Treatment of multiple myeloma

Background and Objective. Multiple myeloma (MM) accounts for about 10% of a ll hematologic malignancies. The standard treatment with intermittent cours es of melphalan and prednisone (MP) was introduced more than 30 years ago a nd, since then there has been little improvement in event-free and overall survival (EFS & OS). The aim of this article is to review: 1) the role of i nitial chemotherapy (ChT), maintenance treatment with a-interferon and salv age ChT, 2) the results of high-dose therapy (HDT) followed by allogeneic o r autologous stem cell transplantation (allo-SCT and auto-SCT), and 3) the most important supportive measures. Evidence and Information Sources. The authors of this review have been acti vely working and contributing with original investigations on the treatment of MM during the last 15 years. In addition, the most relevant articles an d recent abstracts published in journals covered by the Science Citation In dex(R) and Medline(R) are also reviewed. State of the Art and Perspectives. The importance of avoiding ChT in asympt omatic patients (smoldering MM) is emphasized. The criteria and patterns of response are reviewed. MP is still the standard initial ChT with a respons e rate of 50-60% and an OS of 2-3 years. Combination ChT usually increases the response rate but does not significantly influence survival when compar ed with MP. Exposure to melphalan should be avoided in patients in whom HDT followed by auto-SCT is planned, in order to not preclude the stem cell co llection. The median response duration to initial ChT is 18 months. Interfe ron maintenance usually prolongs response duration but in most studies does not significantly influence survival (a large meta-analysis by the Myeloma Trialists' Collaborative Group in Oxford is being finished). In alkylating -resistant patients, the best rescue regimens are VBAD or VAD. In patients already resistant to VBAD or VAD and in those in whom these treatments are not feasible we recommend a conservative approach with alternate day predni sone and pulse cyclophosphamide. While HDT followed by autotransplantation is not recommended for patients with resistant relapse, patients with prima ry refractory disease seem to benefit from early myeloablative therapy. Alt hough results from large randomized trials are still pending in order to es tablish whether early HDT intensification followed by auto-SCT is superior to continuing standard ChT in responding patients, the favorable experience with autotransplantation of the French Myeloma intergroup supports this ap proach. However, although the complete response rate is higher with intensi ve therapy, the median duration of response Is relatively short (median, 16 to 36 months), with no survival plateau. There are several ongoing trials comparing conventional ChT with HDT/autoSCT in order to identify the patien ts who are likely to benefit from one or another approach. With allo-SCT th ere is a transplant-related mortality ranging from 30 to 50% and also a hig h relapse rate in patients achieving CR. However, 10 to 20% of patients und ergoing allo-SCT are long-term survivors (<5 years) with no evidence of dis ease acid, consequently, probably cured. The use of allogeneic peripheral b lood stem cells (PBSC) in order to speed the engraftment and also the use o f partially T-cell depleted PBSC which can decrease the incidence of graft- versus-host disease are promising approaches. In the setting of allo-SCT, d onor lymphocyte infusion is an encouraging strategy in order to treat or pr event relapses. Finally, important supportive measures such as the treatmen t of anemia with erythropoietin, the management of renal failure and the us e of bisphosphonates are reviewed. (C)1999, Ferrata Storti Foundation.