OBJECTIVES Motivated by the discussion whether the german AMNOG is applied to currently marketed drugs we compared first-line therapies for patients with multiple myeloma (MM).  METHODS A systematic literature search for randomized controlled trials (RCTs) was conducted and VMP (bortezomib (Velcade), melphalan and prednisone), MPT (melphalan, prednisone and thalidomide) and MP (melphalan and prednisone) were identified as therapies of interest. We extracted information on overall survival (OS), progression-free survival (PFS), response criteria (CR, VGPR, PR), and grade 3-4 AEs (any, hematological, non-hematological, DVT, PNP). Random-effects meta-analysis was used for direct and the Bucher method for adjusted indirect treatment comparison. RESULTS Seven RCTs with a total of 2,367 patients were included in our analyses, one RCT (n=682) comparing VMP vs. MP and six RCTs (n=1,685) comparing MPT vs. MP. Direct head-to-head comparison of VMP vs. MPT was lacking. For MPT vs. MP, data were extracted from a recently published meta-analysis of individual patient data if available. VMP was superior to MP regarding OS. Both VMP and MPT were superior to MP regarding PFS and response criteria, but had a higher risk of developing AEs. The indirect comparison of VMP vs. MPT via MP showed a statistically not significant advantage for VMP regarding survival outcomes. Significant benefits were observed for CR and development of any grade 3-4 AEs favouring VMP. CONCLUSIONS Analysis of both aggregated and individual patient data essentially lead to the same conclusions, i.e. VMP and MPT seem more effective than MP, VMP seems ahead of MPT regarding response criteria and adverse events. We found significant between-trials heterogeneity, however no consistent relationship of effect and study-level covariates (e.g. maintenance dosing) was apparent. Thus, we relied on the random effects approach to meta-analysis to cope with the unexplained trial-to-trial variability. Our results may best be confirmed by a head-to-head trial of VMP vs. MPT.