Biology and treatment of myeloma

New strategies for the treatment of multiple myeloma, particularly high-dose therapy with peripheral blood stem cell transplantation, can achieve complete response in up to 50% of cases. The patient's condition eventually relapses because transplantation does not completely eliminate myeloma. Posttreatment interferon may prolong responses achieved by transplantation or chemotherapy, but it does not necessarily prolong survival. New approaches are being developed to further eliminate myeloma cells after an incomplete response achieved by transplantation or other chemotherapy. These approaches aim at myeloma cell surface antigens, T-cell immunity, and biological mechanisms of myeloma growth and dissemination. Biological targets include interleukin-6 (the central myeloma growth factor), interleukin-1 beta (an amplifier of stromal and bone cell production of interleukin-6), and serum soluble interleukin-6 receptor (an enhancer of myeloma cell response to interleukin-6). Efforts to eliminate circulating myeloma cells from peripheral blood stem cell harvests use positive selection or purging to provide a product that will engraft only normal stem cells, not myeloma cells. Multidrug resistance, a major factor in treatment failure, can be reversed by agents that inhibit the multidrug resistance protein on the myeloma cell surface. Finally, expanded knowledge of biologic mechanisms has led to the development of new prognostic factors. These aim to identify patients in clinical trials who can benefit from treatment regimens designed to overcome their impact on survival. Translating new biological advances into treatment programs is essential to improving therapy for patients with myeloma.