Current Treatment Options in Oncology

, Volume 2, Issue 3, pp 261–269 | Cite as

Relapsed multiple myeloma

  • Sandeep Pandit
  • David H. Vesole

Opinion statement

The treatment of relapsed multiple myeloma remains a challenge for clinicians. Most salvage therapies result in transient responses, with median survival from relapseranging from 6 to 18 months. No randomized trials comparing salvage therapies have been performed. In the absence of a “gold standard” salvage therapy, relapsed patients should be considered for clinical trials.

In light of the recent observation that thalidomide alone brings about a 30% to 35% response rate with manageable toxicities, this is the most promising single agent available to treat relapsed disease. The maximum effective dose appears to be {dy400} mg/d; virtually all responses are evident within 2 months of starting therapy. Combination therapy of thalidomide with pulse dexamethasone or other chemotherapeutic agents has shown promise in pilot trials. Even with thalidomide-responsive disease, the response duration is brief, ranging from 3 to 6 months. Therefore, the authors recommend that patients under the age of 78 years who have acceptable physiologic organ function, chemotherapy-sensitive disease, third-party financial coverage, and adequate hematopoietic stem cells be considered for high-dose therapy with autologous hematopoietic stem cell transplant. High-dose therapy with hematopoietic stem cell transplant provides the highest response rate, response duration, and survival compared with historical controls treated with conventional therapy. Patients under the age of 70 years who have human leukocyte antigen-compatible donors should be considered for immune-based therapy using nonmyeloablative preparative regimens with allogeneic hematopoietic stem cell transplant.


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References and Recommended Reading

  1. 1.
    Bergsagel DE: The role of chemotherapy in the treatment of multiple myeloma. Baillieres Clin Haematol 1995, 8:783–794.PubMedCrossRefGoogle Scholar
  2. 2.
    Alexanian R, Barlogie B, Tucker S: VAD-based regimens as primary treatment for multiple myeloma. Am J Hematol 1990, 33:86–89.PubMedCrossRefGoogle Scholar
  3. 3.
    Rajkumar SV, Hayman S, et al.: Thalidomide plus dexamethasone and thalidomide alone as first line treatment for newly diagnosed myeloma. Blood 2000, 96;722.Google Scholar
  4. 4.
    Pavlovsky S, Saslavsky J, Tezanos DM, et al.: A randomized trial of Melphalan and Prednisone versus melphalan, prednisone, cyclophosphamide, CCNU, and vincristine in untreated multiple myeloma. J Clin Oncol 1984, 2:836–840.PubMedGoogle Scholar
  5. 5.
    Divanen TM, for the Finnish Leukemia Group: Plateau phase in multiple myeloma: an analysis of long-term follow-up of 432 patients. Br J Haematol 1996, 92:834–839.CrossRefGoogle Scholar
  6. 6.
    Joshua DE, Brown RD, Gibson J: Multiple myeloma: why does the disease escape from plateau phase? Br J Haematol 1994, 88:667–671.PubMedGoogle Scholar
  7. 7.
    Belch A, Shelley W, Bergsagel D, et al.: A randomized trial of maintenance versus maintenance melphalan and prednisone in responding multiple myeloma patients. Br J Cancer 1988, 57:94–99.PubMedGoogle Scholar
  8. 8.
    Westin J, Rodjer S, Turesson I, et al.: IFN alpha-2b versus no maintenance treatment during the plateau phase in multiple myeloma: a randomized study. Br J Haematol 1995, 89:561–568.PubMedGoogle Scholar
  9. 9.
    Browman GP, Bergsagel DE, Sicheri D, et al.: Randomized trial of IFN maintenance in multiple myeloma: a study of the Canada Clinical Trials group. J Clin Oncol 1995, 13:2354–2360.PubMedGoogle Scholar
  10. 10.
    Attal M, Harousseau JL, Stoppa AM, et al.: A prospective randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med 1996, 335:91–97.PubMedCrossRefGoogle Scholar
  11. 11.
    Barlogie B, Jagannath S, Vesole DH, et al.: Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma. Blood 1997, 89:789–793. Nonrandomized study demonstrating the superiority of tandem transplant to conventional therapy.PubMedGoogle Scholar
  12. 12.
    Blade J, San Miguel JF, Fontanillas M, et al.: Survival of multiple myeloma patients who are potential candidates for early high-dose treatment intensification/ autotransplantation and who were conventionally treated. J Clin Oncol 1996, 14:2167–2173.PubMedGoogle Scholar
  13. 13.
    Barlogie B, Jagannath S, Desikan KR, et al.: Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood 1999, 93:55–65.PubMedGoogle Scholar
  14. 14.
    Attal MM, Harousseau JJ, Facon TT, et al.: Single versus double transplantation in myeloma: a prospective randomized trial of the Inter Groupe Francophone du Myeloma (IFM) [abstract]. Blood 2000, 96:2393.Google Scholar
  15. 15.
    Vescio R, Schiller G, Stewart AK, et al.: Multicenter phase III trial to evaluate CD34(+) selected versus unselected autologous peripheral blood progenitor cell transplantation in multiple myeloma. Blood 1999, 93:1858–1868.PubMedGoogle Scholar
  16. 16.
    Cunningham D, Powles R, Malpas J, et al.: A randomized trial of maintenance interferon following highdose chemotherapy in multiple myeloma. Long term followup results. Br J Haematol 1998, 102:495–502.PubMedCrossRefGoogle Scholar
  17. 17.
    Desikan R, Fassas A, Munshi N, et al.: Intensive consolidation therapy after tandem transplants further improves the outcome of multiple myeloma patients [abstract]. Blood 2000, 96:730.Google Scholar
  18. 18.
    Gahrton G, Svensson H, Cavo M, et al.: Paper presented at VII International Multiple Myeloma Workshop. Allogeneic and syngeneic transplantation in multiple myeloma. September 1–5, 1999. Stockholm, Sweden.Google Scholar
  19. 19.
    Giralt S, Weber D, Aleman A, et al.: Non-myeloablative conditioning with Fludarabine/Melphalan (FM) for patients with multiple myeloma [abstract]. Blood 1999, 94:1549.Google Scholar
  20. 20.
    Lalancette M, Rezvani K, Szydlo R, et al.: Excellent outcome of non-myeloablative stem cell transplant (NMSCT) for good risk multiple myeloma: the EBMT experience [abstract]. Blood 2000, 96:872.Google Scholar
  21. 21.
    Paccagnella A, Chiarion-Sileni V, Soesan M, et al.:Second and third responses to the same induction regimen in relapsing patients with multiple myeloma. Cancer 1991, 68:975.PubMedCrossRefGoogle Scholar
  22. 22.
    Barlogie B, Smith L, Alexanian R, et al.: Effective treatment of advanced multiple myeloma refractory to alkylating agents. N Engl J Med 1984, 310:1353–1356.PubMedCrossRefGoogle Scholar
  23. 23.
    Dalton WS, Jove R: Drug resistance in multiple myeloma: approaches to circumvention. Semin Oncol 1999, 26(suppl):23–27.PubMedGoogle Scholar
  24. 24.
    Dhodapkar MV, Singh J, Mehta J, et al.: Antimyeloma activity of pamidronate in vivo. Br J Haematol 1998, 103:530–532.PubMedCrossRefGoogle Scholar
  25. 25.
    Berenson JR, Lichtenstein A, Porter L, et al.: Long-term pamidronate treatment of advanced multiple myeloma reduces skeletal events. J Clin Oncol 1998, 16:593–602. This is the a priori article proving the importance of bisphosphonates in multiple myeloma.PubMedGoogle Scholar
  26. 26.
    Vacca A, Ribatti D, Roncali L, et al.: Bone marrow angiogenesis and progression in multiple myeloma. Br J Haematol 1994, 87:503–508.PubMedGoogle Scholar
  27. 27.
    Singhal S, Mehta J, Barlogie B, et al.: Anti-tumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999, 341:1565–1571. This key study proved the efficacy of thalidomide in refractory myeloma.PubMedCrossRefGoogle Scholar
  28. 28.
    Rajkumar SV, Timm MM, Go R, et al.: 2-Methoxyestradiol (2ME2) induces cell cycle arrest and apoptosis in myeloma and inhibits angiogenesis in the rat aortic ring assay: results of preclinical studies [abstract]. Blood 2000, 96:1557.Google Scholar
  29. 29.
    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. A cooperative group study showing superior outcome of autologous transplant as salvage therapy. Results were superior to historical control studies using conventional treatments.PubMedGoogle Scholar
  30. 30.
    Rajkumar SV, Fonseca R, Gertz MA, et al.: Autologous stem cell transplantation for relapsed and primary multiple myeloma. Bone Marrow Transplant 1999, 23:1267–1272.PubMedCrossRefGoogle Scholar
  31. 31.
    Tricot G, Jagannath S, Vesole DH, et al.: Relapse of multiple myeloma after autologous transplantation: survival after salvage therapy. Bone Marrow Transplant 1995, 16:7–11.PubMedGoogle Scholar
  32. 32.
    Morris TCM, Svebsson H, Bjorkstrand B, et al.: If double PBSC transplants have a role in myeloma when are they best performed? An EBMT Registry study [abstract]. Blood 2000, 96:3447.Google Scholar
  33. 33.
    Lokhorst HM, Schattenberg A, Cornelissen JJ, et al.:Donor leukocyte infusions for relapsed multiple myeloma after allogeneic stem-cell transplantation: predictive factors for response and long-term outcome. J Clin Oncol 2000, 18:3031–3037. The use of donor leukocyte infusions can induce a graft-versusmyeloma effect after relapse from allogeneic transplant.PubMedGoogle Scholar
  34. 34.
    Alyea EP, Soiffer RJ, Ritz J, et al.: Toxicity and efficacy of defined doses of CD4+ donor lymphocytes for treatment of relapse after allogeneic bone marrow transplant. Blood 1998, 91:3671–3680.PubMedGoogle Scholar
  35. 35.
    Stinchcombe TE, Mitchell BS, Depcik-Smith N, et al.:PS-341 is active in multiple myeloma: preliminary report of a phase I trial of the Proteasome inhibitor PS-341 in patients with hematologic malignancies [abstract]. Blood 2000, 98:2219.Google Scholar
  36. 36.
    Hussein MA, Karam MA, McLain DA, et al.: Biologic and clinical evaluation of Rituxan in the management of newly diagnosed multiple myeloma [abstract]. Blood 1999, 94:1400.Google Scholar
  37. 37.
    Bataille R, Barlogie B, Lu ZY, et al.: Biologic effects of anti-interleukin-6 murine monoclonal antibody in advanced multiple myeloma. Blood 1995, 86:685–691.PubMedGoogle Scholar
  38. 38.
    Munshi N, Desikan R, Zangari M, et al.: Marked antitumor effect of arsenic trioxide in high risk refractory multiple myeloma [abstract]. Blood 1999, 96:541.Google Scholar
  39. 39.
    Vesole DH, Kornbluth J, Jagannath S, et al.: Biological response modifiers in refractory multiple myeloma: lack of clinical efficacy of recombinant human interleukin-4 and all-trans retinoic acid (ATRA). Blood 1993, 82:263a.Google Scholar
  40. 40.
    Trivedi E, Al-Katib A, Murgo B, et al.: Phase II clinical evaluation of Bryostatin-1 in patients with relapsed multiple myeloma [abstract]. Blood 1999, 96:4635.Google Scholar

Copyright information

© Current Science Inc 2001

Authors and Affiliations

  • Sandeep Pandit
    • 1
  • David H. Vesole
    • 1
  1. 1.Division of Hematology/OncologyMedical College of WisconsinMilwaukeeUSA

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