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Initial Therapy of Multiple Myeloma in Patients who are Candidates for Stem Cell Transplantation

  • Plasma Cell Dyscrasias
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Multiple myeloma (MM), a B cell hematologic malignancy involving plasma cells, responds to a variety of drugs including alkylators, steroids, anthracyclines, immunomodulators and proteosome inhibitors. The disease, however, remains largely incurable for the majority of patients. For patients who are suitable candidates, high dose chemotherapy with autologous stem cell support (ASCT) after induction therapy has been shown to improve response rates, progression free survival and overall survival compared to conventional chemotherapy. The availability of new drugs including thalidomide, lenalidomide and bortezomib has rapidly changed induction strategies. These drugs have been combined with corticosteroids, alkylators and anthracyclines to treat front-line patients with MM. Preliminary, phase 1–2 studies have indicated very high response rates and complete response rates formerly only seen with ASCT. Emerging data from randomized trials suggest that older regimens such as vincristine, adriamycin and dexamethasone (VAD) are not as effective for induction as newer combinations. Thus new regimens incorporating novel agents should improve overall response rates, increase complete responders which should translate into improved progression free and overall survival.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: •Of importance ••Of major importance

  1. Child JA, Morgan GJ, Davies FE, et al (2003) High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 348:1875–1883. A large, randomized trial comparing conventional chemotherapy (CC) in the pre-novel agent era to CC followed by high dose therapy and stem cell transplant

    Article  PubMed  CAS  Google Scholar 

A large, randomized trial comparing conventional chemotherapy (CC) in the pre-novel agent era to CC followed by high dose therapy and stem cell transplant.

  1. Kumar S, Anderson KC (2005) Drug insight: Thalidomide as a treatment for multiple myeloma (Review). Nat Clin Pract Oncol 2:262–270

    Article  PubMed  CAS  Google Scholar 

  2. Anderson KC, Shaughnessy JD Jr., Barlogie B, et al (2002) Multiple myeloma. In: Broudy VC, Abkowitz JL, Vose JM (eds) Hematology 2002: American Society of Hematology Education Program Book. American Society of Hemtology, Washington DC, pp 214–240

    Google Scholar 

  3. Attal M, Harousseau J-L, Stoppa A-M, et al (1996) A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med 335:91–97

    Article  PubMed  CAS  Google Scholar 

  4. Lahuerta JJ, Martinez-Lopez J, Serna JD, et al (2000) Remission status defined by immunofixation vs. electrophoresis after autologous transplantation has a major impact on the outcome of multiple myeloma patients. Br J Haematol 109:438–446

    Article  PubMed  CAS  Google Scholar 

  5. Alexanian R, Weber D, Giralt S, et al (2001) Impact of complete remission with intensive therapy in patients with responsive multiple myeloma. Bone Marrow Transplant 27:1037–1043

    Article  PubMed  CAS  Google Scholar 

  6. Davies FE, Forsyth PD, Rawstron AC, et al (2001) The impact of attaining a minimal disease state after high-dose melphalan and autologous transplantation for multiple myeloma. Br J Haematol 112:814–819

    Article  PubMed  CAS  Google Scholar 

  7. Harousseau J-L, Attal M, Moreau P, et al (2006) The prognostic imapct of complete remission (CR) plus very good partial remission (VGPR) in a double-transplantation program for newly diagnosed multiple myeloma (MM). Combined results of the IFM 99 trials [abstract]. Blood 108(Part 1):877a

    Google Scholar 

  8. Wang M, Delasalle K, Thomas S, et al (2006) Complete remission represents the major surrogate marker of long survival in multiple myeloma. Blood 108(Part 1):123a–124a

    Google Scholar 

  9. Corradini P, Cavo M, Lokhorst H, et al (2003) Molecular remission after myeloablative allogeneic stem cell transplantation predicts a better relapse-free survival in patients with multiple myeloma. Blood 102:1927–1929. An important study defining the impact of minimal residual disease on outcome.

    Article  PubMed  CAS  Google Scholar 

An important study defining the impact of minimal residual disease on outcome.

  1. Durie BG, Harousseau JL, Miguel JS, et al (2006) International uniform response criteria for multiple myeloma. Leukemia 20:2220

    Article  Google Scholar 

  2. Dispenzieri A, Zhang L, Fonesca R, et al (2006) Single agent bortezomib is associated with a high response rate in patients with high risk multiple myeloma. A phase II study from the Eastern Cooperative Oncology Group (E2A02) [abstract]. Blood 108(Part 1):1006a

    Google Scholar 

  3. Macro M, Divine M, Uzunhan Y, et al (2006) Dexamethasone + thalidomide (Dex/Thal) compared to VAD as a pre-transplant treatment in newly diagnosed multiple myeloma (MM): a randomized trial [abstract]. Blood 108(Part 1):22a

    Google Scholar 

  4. Rajkumar SV, Hussein M, Catalano J, et al (2006) A randomized, double-blind, placebo-controlled trial of thalidomide plus dexamethasone versus dexamethasone alone as primary therapy for newly diagnosed multiple myeloma [abstract]. Blood 108(Part 1):238a

    Google Scholar 

  5. Ludwig H, Drach J, Tóthová E, et al (2005) Thalidomide-dexamethasone versus melphalan-prednisolone as first line treatment in elderly patients with multiple myeloma: an interim analysis [abstract]. Blood 106(Part 1):231a

    Google Scholar 

  6. Lacy M, Gertz M, Dispenzieri A, et al (2006) Lenalidomide plus dexamethasone (Rev/Dex) in newly diagnosed myeloma: response to therapy, time to progression, and survival [abstract]. Blood 108(Part 1):239a

    Google Scholar 

  7. Harousseau J-L, Marit G, Caillot D, et al (2006) VELCADE/dexamethasone (VelDex) versus VAD as inductions treatemnt prior to autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma (MM): an interim analysis of the IFM 2005-01 randomized multicenter phase III trial [abstract]. Blood 108 (Part 1):21a

    Google Scholar 

  8. Jagannath S, Durie BGM, Wolf JL, et al (2006) Long-term follow-up of patients treated with bortezomib alone and in combination with dexamethasone as frontline therapy for multiple myeloma [abstract]. Blood 108 (Part 1):238a–239a

    Google Scholar 

  9. Borrello I, Ferguson A, Huff CA, et al (2006) Boretezomib and thalidomide treatment of newly diagnosed patients with multiple myeloma - efficacy and neurotoxicity. Blood 108(Part 1): 1006a

    Google Scholar 

  10. Orlowski RZ, Peterson BL, Sanford B, et al (2006) Bortezomib and pegylated liposomal doxorubicin as induction therapy for adult patients with symptomatic multiple myeloma: Cancer and Leukemia Group B Study 10301 [abstract]. Blood 108 (Part 1):239a

    Google Scholar 

  11. Oakervee HE, Popat R, Curry N, et al (2005) PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma. Br J Haematol 129:755–762

    Article  PubMed  CAS  Google Scholar 

  12. Goldschmidt H, Sonneveld P, Breitkreuz I, et al (2005) HOVON 50/GMMG-HD3-trial: phase III study on the effect of thalidomide combined with high dose melphalan in myeloma patients up to 65 years [abstract]. Blood 106(Part 1):128a

    Google Scholar 

  13. Offidani M, Corvatta L, Piersantelli MN, et al (2006) Thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) for patients older than 65 years with newly diagnosed multiple myeloma. Blood 108:2159–2164

    Article  PubMed  CAS  Google Scholar 

  14. Wang M, Delasalle K, Giralt S, et al (2005) Rapid control of previously untreated multiple myeloma with bortezomib-thalidomide-dexamethasone followed by early intensive therapy [abstract]. Blood 106 (Part 1):231a

    Google Scholar 

  15. Niesvizky R, Jayabalan DS, Zafar F, et al (2006) Lenalidomide induced myelosuppression is potentially associated with renal dysfunction in treatment naive myeloma (MM) patients receiving BiRD (Biaxin®/Revlimid®/Dexamethasone) combination therapy (Rx) [abstract]. Blood 108(Part 1):1013a

    Google Scholar 

  16. Badros A, Rapoport A, Goloubeva O, et al (2005) Phase I trial of bortezomib (V) in combination with “DT-PACE”: toxicity, stem cell collection and engraftment in newly diagnosed multiple myeloma (MM) patients (Pts) [abstract]. Blood 106 (Part 1):771a

    Google Scholar 

  17. Zervas K, Mihou D, Katodritou I, et al (2006) VAD-doxil vs. VAD-doxil plus thalidomide as initial treatment in patients with multiple myeloma: a multicenter randomized trial of the Greek Myeloma Study Group [abstract]. Blood 108(Part 1):238a

    Google Scholar 

  18. Uy GL, Fisher NM, Devine SM, et al (2005) Bortezomib does not impair cytokine induced mobilization of stem cells prior to autologous transplantation in myeloma [abstract]. Blood 106(Part 1):821a

    Google Scholar 

  19. Bruno B, Rotta M, Patriarca F, et al (2007) A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med 356:1110–1120

    Article  PubMed  CAS  Google Scholar 

  20. Hsi ED, Steinle R, Balasa B, et al (2006) CS1: a potential new therapeutic target for the treatment of multiple myeloma [abstract]. Blood 108(Part 1):986a

    Google Scholar 

  21. Hussein MA, Berenson JR, Niesvizky R, et al (2006) Results of a phase I trial of SGN-40 (anti-huCD40mAb) inpatients with relapsed multiple myeloma [abstract]. Blood 108(Part 1):1021a

    Google Scholar 

  22. Chanan-Khan AA, Jagannath S, Schlossman RL, et al (2006) Phase I study of BB-10901 (huN901-DM1) in patients with relapsed and relapsed/refractory CD56-positive multiple myeloma [abstract]. Blood 108(Part 1):1021a

    Google Scholar 

  23. Bensinger W, Jagannath S, Becker PS, et al (2006) A phase 1 dose escalation study of a fully human antagonist anti-CD40 antibody, HCD122 (formerly CHIR-12.12) in patients with relapsed and refractory multiple myeloma [abstract]. Blood 108(Part 1):1021a

    Google Scholar 

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  1. Fred Hutchinson Cancer Research Center, D5-390 1100 Fairview Avenue N., Seattle, WA, 98118, USA

    William Bensinger M.D.

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  1. William Bensinger M.D.
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Correspondence to William Bensinger M.D..

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Bensinger, W. Initial Therapy of Multiple Myeloma in Patients who are Candidates for Stem Cell Transplantation. Curr. Treat. Options in Oncol. 8, 135–143 (2007). https://doi.org/10.1007/s11864-007-0027-z

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  • DOI: https://doi.org/10.1007/s11864-007-0027-z

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