Melphalan/prednisone versus drug combinations for plasma cell myeloma

Reports of 13 prospective, randomized clinical trials comparing standard treatment with melphalan and prednisone (MP) versus various drug combinations in the treatment of myeloma patients are presented. These studies reveal that patients with Durie-Salmon Stage III disease respond significantly more frequently to MP and drug combinations than those with Stage I and II. Drug combinations may be more effective in inducing objective responses. The response rates were significantly better for the drug combinations in 3 of the 13 comparisons. There was little evidence that either form of treatment was superior in prolonging survival, for in one study the patients treated with a drug combination lived significantly longer than those treated with MP, while in another the reverse was true, and there was no difference in the survival of the two groups in the remaining 11 studies. In the Vth MRC myelomatosis trial, patients treated with a combination of adriamycin, carmustine, cyclophosphamide and melphalan are living significantly longer than those treated with melphalan alone, and this survival advantage persists after correction for the most important prognostic factor, beta 2 microglobulin. Attempts to increase the intensity of treatment by using syngeneic, allogeneic or autologous marrow transplantation to rescue patients following otherwise lethal chemoradiotherapeutic treatments, have not yet demonstrated conclusively that the myeloma clone can be eliminated by this form of treatment.