Multiple myeloma

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First-line regimens (including transplant ineligible)

BiRD

BiRD: Biaxin, Revlimid, Dexamethasone

Levels of Evidence: 2013 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:

References

  1. 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
  2. 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
  3. 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

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

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:

Regimen #2, Morgan, et al. 2012 - CTD

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:

References

  1. 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
  2. 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.

21-day cycles x up to 6 cycles

Supportive medications:

References

  1. 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

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)

21-day cycles x 8 cycles, then

Maintenance therapy:

42-day cycles x 4 cycles

Supportive medications:

Regimen #3, Kumar, et al. 2012 - EVOLUTION (VDC)

21-day cycles x 8 cycles, then

Maintenance therapy:

42-day cycles x 4 cycles

Supportive medications:

References

  1. 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
  2. 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

  1. 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

  1. 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

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

4-week cycles, given until maximal response, progression of disease, or unacceptable toxicity

References

  1. 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
  2. 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

6-week cycles x 12 cycles

Regimen #2, San Miguel, et al. 2008

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.

6-week cycles

Regimen #4, Facon, et al. 2006

6-week cycles x 12 cycles

Regimen #5, Hulin, et al. 2009

6-week cycles x 12 cycles

Regimen #6, Palumbo, et al. 2012

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

28-day cycles x 8 cycles

Supportive medications:

Regimen #8, Morgan, et al. 2011 - MRC Myeloma IX study

28-day cycles x 6-9 cycles

Supportive medications:

References

  1. Kyle RA. Monoclonal gammopathy and multiple myeloma in the elderly. Baillieres Clin Haematol. 1987 Jun;1(2):533-57. PubMed
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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

28-day cycles x 9 cycles, THEN

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

28-day cycles x 9 cycles

Supportive medications:

  • Aspirin 75-100 mg PO once daily as thromboprophylaxis

References

  1. 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
  2. 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

42-day cycles x 12 cycles

Regimen #2, Palumbo, et al. 2006 & Palumbo, et al. 2008

Supportive medications:

28-day cycles x 6 cycles, then

Regimen #3, Hulin, et al. 2009

42-day cycles x 12 cycles

Regimen #4, Wijermans, et al. 2010 - HOVON 49

Induction therapy

28-day cycles x 8 cycles, then

28-day course, then

Maintenance therapy

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

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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

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):

Regimen #2, Rajkumar, et al. 2010

28-day cycles

Supportive medications:

  • One of the following bisphosphonates:
  • "Thromboprophylaxis" aspirin (80 mg or 325 mg per physician discretion) once daily as thrombosis prophylaxis.

Regimen #3, Rajkumar, et al. 2005

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

  1. 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
  2. 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
  3. 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

21-day cycles x 4-8 cycles

Supportive medications:

Patients who responded and tolerated therapy could proceed to maintenance therapy at previously tolerated dose with a different schedule:

21-day cycles

Regimen #2, Kumar, et al. 2012 - EVOLUTION

21-day cycles x 8 cycles, then

Maintenance therapy:

42-day cycles x 4 cycles

Supportive medications:

References

  1. 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
  2. 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

21-day cycles x 8 cycles, then

Maintenance therapy:

42-day cycles x 4 cycles

Supportive medications:

References

  1. 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

Levels of Evidence:

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

28-day cycles

Regimen #3, Cavo, et al. 2010 & Cavo, et al. 2012 - GIMEMA

21-day cycles x 3 cycles, then

Wait until count recovery, then

28-day cycles for 3-6 months, then

Wait until 3 months after second transplant, then

35-day cycles x 2 cycles, then

28-day cycles until progression, relapse, or undue toxicity

Supportive medications:

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

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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

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:
  • "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

21-day cycles x 4 cycles

References

  1. 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
  2. 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
  3. 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

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.

Supportive medications:

Regimen #2, Segeren, et al. 1999

4-week cycles

Supportive medications:

  • 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 #3, Berenson, et al. 2002 - prednisone maintenance

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:

Regimen #4, Dimopoulos, et al. 2003

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

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:

References

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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

21-day cycles x 4 cycles

Supportive medications:

  • One of the following bisphosphonates recommended:
  • "Antibiotics, antifungal agents, and antiviral prophylaxis in accordance with local practice."

References

  1. 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
  2. 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

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

21-day cycles x 4 cycles, THEN

Stem cell mobilization & reinfusion

Paper did not describe the full details

Consolidation

28-day cycles x 4 cycles, THEN

Maintenance

28-day cycles, given until relapsed disease

Supportive medications:

References

  1. 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
  2. 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
  3. 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

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

35-day cycles x 9 cycles

Regimen #3, Gasparetto, et al. 2010 - "Short-course" bortezomib

28-day cycles x up to 6 cycles; treatment could be given beyond 6 cycles at investigator discretion

Supportive medications:

Regimen #4, Mateos, et al. 2010

Induction therapy

42-day cycle x 1 cycle, then

35-day cycles x 5 cycles, then

Maintenance therapy

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

  1. 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
  2. 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
  3. 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
  4. 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

Levels of Evidence:

2012: Phase III Improved PFS Increased toxicity

Regimen #1, Cavo, et al. 2010 & Cavo, et al. 2012 - GIMEMA

21-day cycles x 3 cycles, then

Wait until count recovery, then

28-day cycles for 3-6 months, then

Wait until 3 months after second transplant, then

35-day cycles x 2 cycles, then

28-day cycles, given until progression, relapse, or undue toxicity

Supportive medications:

Regimen #2, Kaufman, et al. 2010

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

28-day cycles x 6 cycles

Supportive Medications:

  • Low molecular weight heparin (LMWH) or aspirin recommended

References

  1. 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
  2. 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
  3. 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
  4. 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, Barlogie, et al. 2007 - Total Therapy 3

Induction therapy

  • 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
  • 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:

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 2-6 months apart.

During the interim period after transplant 1 and transplant 2, patients receive:

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 1.5-4 months after the last transplant. Cycle 2 of consolidation starts 2-4 months after cycle 1 of consolidation.

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:

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 1-4 months after consolidation cycle 2.

28-day cycles x 1 year, then proceed to maintenance therapy years 2-3

Maintenance therapy, years 2 & 3 - DT

28-day cycles x 2 years

References

  1. 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
  2. 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
  3. 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

42-day cycle x 1 cycle, then

35-day cycles x 5 cycles, then

Maintenance therapy

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

  1. 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

28-day cycles x 2 cycles, then

Maintenance therapy

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

  1. 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
  2. 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

  1. 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

Levels of Evidence:

2013: Phase III Improved PFS Decreased QOL

Regimen

Begin after autologous transplant and give for four years or until disease progression

Supportive Medications:

  • "Bisphosphonates, histamine-2 blockers, and laxatives were recommended"
  • "Anticoagulant and antiplatelet medications were not mandated"

References

  1. 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 verified protocol PubMed

VTD

VTD: Velcade (bortezomib), Thalidomide, Dexamethasone

Levels of Evidence:

2012: Phase III Improved PFS Increased toxicity

Regimen - GIMEMA

21-day cycles x 3 cycles, then

Wait until count recovery, then

28-day cycles for 3-6 months, then

Wait until 3 months after second transplant, then

35-day cycles x 2 cycles, then

28-day cycles until progression, relapse, or undue toxicity

Supportive medications:

References

  1. 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
  2. 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

21-day cycles x 8 cycles, THEN

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

  1. 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
  2. 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
  3. 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
  4. 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

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

  1. 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).

28-day cycles x up to 8 cycles

Supportive medications:

  • Aspirin 325 mg PO once daily
  • "Gastroprotectant" (H2-blocker or PPI)

References

  1. 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

  1. 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
  2. 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
  3. 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.

28-day cycles

Supportive medications:

  • G-CSF SC once daily, starting on day 5, to continue until neutrophil recovery

References

  1. 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

[*] IFM 2009-02 also studied continuous daily dosing of pomalidomide but concluded that, given similar efficacy and toxicity, the 21 out of 28 day dosing was preferred.

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

  1. 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
  2. Pomalidomide (Pomalyst) package insert

RD

RD: Revlimid, Dexamethasone

Regimen, Dimopoulos, et al. 2007; Weber, et al. 2007

28-day cycles

References

  1. 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
  2. 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

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

  1. 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

35-day cycles, to be continued until complete response, progression of disease, or severe adverse events

Regimen #2, Hjorth, et al. 2012

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

  1. 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
  2. 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

35-day cycles x 6 cycles

Regimen #2, Bringhen, et al. 2010 - weekly bortezomib

35-day cycles x 9 cycles, then

Maintenance therapy:

14-day cycles x 2 years or until disease progression or relapse

Regimen #3, Bringhen, et al. 2010

42-day cycles x 9 cycles, then

Maintenance therapy:

14-day cycles x 2 years or until disease progression or relapse

References

  1. 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
  2. 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
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