S. Vincent Rajkumar, MD

Multiple myeloma is now the most common indication for autologous stem cell transplantation (ASCT) in North America, with over 5,000 transplants performed yearly (Center for International Blood and Marrow Transplant Research [CIBMTR] data). While the role of ASCT as initial therapy in multiple myeloma has been established by randomized studies, newer therapies are challenging the traditional paradigm. The availability of novel induction agents and newer risk stratification tools, and the increasing recognition of durability of remissions are changing the treatment paradigm. However, even with arduous therapy designed to produce more complete remissions—for example, tandem autologous transplants—we have seen no plateau in survival curves. A tandem autologous procedure followed by maintenance therapy may be performed in an attempt to sustain remission. Sequential autologous transplants followed by nonmyeloablative allotransplants are pursued with the hope of "curing" multiple myeloma. We examine how the key challenges of increasing the response rates and maintaining responses are being addressed using more effective induction and/or consolidation treatments and the need for maintenance therapies after ASCT. We argue that given the biologic heterogeneity of multiple myeloma, risk-adapted transplant approaches are warranted. While the role of curative-intent, dose-intense toxic therapy is still controversial, conventional myeloablative allogeneic transplants need to be reexamined as an option in high-risk aggressive myeloma, given improvements in supportive care and transplant-related mortality.

Standard therapy for multiple myeloma, which accounts for 10% ofall hematologic malignancies, has been autologous stem cell transplantation(ASCT), alkylator-based chemotherapy, and corticosteroids. Severaladvances have been made in the treatment of multiple myelomaover the past decade, especially the arrival of new, active agents suchas thalidomide (Thalomid), bortezomib (Velcade), and lenalidomide(Revlimid). These have shown significant clinical activity as singleagents. Trials are ongoing to incorporate these new agents into thevarious stages of treatment and to combine them with other effectivetreatment modalities, including ASCT.