Current Treatment Options in Oncology

, Volume 4, Issue 3, pp 229–237

Treatment of relapsed and refractory multiple myeloma

  • Seema Singhal
  • Jayesh Mehta
Article

Opinion statement

The definition of relapsed and refractory myeloma was straightforward when melphalanprednisone constituted the mainstay of treatment and high-dose therapy with transplantation was rarely used in myeloma. However, several advances have occurred in the treatment of myeloma over the past decade. Most notably, high-dose therapy and transplantation have become broadly applicable, thalidomide has become available as effective salvage therapy, and several investigational agents with novel mechanisms of action appear to be very promising. Because of the differing properties of some of these agents, it is often possible to control the disease with an alternative treatment approach after the failure of one therapy. Some data indicate that combinations of these agents work when the drugs have failed individually. Therefore, refractory myeloma indicates disease unresponsive to the most recent therapy administered. Broadly, the salvage approaches that are used in patients with refractory or relapsed disease include high-dose dexamethasone, high-dose chemotherapy with autotransplantation, allogeneic hematopoietic stem cell transplantation, thalidomide-based therapies, and novel/ investigational agents. The appropriate therapy for a given situation depends on the nature of the disease, age, organ function, bone marrow function, prior treatment, the availability of stem cell donors, and access to novel agents. A therapeutic trial of thalidomide is essential at some stage of the disease in all patients. High-dose therapy with autotransplantation is needed at some stage of the disease in most patients younger than 65 to 70 years.

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References and Recommended Reading

  1. 1.
    Singhal S: High-dose therapy and autologous transplantation. In Myeloma. Edited by Mehta J, Singhal S. London: Martin Dunitz; 2002:327–347.Google Scholar
  2. 2.
    Mehta J: Allogeneic hematopoietic stem cell transplantation in myeloma. In Myeloma. Edited by Mehta J, Singhal S. London: Martin Dunitz; 2002:349–365.Google Scholar
  3. 3.
    Powles R, Singhal S, Sirohi B, et al.: Discontinuous complete remission: a new endpoint to evaluate the success of therapy in keeping myeloma patients disease-free for extended periods of time [abstract]. Blood 2001, 98:166a.Google Scholar
  4. 4.
    Powles R, Sirohi B, Treleaven J, et al.: Continued first complete remission in multiple myeloma for over 10 years: a series of “operationally cured” patients [abstract]. Blood 2000, 96(Suppl 1):515a.Google Scholar
  5. 5.
    Zomas A, Dimopoulos MA: Conventional treatment of myeloma. In Myeloma. Edited by Mehta J, Singhal S. London: Martin Dunitz; 2002:313–326.Google Scholar
  6. 6.
    Singhal S, Mehta J, Desikan R, et al.: Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999, 341:1565–1571. The first description of the activity of thalidomide in patients with myeloma.PubMedCrossRefGoogle Scholar
  7. 7.
    Singhal S, Mehta J: Thalidomide in cancer. Biomed Pharmacother 2002, 56:4–12. A comprehensive review of the mechanisms of action of thalidomide and its use in patients with cancer.PubMedCrossRefGoogle Scholar
  8. 8.
    Desikan R, Siegel D, Anaissie E, et al.: Peripheral blood stem cell (PBSC) mobilization with DCEP, an effective regimen for high risk multiple myeloma (MM) and prompt engraftment after melphalan (MEL 200 mg/m2)-based high dose therapy [abstract]. Blood 1998, 92(Suppl 1):273a.Google Scholar
  9. 9.
    Lee CK, Barlogie B, Zangari M, et al.: D.T. PACE, a new effective angio-chemotherapy for patients with previously treated myeloma [abstract]. Blood 2002, 100:3231.Google Scholar
  10. 10.
    Powles R, Sirohi B, Singhal S, et al.: Using the original infusional induction chemotherapy again as salvage therapy in myeloma patients relapsing after one autograft [abstract]. Blood 2001, 98:165a.CrossRefGoogle Scholar
  11. 11.
    Mehta J, Singhal S: Graft versus myeloma. Bone Marrow Transplant 1998, 22:835–843. A comprehensive review of immunologic graft-versus-tumor effects in myeloma allografts.PubMedCrossRefGoogle Scholar
  12. 12.
    Barlogie B, Tricot G, Anaissie E, et al.: Long-term followup (median of 4 yrs) of 169 patients receiving thalidomide (THAL) for advanced and refractory multiple myeloma (MM): superior survival in the absence of cytogenetic abnormalities (CA) and low b-2 microglobulin (B2M) [abstract]. Blood 2002, 100:789.Google Scholar
  13. 13.
    Singhal S, Mehta J: Novel therapies in multiple myeloma. Int J Hematol 2003, in press. A comprehensive review of the mechanisms of action of thalidomide and its use in patients with myeloma.Google Scholar
  14. 14.
    Kelleher P, Chapel H: Infections: principles of prevention and therapy. In Myeloma. Edited by Mehta J, Singhal S. London: Martin Dunitz; 2002:223–239.Google Scholar
  15. 15.
    Shrieve DC: The role of radiotherapy. In Myeloma. Edited by Mehta J, Singhal S. London: Martin Dunitz; 2002:367–381.Google Scholar
  16. 16.
    Dispenzieri A, Wiseman G, Lacy MQ, et al.: A phase I/II dose escalation study of 153-Samarium EDTMP (153-Sm-EDMTP) with fixed dose melphalan peripheral stem cell transplantation (PBSCT) for multiple myeloma (MM) [abstract]. Blood 2001, 98:2855.Google Scholar
  17. 17.
    Giralt S, Bensinger W, Goodman M, et al.: Long-term follow-up of 83 patients with multiple myeloma (MM) treated on a phase I-II study of skeletal targeted radiotherapy (STR) using 166Ho-DOTMP plus melphalan with or without total body irradiation (TBI) and autologous hematopoietic stem cell transplant (AHSCT) [abstract]. Blood 2002, 100:670.Google Scholar
  18. 18.
    Dimopoulos MA, Hester J, Huh Y, et al.: Intensive chemotherapy with blood progenitor transplantation for primary resistant multiple myeloma. Br J Haematol 1994, 87:730–734.PubMedGoogle Scholar
  19. 19.
    Alexanian R, Dimopoulos MA, Hester J, et al.: Early myeloablative therapy for multiple myeloma. Blood 1994, 84:4278–4282.PubMedGoogle Scholar
  20. 20.
    Singhal S, Powles R, Sirohi B, et al.: Response to induction chemotherapy is not essential to obtain survival benefit from high-dose melphalan and autotransplantation in myeloma. Bone Marrow Transplant 2002, 30:673–679.PubMedCrossRefGoogle Scholar
  21. 21.
    Vesole DH, Crowley JJ, Catchatourian R, et al.: Highdose melphalan with autotransplantation for refractory multiple myeloma: results of a Southwest Oncology Group phase II trial. J Clin Oncol 1999, 17:2173–2179.PubMedGoogle Scholar
  22. 22.
    Rajkumar SV, Fonseca R, Lacy MQ, et al.: Autologous stem cell transplantation for relapsed and primary refractory myeloma. Bone Marrow Transplant 1999, 23:1267–1272.PubMedCrossRefGoogle Scholar
  23. 23.
    Desikan R, Barlogie B, Sawyer J, et al.: Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities. Blood 2000, 95:4008–4010. The largest reported series of autotransplantation in patients with myeloma.PubMedGoogle Scholar
  24. 24.
    Sirohi B, Powles R, Singhal S, et al.: 200 mg/m2 melphalan (HDM200) and salvage autotransplantation in myeloma patients relapsing after a preceding autograft [abstract]. Blood 2002, 100:1680.Google Scholar
  25. 25.
    Mehta J, Singhal S, Desikan K, et al.: High-dose therapy and stem cell support in myeloma. In PPO Updates. Edited by De Vita VT Jr, Hellman S, Rosenberg SA. Philadelphia: Lippincott Williams & Wilkins; 1999, 13:1–12.Google Scholar
  26. 26.
    Singhal S, Safdar A, Chiang KY, et al.: Non-myeloablative allogeneic transplantation (’microallograft’) for refractory myeloma after two preceding autografts: feasibility and efficacy in a patient with active aspergillosis. Bone Marrow Transplant 2000, 26:1231–1233.PubMedCrossRefGoogle Scholar
  27. 27.
    Badros A, Barlogie B, Morris C, et al.: High response rate in refractory and poor-risk multiple myeloma after allotransplantation using a nonmyeloablative conditioning regimen and donor lymphocyte infusions. Blood 2001, 97:2574–2579. Outcome of nonmyeloablative allografts in patients with advanced myeloma.PubMedCrossRefGoogle Scholar
  28. 28.
    Maloney DG, Sahebi F, Stockerl-Goldstein KE, et al.: Combining an allogeneic graft vs myeloma effect with high-dose autologous stem cell rescue in the treatment of multiple myeloma [abstract]. Blood 2001, 98:1822.Google Scholar
  29. 29.
    Kröger N, Schwerdtfeger R, Kiehl M, et al.: Autologous stem cell transplantation followed by a dose-reduced allograft induces high complete remission rate in multiple myeloma. Blood 2002, 100:755–760.PubMedCrossRefGoogle Scholar
  30. 30.
    Kröger N, Sayer HG, Schwerdtfeger R, et al.: Unrelated stem cell transplantation in multiple myeloma after a reduced-intensity conditioning with pretransplantation antithymocyte globulin is highly effective with low transplantation-related mortality. Blood 2002, 100:3919–3924.PubMedCrossRefGoogle Scholar
  31. 31.
    Attal M, Harousseau JL, Facon T, et al.: Double autologous transplantation improves survival of multiple myeloma patients: final analysis of a prospective randomized study of the “Intergroupe Francophone du Myelome” (IFM 94) [abstract]. Blood 2002, 100:7.Google Scholar

Copyright information

© Current Science Inc 2003

Authors and Affiliations

  • Seema Singhal
    • 1
  • Jayesh Mehta
  1. 1.Division of Hematology/OncologyThe Feinberg School of Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern UniversityChicagoUSA

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