Current drug therapy for multiple myeloma

Recent years have witnessed tremendous advances in the molecular pathogenesis and management of multiple myeloma. Standard chemotherapy (melphalan and prednisone; MP) has been the mainstay of treatment of multiple myeloma for about 3 decades. However, it is no longer considered the 'gold standard', particularly for those patients who will subsequently undergo intensive chemotherapy with autologous or allogeneic peripheral blood stem cell (PBSC) or bone marrow transplantation (BMT), or for patients with refractory myeloma. A variety of induction combination chemotherapy regimens have been developed, some of which have demonstrated an improved response rate and duration and a superior 5-year survival rate when compared with standard chemotherapy. The early use of high dose chemotherapy with autologous PBSC support or BMT has significantly increased the complete remission rate, and has prolonged event-free survival and overall survival. Allogeneic bone marrow or PBSC transplantation may be a good option for selected patients with poor prognostic features. The role of interferon-α in multiple myeloma is still inconclusive despite many years of clinical evaluation. The clinical application of chemosensitising agents that can inhibit P-glycoprotein (P-gp) expression and function, and particularly the development of more potent P-gp modulators such as valspodar (PSC 833) and elacridar (GF120918) has made it possible to reverse multidrug resistance in some refractory patients and to enhance the efficacy of chemotherapeutic agents. Immunotherapeutic approaches to purging of autologous bone marrow or PBSC, or as adjuvant therapy for minimal residual disease, show great promise. Finally, a number of new therapies specifically designed to treat many of the complications of multiple myeloma are improving clinical outcomes and quality of life for these patients.