Intensive treatment strategies in multiple myeloma

Intensive therapy regimens, followed by autologous (ABMT) or allogeneic bone marrow transplantation, have improved the prognosis of multiple myeloma (MM) over the last decade. However, although these regimens increase the overall response rate and survival, they are not curative, since most patients relapse after 1.5 to 3 years. The most active drug in high-dose therapy of MM is melphalan at doses of 140 mg/m2 or higher. Allogeneic bone marrow transplantation appears to be more effective than ABMT, but is not applicable in the majority of patients and is complicated by a very high toxicity rate. New clinical strategies aimed at improving the results of ABMT have been tested in phase I-II trials. The use of peripheral blood stem cell (PBSC) transplantations has allowed a reduction in the toxicity of high-dose regimens, but has not led to an increase in the overall response rate or survival. Likewise, the application of double transplants appears to improve the response rate in some patients, but has not resulted in an increase in survival. Studies testing the role of positive- or negative- selection procedures to deplete the graft of contaminating myeloma cells are still in early phases. Whether these novel clinical approaches will improve the response to high-dose therapy in MM will be defined by several ongoing phase III studies.