Management of patients with multiple myeloma: emphasizing the role of high-dose therapy

Treatment for multiple myeloma should not be given until the patient is symptomatic or at risk for the occurrence of complications of the disease. If the patient is younger than 70 years, the physician should seriously consider an autologous peripheral blood stem cell transplant. Most physicians initially administer vincristine/doxorubicin/dexamethasone (VAD) for 3 to 4 months and then collect the stem cells before exposure to alkylating agents. Following stem cell collection, one may proceed with high-dose chemotherapy and then infusion of the stem cells, or one can administer alkylating agents until a plateau is reached and delay transplantation until progressive disease occurs. There is no difference in overall survival between early and late transplantation, but the former avoids the cost and inconvenience of alkylating agent therapy. Double or tandem autologous stem cell transplants may produce better results, but the evidence is not strong. Almost all patients have a relapse after an autologous stem cell transplant, so efforts are being made to prolong the response with a2-interferon or dendritic cell therapy. Allogeneic bone marrow transplantation is feasible for only 5%-10% of patients, but the mortality is high and it is curative in only a small fraction of patients. Treatment with melphalan and prednisone results in an objective response in 50%-60% of patients. Combinations of alkylating agents produce a higher response rate, but there is no survival benefit. Thalidomide produces an objective response in about one third of patients with refractory disease. It currently is being studied in conjunction with dexamethasone for conventional initial therapy.