combination of thalidomide-dexamethasone in patients with multiple myeloma progressing or relapsing after autologous transplantation: the MMVAR/IFM 2005-04 Randomized Phase III Trial from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2012 Jul 10;30(20):2475-82. Epub 2012 May 14. Erratum in: J Clin Oncol. 2012 Sep 20;30(27):3429. link to original article contains verified protocol PubMed
Maintenance after salvage therapy
RVD
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RVD: Revlimid (Lenalidomide), Velcade (Bortezomib), Dexamethasone
Regimen
Study | Evidence |
Richardson et al. 2014 | Phase II |
Treatment preceded by salvage RVD.
- Lenalidomide (Revlimid) (at previously tolerated dose) PO once per day on days 1 to 14
- Bortezomib (Velcade) (at previously tolerated dose) IV once per day on days 1 & 8
- Dexamethasone (Decadron) 10 mg PO once per day on days 1, 2, 8, 9
Supportive medications:
21-day cycles until progression or intolerance
References
- Richardson PG, Xie W, Jagannath S, Jakubowiak A, Lonial S, Raje NS, Alsina M, Ghobrial IM, Schlossman RL, Munshi NC, Mazumder A, Vesole DH, Kaufman JL, Colson K, McKenney M, Lunde LE, Feather J, Maglio ME, Warren D, Francis D, Hideshima T, Knight R, Esseltine DL, Mitsiades CS, Weller E, Anderson KC. A phase II trial of lenalidomide, bortezomib and dexamethasone in patients with relapsed and relapsed/refractory myeloma. Blood. 2014 Mar 6;123(10):1461-9. Epub 2014 Jan 15. link to original article contains verified protocol PubMed
Investigational agents
These are drugs under study with at least some promising results for this disease.
- Afuresertib (GSK2110183)
- Daratumumab (HuMax-CD38)
- Dinaciclib (SCH 727965)
- Elotuzumab (HuLuc63)
- Ixazomib (MLN9708)
- Perifosine (KRX-0401)
- Ricolinostat (ACY-1215, Rocilinostat)
Response criteria
Make note of these errors which remain in the online version as of 7/7/2013.
- International uniform response criteria (e.g. CR, sCR, VGPR, PR, SD) for multiple myeloma. (Leukemia 2006).[1]
- Disease progression criteria (Leukemia 2006).[1]
- European Blood and Marrow Transplant (EBMT) criteria. (Br J Hematol 1998).[2]
Staging
External links
References
- ↑ 1.0 1.1 Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K, Gertz M, Dimopoulos M, Westin J, Sonneveld P, Ludwig H, Gahrton G, Beksac M, Crowley J, Belch A, Boccadaro M, Cavo M, Turesson I, Joshua D, Vesole D, Kyle R, Alexanian R, Tricot G, Attal M, Merlini G, Powles R, Richardson P, Shimizu K, Tosi P, Morgan G, Rajkumar SV; International Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia. 2006 Sep;20(9):1467-73. Epub 2006 Jul 20. link to original article PubMed
- ↑ Bladé J, Samson D, Reece D, Apperley J, Björkstrand B, Gahrton G, Gertz M, Giralt S, Jagannath S, Vesole D. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol. 1998 Sep;102(5):1115-23. link to original article PubMed
- ↑ Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, Boccadoro M, Child JA, Avet-Loiseau H, Kyle RA, Lahuerta JJ, Ludwig H, Morgan G, Powles R, Shimizu K, Shustik C, Sonneveld P, Tosi P, Turesson I, Westin J. International staging system for multiple myeloma. J Clin Oncol. 2005 May 20;23(15):3412-20. Epub 2005 Apr 4. link to original article PubMed
- ↑ Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009 Jan;23(1):3-9. Epub 2008 Oct 30. link to original article PubMed
- ↑ Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975 Sep;36(3):842-54. PubMed