Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials.

PURPOSE: To compare combination chemotherapy (CCT) versus melphalan plus prednisone (MP) as treatment for multiple myeloma. PATIENTS AND METHODS: In a collaborative worldwide overview of randomized trials of CCT versus MP, individual patient data on 4,930 patients from 20 trials were analyzed, with the addition of published data on a further 1,703 patients from seven trials. The main outcome measure was mortality, with response and recurrence rates being subsidiary end points. RESULTS: Taking all of the trials together, response rates were significantly higher with CCT than with MP (60.0% v 53.2%; P < .00001, two-tailed). There was no evidence of any difference in mortality between CCT and MP, with a nonsignificant 1.5% reduction in death rate in favor of CCT (P = .6, two-tailed). There is heterogeneity of design between the trials, but subgroup analyses by type of CCT or by dose-intensities of CCT, of melphalan, or of prednisone did not identify any particular forms of therapy that were either clearly beneficial or clearly adverse. Similarly, analysis of the presentation features of the patients did not find any categories in which CCT differed significantly from MP in its effects on mortality; in particular, there was no evidence that poor-risk patients benefited more from CCT. CONCLUSION: This overview found no difference, either overall or within any subgroup, in mortality between CCT and MP. In terms of survival, these therapeutic options, as tested in the trials considered, are approximately equivalent.