Treatment of Multiple Myeloma
Bart Barlogie, John Shaughnessy, Guido Tricot, Joth Jacobson, Maurizio Zangari, Elias Anaissie, Ron Walker, and John Crowley
Blood 103:20–32, January 2004

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Autologous peripheral blood stem cell (PBSC)–supported high-dose melphalan is now considered standard therapy for myeloma, at least for younger patients. The markedly reduced toxicity of allotransplants using nonmyeloablative regimens (mini-allotransplantations) may hold promise for more widely exploiting the well-documented graft-versus-myeloma (GVM) effect. New active drugs include immunomodulatory agents, such as thalidomide and CC-5013 (Revimid; Celgene, Warren, NJ), and the proteasome inhibitor, PS 341 (Velcade; Millenium, Cambridge, MA), all of which not only target myeloma cells directly but also exert an indirect effect by suppressing growth and survival signals elaborated by the bone marrow microenvironment’s interaction with myeloma cells. Among the prognostic factors evaluated, cytogenetic abnormalities (CAs), which are present in one third of patients with newly diagnosed disease, identify a particularly poor prognosis subgroup with a median survival not exceeding 2 to 3 years. By contrast, in the absence of CAs, 4-year survival rates of 80% to 90% can be obtained with tandem autotransplantations. Fundamental and clinical research should, therefore, focus on the molecular and biologic mechanisms of treatment failure in the high-risk subgroup.

• Introduction
• Historical review of myeloma therapy: the first 30 years
  • Emergence of high-dose melphalan as standard therapy
  • Salvage treatment
• Advances in myeloma treatment: the past 10 years
  • Controlled clinical trials of dose intensity versus standard therapy
  • Prognostic factors with high-dose therapy
  • New agents
    • Thalidomide
    • CC-5013 (Revimid)
    • PS 341 (Velcade)
    • Other agents
  • Gene expression profiling after in vivo drug exposure
  • Allogeneic transplantations
  • Immunotherapy
  • Bone-targeting modalities
• Special clinical scenarios
  • High host risk: the elderly and patients with renal failure
  • Primary AL amyloidosis and immunoglobulin deposition disease
  • Solitary plasmacytomas of bone and extramedullary sites
  • MGUS and smoldering multiple myeloma
  • Anemia
  • Hyperviscosity syndrome
  • Immunosuppression and infections
• Current issues
• Summary and Conclusions
• References

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