Multiple myeloma
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First-line regimens (including transplant ineligible)
BiRD
BiRD: Biaxin, Revlimid, Dexamethasone
Levels of Evidence: 2007 Phase II
2010
Phase II
Retrospective improved PFS
Retrospective increased toxicity
Regimen
- Clarithromycin (Biaxin) 500 mg PO BID on days 2-28 of cycle 1; 500 mg PO BID on days 1-28 of cycle 2 and thereafter
- Lenalidomide (Revlimid) 25 mg PO once daily on days 3-21 of cycle 1; 25 mg PO once daily on days 1-21 of cycle 2 and thereafter
- Dexamethasone (Decadron) 40 mg PO once daily on days 1, 2, 3, 8, 15, 22 of cycle 1; 40 mg PO once daily on days 1, 8, 15, 22 of cycle 2 and thereafter
28-week cycles
Supportive medications:
- Aspirin 81 mg PO once daily
- Omeprazole (Prilosec) 20 mg PO once daily
- Trimethoprim/Sulfamethoxazole (Bactrim DS) PO BID, 3 times a week
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
- 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
CTD, CTDa
CTD: Cyclophosphamide, Thalidomide, Dexamethasone
CTDa: Cyclophosphamide, Thalidomide, Dexamethasone, attenuated
Regimen #1, Morgan, et al. 2011 - CTDa
CTDa is intended for elderly or non-transplant-eligible patients
- Cyclophosphamide (Cytoxan) 500 mg PO once per week
- Thalidomide (Thalomid) 50 mg PO once daily on days 1-28; dose is increased every 4 weeks in 50 mg increments, up to a maximum dose of 200 mg PO once daily
- Dexamethasone (Decadron) 20 mg PO once daily on days 1-4, 15-18
28-day cycles x 6-9 cycles
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 daily
- Zoledronic acid (Zometa) 4 mg IV once every 21-28 days
Regimen #2, Morgan, et al. 2012 - CTD
- Cyclophosphamide (Cytoxan) 500 mg PO once per week
- Thalidomide (Thalomid) 100 mg PO once daily on days 1-21, increasing to 200 mg PO once daily "if tolerated"
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 12-15
21-day cycles x up to 6 cycles
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 daily
- Zoledronic acid (Zometa) 4 mg IV once every 21-28 days
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. doi: 10.1182/blood-2011-02-338665. Epub 2011 Jun 7. link to original article contains verified protocol PubMed
- 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. doi: 10.3324/haematol.2011.043372. Epub 2011 Nov 4. link to original article contains verified protocol PubMed
CVAD
CVAD: Cyclophosphamide, Vincristine, Adriamycin, Dexamethasone
Regimen
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 daily on days 1-4
- Doxorubicin (Adriamycin) 9 mg/m2/day (total dose per cycle: 36 mg/m2) IV continuous infusion over 4 days on days 1-4
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 12-15
21-day cycles x up to 6 cycles
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 daily
- Zoledronic acid (Zometa) 4 mg IV once every 21-28 days
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. doi: 10.3324/haematol.2011.043372. Epub 2011 Nov 4. link to original article contains verified protocol--see comment above PubMed
CyBorD (CVD)
CyBorD: Cyclophosphamide, Bortezomib, Dexamethasone
CVD: Cyclophosphamide, Velcade, Dexamethasone
Regimen #1, Reeder, et al. 2009
- Cyclophosphamide (Cytoxan) 300 mg/m2 PO once daily on days 1, 8, 15, 22
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 4, 8, 11
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 9-12, 17-20
28-day cycles x 4-12 cycles
Supportive medications:
- Proton pump inhibitor (PPI)
- Acyclovir (Zovirax)
- Quinolone antibiotic
- Antifungal mouthwash recommended
Regimen #2, Kumar, et al. 2012 - EVOLUTION (VDC-mod)
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once daily on days 1, 8, 15
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 4, 8, 11
- Dexamethasone (Decadron) 40 mg PO once daily on days 1, 8, 15
21-day cycles x 8 cycles, then
Maintenance therapy:
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 8, 15, 22
42-day cycles x 4 cycles
Supportive medications:
- Aspirin 325 mg PO once daily
- 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"
Regimen #3, Kumar, et al. 2012 - EVOLUTION (VDC)
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once daily on days 1 & 8
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 4, 8, 11
- Dexamethasone (Decadron) 40 mg PO once daily on days 1, 8, 15
21-day cycles x 8 cycles, then
Maintenance therapy:
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 8, 15, 22
42-day cycles x 4 cycles
Supportive medications:
- Aspirin 325 mg PO once daily
- 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
- 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
- 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
DEX (Dexamethasone)
DEXamethasone
Regimen
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 9-12, 17-20 for cycles 1-2; 40 mg PO once daily on days 1-4 of cycles 3-12
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
DEXamethasone, IFN: Interferon alfa-2b
Regimen
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 9-12, 17-20 for cycles 1-2; 40 mg PO once daily on days 1-4 of cycles 3-12
- 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 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
DVD, DVd
DVD: Doxil, Vincristine, Dexamethasone
Regimen #1, Hussein, et al. 2002
- 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 daily on days 1-4
4-week cycles x 6-8 cycles
Supportive medications:
- Vitamin B6 200 mg PO once daily to help reduce risk of palmar-plantar erythrodysesthesia (PPE)
Regimen #2, Rifkin, et al. 2006
- 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 daily on days 1-4
4-week cycles, given until maximal response, progression of disease, or unacceptable toxicity
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
- 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
MP, M-DEX
MP: Melphalan, Prednisone/rednisolone M-DEX: Melphalan, DEXamethasone
Regimen #1, Facon, et al. 2006
- Melphalan (Alkeran) 0.25 mg/kg PO once daily on days 1-4
- Prednisone (Sterapred) 2 mg/kg PO once daily on days 1-4
6-week cycles x 12 cycles
Regimen #2, San Miguel, et al. 2008
- Melphalan (Alkeran) 9 mg/m2 PO once daily on days 1-4
- Prednisone (Sterapred) 60 mg/m2 PO once daily on days 1-4
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 1-7
- Prednisone (Sterapred) 20 mg PO TID on days 1-7
6-week cycles
Regimen #4, Facon, et al. 2006
- Melphalan (Alkeran) 0.25 mg/kg PO once daily on days 1-4
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 9-12, 17-20 for cycles 1-2; 40 mg PO once daily on days 1-4 of cycles 3-12
6-week cycles x 12 cycles
Regimen #5, Hulin, et al. 2009
- Melphalan (Alkeran) 0.2 mg/kg PO once daily on days 1-4
- Prednisone (Sterapred) 2 mg/kg PO once daily on days 1-4
6-week cycles x 12 cycles
Regimen #6, Palumbo, et al. 2012
- Melphalan (Alkeran) 0.18 mg/kg PO once daily on days 1-4
- Prednisone (Sterapred) 2 mg/kg PO once daily on days 1-4
28-day cycles x 9 cycles
Supportive medications:
- Aspirin 75-100 mg PO once daily as thromboprophylaxis
Regimen #7, Wijermans, et al. 2010 - HOVON 49
- Melphalan (Alkeran) 0.25 mg/kg PO once daily on days 1-5
- Prednisone (Sterapred) 1 mg/kg PO once daily on days 1-5
28-day cycles x 8 cycles
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."
Regimen #8, Morgan, et al. 2011 - MRC Myeloma IX study
- Melphalan (Alkeran) 7 mg/m2 PO once daily on days 1-4
- Prednisolone (Millipred) 40 mg PO once daily on days 1-4
28-day cycles x 6-9 cycles
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 daily
- Zoledronic acid (Zometa) 4 mg IV once every 21-28 days
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
- 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
- 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
- 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. doi: 10.1182/blood-2011-02-338665. Epub 2011 Jun 7. link to original article contains verified protocol PubMed
- Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, Gisslinger H, Wiktor-Jędrzejczak 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
- 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. doi: 10.1200/JCO.2009.26.1610. Epub 2010 Jun 1. link to original article contains verified protocol PubMed
MPR, MPR-R, MPL
MPL: Melphalan, Prednisone, Lenalidomide
MPR: Melphalan, Prednisone, Revlimid
MPR-R: Melphalan, Prednisone, Revlimid, Revlimid maintenance
Regimen #1, Palumbo, et al. 2007 & Palumbo, et al. 2012 - MPR-R
- Melphalan (Alkeran) 0.18 mg/kg PO once daily on days 1-4
- Prednisone (Sterapred) 2 mg/kg PO once daily on days 1-4
- Lenalidomide (Revlimid) 10 mg PO once daily on days 1-21
28-day cycles x 9 cycles, THEN
- Lenalidomide (Revlimid) 10 mg PO once daily on days 1-21
28-day cycles, to continue until relapsed or refractory disease
Supportive medications (varies depending on reference):
- Palumbo et al. 2012: Aspirin 75-100 mg PO once daily as thromboprophylaxis
- Palumbo et al. 2007: Ciprofloxacin (Cipro) 500 mg PO BID and Aspirin 100 mg PO once daily
Regimen #2, Palumbo, et al. 2012 - MPR
- Melphalan (Alkeran) 0.18 mg/kg PO once daily on days 1-4
- Prednisone (Sterapred) 2 mg/kg PO once daily on days 1-4
- Lenalidomide (Revlimid) 10 mg PO once daily on days 1-21
28-day cycles x 9 cycles
Supportive medications:
- Aspirin 75-100 mg PO once daily as thromboprophylaxis
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-Jędrzejczak 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
MPT
MPT: Melphalan, Prednisone, Thalidomide
Regimen #1, Facon, et al. 2007
- Melphalan (Alkeran) 0.25 mg/kg PO once daily on days 1-4
- Prednisone (Sterapred) 2 mg/kg PO once daily on days 1-4
- Thalidomide (Thalomid) 200 mg PO once daily, increased as tolerated after 2-4 weeks on therapy to maximal dose of 400 mg once daily, given on days 1-42
42-day cycles x 12 cycles
Regimen #2, Palumbo, et al. 2006 & Palumbo, et al. 2008
- Melphalan (Alkeran) 4 mg/m2 PO once daily on days 1-7
- Prednisone (Sterapred) 40 mg/m2 PO once daily on days 1-7
- Thalidomide (Thalomid) 100 mg PO once daily on days 1-28
Supportive medications:
- Enoxaparin (Lovenox) 40 mg SC once daily on days 1-28 of cycles 1-4
28-day cycles x 6 cycles, then
- Thalidomide (Thalomid) 100 mg PO daily until evidence of relapse or refractory disease
Regimen #3, Hulin, et al. 2009
- Melphalan (Alkeran) 0.2 mg/kg PO once daily on days 1-4
- Prednisone (Sterapred) 2 mg/kg PO once daily on days 1-4
- Thalidomide (Thalomid) 100 mg PO once daily
42-day cycles x 12 cycles
Regimen #4, Wijermans, et al. 2010 - HOVON 49
Induction therapy
- Melphalan (Alkeran) 0.25 mg/kg PO once daily on days 1-5
- Prednisone (Sterapred) 1 mg/kg PO once daily on days 1-5
- Thalidomide (Thalomid) 200 mg PO once daily
28-day cycles x 8 cycles, then
- Thalidomide (Thalomid) 200 mg PO once daily
28-day course, then
Maintenance therapy
- Thalidomide (Thalomid) 50 mg PO once daily until progression
Supportive medications (for induction & maintenance periods):
- Bisphosphonate use recommended with Pamidronate (Aredia) or Clodronate (Bonefos); "a maximum treatment period of 2 years was recommended in patients without active disease."
- Recommended thromboprophylaxis:
- During induction therapy, low molecular weight heparin use recommended with nadroparin 2,850 units anti-Xa (for patients >90 kg, dose of 5,700 units anti-Xa)
- During maintenance therapy, "low-dose aspirin was advised"
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
- 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
- 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
- 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. doi: 10.1200/JCO.2009.26.1610. Epub 2010 Jun 1. link to original article contains verified protocol PubMed
RD
RD: Revlimid, Dexamethasone
Regimen #1, Rajkumar, et al. 2010 & Gay, et al. 2010 - low-dose dexamethasone
- Lenalidomide (Revlimid) 25 mg PO once daily on days 1-21
- Dexamethasone (Decadron) 40 mg PO once daily on days 1, 8, 15, 22
28-day cycles, either given x 4 cycles prior to transplant, or given until progression of disease or unacceptable toxicity
Supportive medications (as described in Rajkumar, et al. 2010):
- One of the following bisphosphonates:
- Pamidronate (Aredia) 90 mg IV over 2-4 hours once every 4 weeks
- Zoledronic acid (Zometa) 4 mg IV over 15 minutes once every 4 weeks
- Thromboprophylaxis required
Regimen #2, Rajkumar, et al. 2010
- Lenalidomide (Revlimid) 25 mg PO once daily on days 1-21
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 9-12, 17-20
28-day cycles
Supportive medications:
- One of the following bisphosphonates:
- Pamidronate (Aredia) 90 mg IV over 2-4 hours once every 28 days
- Zoledronic acid (Zometa) 4 mg IV over 15 minutes once every 28 days
- "Thromboprophylaxis" aspirin (80 mg or 325 mg per physician discretion) once daily as thrombosis prophylaxis.
Regimen #3, Rajkumar, et al. 2005
- Lenalidomide (Revlimid) 25 mg PO once daily on days 1-21
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 9-12, 17-20 of cycles 1-4; 40 mg PO once daily on days 1-4 of cycle 5 and thereafter
28-day cycles, given until progression of disease or unacceptable toxicity
Supportive medications:
- Aspirin 80 mg or 325 mg (depending on physician choice) PO once daily for thromboprophylaxis
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
- 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)
RVD: Revlimid, Velcade, Dexamethasone
VDR: Velcade, Dexamethasone, Revlimid
Regimen #1, Richardson, et al. 2010
- Lenalidomide (Revlimid) 25 mg PO once daily on days 1-14
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 4, 8, 11
- Dexamethasone (Decadron) 20 mg PO once daily on days 1, 2, 4, 5, 8, 9, 11, 12
21-day cycles x 4-8 cycles
Supportive medications:
- Aspirin 81 mg or 325 mg PO once daily
- Antiviral therapy, such as Acyclovir (Zovirax) 400 mg PO once daily
- Bisphosphonate
Patients who responded and tolerated therapy could proceed to maintenance therapy at previously tolerated dose with a different schedule:
- Lenalidomide (Revlimid) 25 mg (or previously tolerated dose) PO once daily on days 1-14
- Bortezomib (Velcade) 1.3 mg/m2 (or previously tolerated dose) IV once daily on days 1 & 8
- Dexamethasone (Decadron) 20 mg (or previously tolerated dose) PO once daily on days 1, 2, 8, 9
21-day cycles
Regimen #2, Kumar, et al. 2012 - EVOLUTION
- Lenalidomide (Revlimid) 25 mg PO once daily on days 1-14
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 4, 8, 11
- Dexamethasone (Decadron) 40 mg PO once daily on days 1, 8, 15
21-day cycles x 8 cycles, then
Maintenance therapy:
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 8, 15, 22
42-day cycles x 4 cycles
Supportive medications:
- Aspirin 325 mg PO once daily
- 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
- 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
- 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)
RVDC: Revlimid, Velcade, Dexamethasone, Cyclophosphamide
VDCR: Velcade, Dexamethasone, Cyclophosphamide, Revlimid
Regimen - EVOLUTION
- Lenalidomide (Revlimid) 25 mg PO once daily on days 1-14
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 4, 8, 11
- Dexamethasone (Decadron) 40 mg PO once daily on days 1, 8, 15
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once daily on days 1 & 8
21-day cycles x 8 cycles, then
Maintenance therapy:
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 8, 15, 22
42-day cycles x 4 cycles
Supportive medications:
- Aspirin 325 mg PO once daily
- 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
TD
TD: Thalidomide, Dexamethasone
2012: Phase III Decreased PFS Decreased toxicity
Regimen #1, Rajkumar, et al. 2008
- Thalidomide (Thalomid) 50 mg PO once daily on days 1-14 of cycle 1; 100 mg PO once daily on days 15-28 of cycle 1; 200 mg PO once daily on days 1-28 of cycle 2 and thereafter
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 9-12, 17-20 of cycles 1-4; 40 mg PO once daily on days 1-4 of cycle 5 and thereafter
28-day cycles
Regimen #2, Rajkumar, et al. 2002 & Rajkumar, et al. 2006
- Thalidomide (Thalomid) 200 mg PO once daily on days 1-28
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 9-12, 17-20 on odd-numbered cycles; 40 mg PO once daily on days 1-4 of even-numbered cycles
28-day cycles
Regimen #3, Cavo, et al. 2010 & Cavo, et al. 2012 - GIMEMA
- Thalidomide (Thalomid) 100 mg PO once daily on days 1-14 of cycle 1; 200 mg PO once daily on days 15-21 of cycle 1; 200 mg PO once daily on days 1-21 of cycles 2 & 3
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 9-12
21-day cycles x 3 cycles, then
- Melphalan (Alkeran) 200 mg/m2 once on day -2
- Autologous stem cell rescue
Wait until count recovery, then
- Thalidomide (Thalomid) 100 mg PO once daily
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4
28-day cycles for 3-6 months, then
- Melphalan (Alkeran) 200 mg/m2 once on day -2
- Autologous stem cell rescue
Wait until 3 months after second transplant, then
- Thalidomide (Thalomid) 100 mg PO once daily
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 20-23
35-day cycles x 2 cycles, then
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4
28-day cycles until progression, relapse, or undue toxicity
Supportive medications:
- Acyclovir (Zovirax) prophylaxis recommended
Regimen #4, Rosiñol, et al. 2012
- Thalidomide (Thalomid) 50 mg PO once daily on days 1-14 of cycle 1; 100 mg PO once daily on days 15-28 of cycle 1; 200 mg PO once daily on days 1-28 of cycle 2 and thereafter
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 9-12
28-day cycles x 6 cycles
Supportive medications:
- Low-molecular weight heparin or aspirin recommended
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
- 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, 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
VAD: Velcade, Adriamycin, Dexamethasone
PAD: PS-341, Adriamycin, Dexamethasone
Regimen #1, Broyl, et al. 2010 & Sonneveld, et al. 2012 - HOVON-65/GMMG-HD4
Induction therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 4, 8, 11
- Doxorubicin (Adriamycin) 9 mg/m2 IV once daily on days 1-4
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 9-12, 17-20
28-day cycles x 3 cycles; stem cells collected 4-6 weeks after induction therapy
Supportive medications (described in the appendix of Sonneveld, et al. 2012):
- One of the following bisphosphonates recommended:
- Pamidronate (Aredia) 90 mg IV once every 4-6 weeks x at least 2 years
- Zoledronic acid (Zometa) 4 mg IV once every 4-6 weeks x at least 2 years
- Ibandronate (Boniva) 6 mg IV once every 4-6 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)
Regimen #2, Oakervee, et al. 2005
- Bortezomib (Velcade) 1.3 mg/m2 IV bolus once daily on days 1, 4, 8, 11
- Doxorubicin (Adriamycin) 4.5-9 mg/m2 IV once daily on days 1-4
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 8-11, 15-18 of cycle 1; 40 mg PO once daily on days 1-4 of cycles 2-4
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
- Broyl A, Corthals SL, Jongen JL, van der Holt B, Kuiper R, de Knegt Y, van Duin M, el Jarari L, Bertsch U, Lokhorst HM, Durie BG, Goldschmidt H, Sonneveld P. Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma: a prospective analysis of data from the HOVON-65/GMMG-HD4 trial. Lancet Oncol. 2010 Nov;11(11):1057-65. Epub 2010 Sep 21. 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. doi: 10.1200/JCO.2011.39.6820. Epub 2012 Jul 16. link to original article contains verified protocol PubMed
VAD (Vincristine)
VAD: Vincristine, Adriamycin, Dexamethasone
Regimen #1, Barlogie, et al. 1984
- Vincristine (Oncovin) 0.4 mg/day (total dose per cycle: 1.6 mg) IV continuous infusion over 96 hours on days 1-4
- Doxorubicin (Adriamycin) 9 mg/m2/day (total dose per cycle: 36 mg/m2) IV continuous infusion over 96 hours on days 1-4
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 9-12, 17-20
Cycle duration not specified; repeat for four cycles past best response
Supportive medications:
- Cimetidine (dose not specified)
- Trimethoprim/Sulfamethoxazole (dose not specified)
Regimen #2, Segeren, et al. 1999
- Vincristine (Oncovin) 0.4 mg IV over 30 minutes once daily on days 1-4
- Doxorubicin (Adriamycin) 9 mg/m2 IV over 30 minutes once daily on days 1-4
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 9-12, 17-20 of odd-numbered cycles only
4-week cycles
Supportive medications:
- Fluconazole (Diflucan) 200 mg PO daily
- Trimethoprim/Sulfamethoxazole 960 mg (paper did not specify which component was 960 mg) PO BID for "prophylaxis"
Regimen #3, Berenson, et al. 2002 - prednisone maintenance
- Vincristine (Oncovin) 0.4 mg/day (total dose per cycle: 1.6 mg) IV continuous infusion over 4 days on days 1-4
- Doxorubicin (Adriamycin) 9 mg/m2/day (total dose per cycle: 36 mg/m2) IV continuous infusion over 4 days on days 1-4
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4
- Prednisone (Sterapred) 50 mg PO once daily 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 9-12 months of therapy were then started on maintenance therapy:
- Prednisone (Sterapred) 50 mg PO once every other day
Regimen #4, Dimopoulos, et al. 2003
- Vincristine (Oncovin) 0.4 mg IV over 30 minutes on days 1-4
- Doxorubicin (Adriamycin) 9 mg/m2 IV over 30 minutes on days 1-4
- Dexamethasone (Decadron) 40 mg PO on days 1-4; in cycles 1 & 3, Dexamethasone (Decadron) 40 mg PO is also given on days 9-12, 17-20
4-week cycles x 4 cycles
Supportive medications (which were in the cited Segeren, et al. 1999 reference):
- Fluconazole (Diflucan) 200 mg PO once daily
- Trimethoprim/Sulfamethoxazole 960 mg (paper did not specify which component was 960 mg) PO BID for "prophylaxis"
Regimen #5, Rifkin, et al. 2006
- Vincristine (Oncovin) 0.4 mg/day (total dose per cycle: 1.6 mg) IV continuous infusion over 96 hours on days 1-4
- Doxorubicin (Adriamycin) 9 mg/m2/day (total dose per cycle: 36 mg/m2) IV continuous infusion over 96 hours on days 1-4
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4
28-day cycles
Regimen #6, Harousseau, et al. 2010
- Vincristine (Oncovin) 0.4 mg/day (total dose per cycle: 1.6 mg) IV continuous infusion over 4 days on days 1-4
- Doxorubicin (Adriamycin) 9 mg/m2/day (total dose per cycle: 36 mg/m2) IV continuous infusion over 4 days on days 1-4
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 9-12, 17-20 of cycles 1 & 2; 40 mg PO once daily on days 1-4 of cycles 3 and thereafter
28-day cycles
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."
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 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
- 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
VD (Velcade)
VD: Velcade, Dexamethasone
Regimen, Harousseau, et al. 2010 - IFM 2005-01
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 4, 8, 11
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 9-12 of cycles 1 & 2; 40 mg PO once daily on days 1-4 of cycles 3 & 4
21-day cycles x 4 cycles
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."
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
- 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
VDD; PAD
VDD: Velcade, Doxil, Dexamethasone
PAD: PS-341, liposomal Adriamycin, Dexamethasone
Regimen #1, Jakubowiak, et al. 2009 & Dytfeld, et al. 2011
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 4, 8, 11
- Doxorubicin liposomal (Doxil) 30 mg/m2 IV once on day 4
- Dexamethasone (Decadron) 40 mg PO once daily on days 1, 2, 4, 5, 8, 9, 11, 12 of cycle 1; 20 mg PO once daily on days 1, 2, 4, 5, 8, 9, 11, 12 of cycles 2-6
21-day cycles x 6 cycles
Supportive medications:
- Low-molecular weight heparin 40 mg SC once daily or Aspirin 81 mg PO once daily for DVT prophylaxis
- Acyclovir (Zovirax) 400 mg PO BID for Herpes zoster prophylaxis
Regimen #2, Palumbo, et al. 2010
Induction therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 4, 8, 11
- Doxorubicin liposomal (Doxil) 30 mg/m2 IV once on day 4
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 8-11, 15-18 of cycle 1; 40 mg PO once daily on days 1-4 of cycles 2-4
21-day cycles x 4 cycles, THEN
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 daily on days 1-21
- Prednisone (Sterapred) 50 mg PO once every other day
28-day cycles x 4 cycles, THEN
Maintenance
- Lenalidomide (Revlimid) 10 mg PO once daily on days 1-21
28-day cycles, given until relapsed disease
Supportive medications:
- Aspirin 100mg PO once daily during lenalidomide treatment
- Acyclovir (Zovirax) recommended during bortezomib 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
- 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
- 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
VMP
VMP: Velcade, Melphalan, Prednisone
Regimen #1, San Miguel, et al. 2008 & Bringhen, et al. 2010
- Bortezomib (Velcade) 1.3 mg/m2 IV bolus once daily on days 1, 4, 8, 11, 22, 25, 29, 32 of cycles 1-4; 1.3 mg/m2 IV bolus once daily on days 1, 8, 22, 29 of cycles 5-9
- Melphalan (Alkeran) 9 mg/m2 PO once daily on days 1-4
- Prednisone (Sterapred) 60 mg/m2 PO once daily on days 1-4
42-day cycles x 9 cycles
Supportive medication:
- Bisphosphonate given to patients with myeloma-associated bone disease unless contraindicated (only mentioned in San Miguel, et al. 2008)
Regimen #2, Bringhen, et al. 2010 - weekly bortezomib
- Bortezomib (Velcade) 1.3 mg/m2 IV bolus once daily on days 1, 8, 15, 22
- Melphalan (Alkeran) 9 mg/m2 PO once daily on days 1-4
- Prednisone (Sterapred) 60 mg/m2 PO once daily on days 1-4
35-day cycles x 9 cycles
Regimen #3, Gasparetto, et al. 2010 - "Short-course" bortezomib
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 4, 8, 11
- Melphalan (Alkeran) 6 mg/m2 PO once daily on days 1-7, given at least 1 hour prior to bortezomib
- Prednisone (Sterapred) 60 mg/m2 PO once daily on days 1-7
28-day cycles x up to 6 cycles; treatment could be given beyond 6 cycles at investigator discretion
Supportive medications:
- Bisphosphonates and Acyclovir (Zovirax) recommended
Regimen #4, Mateos, et al. 2010
Induction therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 4, 8, 11, 22, 25, 29, 32
- Melphalan (Alkeran) 9 mg/m2 PO once daily on days 1-4
- Prednisone (Sterapred) 60 mg/m2 PO once daily on days 1-4
42-day cycle x 1 cycle, then
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 8, 15, 22
- Melphalan (Alkeran) 9 mg/m2 PO once daily on days 1-4
- Prednisone (Sterapred) 60 mg/m2 PO once daily on days 1-4
35-day cycles x 5 cycles, then
Maintenance therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily 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 daily
3-month cycles x up to 3 years
Supportive medications:
- "Patients with bone disease received bisphosphonates, and prophylactic aciclovir was recommended."
- Patients receiving thalidomide needed to have thromboprophylaxis with either aspirin or low molecular weight heparin
References
- 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
- 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
- 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
VTD
VTD: Velcade (bortezomib), Thalidomide, Dexamethasone
2012: Phase III Improved PFS Increased toxicity
Regimen #1, Cavo, et al. 2010 & Cavo, et al. 2012 - GIMEMA
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 4, 8, 11
- Thalidomide (Thalomid) 100 mg PO once daily on days 1-14 of cycle 1; 200 mg PO once daily on days 15-21 of cycle 1; 200 mg PO once daily on days 1-21 of cycles 2 & 3
- Dexamethasone (Decadron) 40 mg PO once daily on days 1, 2, 4, 5, 8, 9, 11, 12
21-day cycles x 3 cycles, then
- Melphalan (Alkeran) 200 mg/m2 once on day -2
- Autologous stem cell rescue
Wait until count recovery, then
- Thalidomide (Thalomid) 100 mg PO once daily
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4
28-day cycles for 3-6 months, then
- Melphalan (Alkeran) 200 mg/m2 once on day -2
- Autologous stem cell rescue
Wait until 3 months after second transplant, then
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 8, 15, 22
- Thalidomide (Thalomid) 100 mg PO once daily
- Dexamethasone (Decadron) 40 mg PO once daily on days 1, 2, 8, 9, 15, 16, 22, 23
35-day cycles x 2 cycles, then
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4
28-day cycles, given until progression, relapse, or undue toxicity
Supportive medications:
- Acyclovir (Zovirax) prophylaxis recommended
Regimen #2, Kaufman, et al. 2010
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 4, 8, 11
- Thalidomide (Thalomid) 100 mg PO once daily on days 1-21
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 9-12
21-day cycles x 3-4 cycles
Supportive medications:
- Aspirin prophylaxis to decrease risk of DVTs
- Prophylactic "treatment with antiviral and antibiotic medications"
Regimen #3, Rosiñol, et al. 2012 - PETHEMA/GEM
- Bortezomib (Velcade) 1.3 mg/m2 once daily on days 1, 4, 8, 11
- Thalidomide (Thalomid) 50 mg PO once daily on days 1-14 of cycle 1; 100 mg PO once daily on days 15-28 of cycle 1; 200 mg PO once daily on days 1-28 of cycle 2 and thereafter
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 9-12
28-day cycles x 6 cycles
Supportive Medications:
- Low molecular weight heparin (LMWH) or aspirin recommended
References
- 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
- 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
VTD-PACE
VTD-PACE: Velcade, Thalidomide, Dexamethasone, Platinum (cisplatin), Adriamycin (doxorubicin), Cyclophosphamide, Etoposide
Regimen
This is the induction and consolidation regimen as described in Total Therapy 3. See paper for more specific regimen details, including interim thalidomide/dexamethasone dosing.
- Bortezomib (Velcade) 1.0 mg/m2 SC once daily on days 1, 4, 8, 11
- Thalidomide (Thalomid) 200 mg PO once daily on days 4-7
- Dexamethasone (Decadron) 40 mg PO once daily on days 4-7
- Cisplatin (Platinol) 10 mg/m2/day (total dose per cycle: 40 mg/m2) IV continuous infusion over 4 days on days 4-7
- Doxorubicin (Adriamycin) 10 mg/m2/day (total dose per cycle: 40 mg/m2) IV continuous infusion over 4 days on days 4-7
- Cyclophosphamide (Cytoxan) 400 mg/m2/day (total dose per cycle: 1600 mg/m2) IV continuous infusion over 4 days on days 4-7
- Etoposide (Vepesid) 40 mg/m2/day (total dose per cycle: 160 mg/m2) IV continuous infusion over 4 days on days 4-7
2 cycles before and 2 cycles after tandem autologous stem cell transplant
References
- 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. doi:10.1053/j.seminhematol.2012.04.010. Review. link to original article PubMed
VTP
VTP: Velcade (bortezomib), Thalidomide, Prednisone
Regimen
Induction therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 4, 8, 11, 22, 25, 29, 32
- Thalidomide (Thalomid) 50 mg PO once daily on days 1-15, then 100 mg PO once daily on days 16-42
- Prednisone (Sterapred) 60 mg/m2 PO once daily on days 1-4
42-day cycle x 1 cycle, then
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 8, 15, 22
- Thalidomide (Thalomid) 100 mg PO once daily
- Prednisone (Sterapred) 60 mg/m2 PO once daily on days 1-4
35-day cycles x 5 cycles, then
Maintenance therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily 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 daily
3-month cycles x up to 3 years
Supportive medications:
- "Patients with bone disease received bisphosphonates, and prophylactic aciclovir was recommended."
- Patients receiving thalidomide 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
Post-transplant maintenance/consolidation
Lenalidomide (Revlimid) consolidation & maintenance after transplant
Regimen #1, Attal, et al. 2012
Consolidation
- Lenalidomide (Revlimid) 25 mg PO once daily on days 1-21
28-day cycles x 2 cycles, then
Maintenance therapy
- Lenalidomide (Revlimid) 10 mg PO once daily x 3 months, then increased to 15 mg PO once daily if tolerated
given until progression of disease or unacceptable toxicity, or patient choice
Supportive medications:
- "Thromboprophylaxis was not used"
Regimen #2, McCarthy, et al. 2012
Patients started therapy 100-120 days after autologous hematopoietic cell transplant (AHCT).
- Lenalidomide (Revlimid) 20 mg PO once daily; after 3 months, dose may be increased to 30 mg PO once daily 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
given until progression of disease or unacceptable toxicity
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."
References
- 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. doi: 10.1056/NEJMoa1114083. 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
Thalidomide (Thalomid) maintenance after transplant
Regimen
- Thalidomide (Thalomid) 100 mg PO once daily x 6 months, starting 3 months after autologous stem cell transplant
References
- 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
Thalidomide & Prednisone maintenance after transplant
2013: Phase III Improved PFS Decreased QOL
Regimen
- Thalidomide (Thalomid) 200 mg PO once daily
- Prednisone (Sterapred) 50 mg PO once very other day
Begin after autologous transplant, continue for four years or until disease progression
Supportive Medications: Bisphosphonates, H2-blockers, and laxatives were recommended
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. doi: 10.1182/blood-2012-09-451872. Epub 2013 Jan 7. link to original article contains protocol PubMed
VTD
VTD: Velcade (bortezomib), Thalidomide, Dexamethasone
2012: Phase III Improved PFS Increased toxicity
Regimen - GIMEMA
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 4, 8, 11
- Thalidomide (Thalomid) 100 mg PO once daily on days 1-14 of cycle 1; 200 mg PO once daily on days 15-21 of cycle 1; 200 mg PO once daily on days 1-21 of cycles 2 & 3
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 9-12
21-day cycles x 3 cycles, then
- Melphalan (Alkeran) 200 mg/m2 once on day -2
- Autologous stem cell rescue
Wait until count recovery, then
- Thalidomide (Thalomid) 100 mg PO once daily
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4
28-day cycles for 3-6 months, then
- Melphalan (Alkeran) 200 mg/m2 once on day -2
- Autologous stem cell rescue
Wait until 3 months after second transplant, then
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 8, 15, 22
- Thalidomide (Thalomid) 100 mg PO once daily
- Dexamethasone (Decadron) 40 mg PO once daily on days 1, 2, 8, 9, 15, 16, 22, 23
35-day cycles x 2 cycles, then
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4
28-day cycles until progression, relapse, or undue toxicity
Supportive medications:
- Acyclovir (Zovirax) prophylaxis recommended
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
- 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
Bortezomib (Velcade)
Regimen #1, Richardson, et al. 2003, Richardson, et al. 2005, Richardson, et al. 2007 - APEX
Richardson, et al. 2003 only described the first 8 cycles of treatment
- Bortezomib (Velcade) 1.3 mg/m2 IV bolus once daily on days 1, 4, 8, 11
21-day cycles x 8 cycles, THEN
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 8, 15, 22
35-day cycles x 3 cycles
Supportive medications (described in Richardson, et al. 2005):
- Bisphosphonate IV therapy once every 3-4 weeks unless contraindicated
Regimen #2, Moreau, et al. 2011 - Subcutaneous vs. intravenous Bortezomib (Velcade) +/- Dexamethasone
- Bortezomib (Velcade) 1.3 mg/m2 SC/IV once daily 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
- IV injections are 1 mg/mL (3.5 mg bortezomib reconstituted in 3.5 mL NS), given IV push over 3-5 seconds
- 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 daily on days 1, 2, 4, 5, 8, 9, 11, 12
21-day cycles x 8-10 cycles
Supportive medications:
- Bisphosphonates "according to established guidelines"
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
- 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
- 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
- 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):431-40. Epub 2011 Apr 18. link to original article contains verified protocol PubMed
Bortezomib (Velcade) & Doxorubicin liposomal (Doxil)
Regimen
- Bortezomib (Velcade) 1.3 mg/m2 IV bolus once daily 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
21-day cycles x up to 8 cycles, given until progression of disease, or unacceptable toxicity; treatment could be continued beyond 8 cycles if it was tolerated
Supportive medications:
- "Bisphosphonates were used according to established guidelines"
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
BLD
BLD: Bendamustine, Lenalidomide, Dexamethasone
Level of Evidence: 2012 Phase II
Regimen
This study involved dose escalation. Dosages listed are the determined maximally tolerated doses (MTD).
- Bendamustine (Treanda) 75 mg/m2 IV once daily on days 1 & 2
- Lenalidomide (Revlimid) 10 mg PO once daily on days 1-21
- Dexamethasone (Decadron) 40 mg (no route specified) once per week
28-day cycles x up to 8 cycles
Supportive medications:
- Aspirin 325 mg PO once daily
- "Gastroprotectant" (H2-blocker or PPI)
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. doi: 10.1182/blood-2011-12-395715. Epub 2012 Mar 26. link to original article contains verified protocol PubMed
Carfilzomib (Kyprolis)
Level of Evidence: 2012 Phase II
Regimen
- Carfilzomib (Kyprolis) 20 mg/m2 (body surface area capped at 2.2 m2) IV over 2-10 minutes once daily on days 1-2, 8-9, 15-16 of cycle 1; then on subsequent cycles, Carfilzomib (Kyprolis) 27 mg/m2 (body surface area capped at 2.2 m2) IV over 2-10 minutes once daily 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%."
28-week cycles x up to 12 cycles, given until progression of disease or unacceptable toxicity
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."
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
- 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
- Carfilzomib (Kyprolis) package insert
DCEP
DCEP: Dexamethasone, Cyclophosphamide, Etoposide, Platinol
Regimen
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 daily on days 1-4
- Cyclophosphamide (Cytoxan) 400 mg/m2/day (total dose per cycle: 1600 mg/m2) IV continuous infusion over 4 days on days 1-4
- Etoposide (Vepesid) 40 mg/m2/day (total dose per cycle: 160 mg/m2) IV continuous infusion over 4 days on days 1-4
- Cisplatin (Platinol) 15 mg/m2/day (total dose per cycle: 60 mg/m2) IV continuous infusion over 4 days on days 1-4
28-day cycles
Supportive medications:
- G-CSF SC once daily, starting on day 5, to continue until neutrophil recovery
References
- 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):41-4. PubMed
PD
PD: Pomalidomide, Dexamethasone
Regimen - IFM 2009-02
- Pomalidomide (Pomalyst) 4 mg PO once daily on days 1-21
- Dexamethasone (Decadron) 40 mg PO once per week (e.g. on days 1, 8, 15, 22)
28-day cycles, given until disease progression
Supportive medications:
- Thromboprophylaxis "at the physician's discretion"
- G-CSF allowed beginning with cycle 2 and on
References
- 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. Blood. 2013 Jan 14. [Epub ahead of print] link to original article contains verified protocol PubMed
- Pomalidomide (Pomalyst) package insert
RD
RD: Revlimid, Dexamethasone
Regimen, Dimopoulos, et al. 2007; Weber, et al. 2007
- Lenalidomide (Revlimid) 25 mg PO once daily on days 1-21
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4, 9-12, 17-20 of cycles 1-4; 40 mg PO once daily on days 1-4 of cycle 5 and thereafter
28-day cycles
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
TD
TD: Thalidomide, Dexamethasone
Regimen, Hjorth, et al. 2012
- Thalidomide (Thalomid) 50 mg PO once daily, increased by 50 mg every 3 weeks to a maximum of 200 mg PO once daily "unless sufficient response was achieved by a lower dose"
- Dexamethasone (Decadron) 40 mg PO once daily on days 1-4
21-day cycles, to be continued until progression or best response, which would then be followed by 1–2 additional cycles
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."
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. doi: 10.1111/j.1600-0609.2012.01775.x. Epub 2012 Mar 30. link to original article contains verified protocol PubMed
VD
VD: Velcade, Dexamethasone
Regimen #1, Fukushima, et al. 2011 - weekly bortezomib
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 8, 15, 22
- Dexamethasone (Decadron) 20 mg PO/IV once daily 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
Regimen #2, Hjorth, et al. 2012
- Bortezomib (Velcade) 1.3 mg/m2 IV once daily on days 1, 4, 8, 11
- Dexamethasone (Decadron) 20 mg PO once daily on days 1, 2, 4, 5, 8, 9, 11, 12
21-day cycles, to be continued until progression or best response, which would then be followed by 1–2 additional cycles
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."
References
- 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. doi: 10.1111/j.1600-0609.2012.01775.x. Epub 2012 Mar 30. link to original article contains verified protocol PubMed
VMPT
VMPT: Velcade, Melphalan, Prednisone, Thalidomide
Regimen #1, Palumbo, et al. 2007
- Bortezomib (Velcade) 1.0-1.3 mg/m2 IV bolus once daily on days 1, 4, 15, 22
- Melphalan (Alkeran) 6 mg/m2 PO once daily on days 1-5
- Prednisone (Sterapred) 60 mg/m2 PO once daily on days 1-5
- Thalidomide (Thalomid) 50 mg PO once daily on days 1-35
35-day cycles x 6 cycles
Regimen #2, Bringhen, et al. 2010 - weekly bortezomib
- Bortezomib (Velcade) 1.3 mg/m2 IV bolus once daily on days 1, 8, 15, 22
- Melphalan (Alkeran) 9 mg/m2 PO once daily on days 1-4
- Prednisone (Sterapred) 60 mg/m2 PO once daily on days 1-4
- Thalidomide (Thalomid) 50 mg PO once daily on days 1-42
35-day cycles x 9 cycles, then
Maintenance therapy:
- Bortezomib (Velcade) 1.3 mg/m2 IV bolus once on day 1
- Thalidomide (Thalomid) 50 mg PO once daily on days 1-14
14-day cycles x 2 years or until disease progression or relapse
Regimen #3, Bringhen, et al. 2010
- Bortezomib (Velcade) 1.3 mg/m2 IV bolus once daily on days 1, 4, 8, 11, 22, 25, 29, 32 of cycles 1-4; 1.3 mg/m2 IV bolus once daily on days 1, 8, 22, 29 of cycles 5-9
- Melphalan (Alkeran) 9 mg/m2 PO once daily on days 1-4
- Prednisone (Sterapred) 60 mg/m2 PO once daily on days 1-4
- Thalidomide (Thalomid) 50 mg PO once daily on days 1-42
42-day cycles x 9 cycles, then
Maintenance therapy:
- Bortezomib (Velcade) 1.3 mg/m2 IV bolus once on day 1
- Thalidomide (Thalomid) 50 mg PO once daily on days 1-14
14-day cycles x 2 years or until disease progression or relapse
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
- 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