Combination chemotherapy versus melphalan plus prednisone as treatment formultiple myeloma: An overview of 6,633 patients from 27 randomized trials

Purpose: To compare combination chemotherapy (CCT) versus melphalan plus pr ednisone (MP) as treatment for multiple myeloma. Patients and Methods: In a collaborative worldwide overview of randomized t rials of CCT versus MP, individual patient data on 4,930 patients from 20 t rials were analyzed, with the addition of published data on a further 1,703 patients from seven trials. The main outcome measure was mortality, with r esponse and recurrence rates being subsidiary end points. Results: Taking all of the trials together, response rates were significant ly higher with CCT than with MP (60.0% v 53.2%; P < .00001, two-tailed). Th ere 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 eith er clearly beneficial or clearly adverse. Similarly, analysis of the presen tation features of the patients did not find any categories in which CCT di ffered significantly from MP in its effects on mortality; in particular, th ere 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 the rapeutic options, as tested in the trials considered, are approximately equ ivalent. (C) 1998 by American Society of Clinical Oncology.