Background: Treatment for multiple myeloma (MM) in the US has undergone significant advances, with several new therapies recently FDA approved for relapse/refractory MM (RRMM), including carfilzomib+lenalidomide+dex (KRd), carfilzomib+dex (Kd), daratumumab+lenalidomide+dex (DRd), daratumumab+bortezomib+dex (DVd), ixaxomib+lenalidomide+dex (IRd), and elotuzumab+lenalidomide+dex (ERd). These new therapies have shown improvements in clinical outcomes in randomized controlled trials (RCTs). However, with few head-to-head RCTs, there is little comparative evidence to determine the most effective treatment for specific patients. A systematic literature review (SLR) and network meta-analysis (NMA) was conducted to determine the comparative efficacy (progression free survival (PFS)) of MM therapies for treating first relapse. Methods: The SLR searched MEDLINE, Embase, and the Cochrane Library for RCTs investigating the efficacy of treatments for RRMM (to August 2016). NMA was conducted on the PFS hazard ratios (HR), where available in RCTs for patients with one prior line of treatment, using Bayesian fixed effects mixed treatment comparisons. Results: Data formed two evidence networks. Network 1: RCTs with Rd; Network 2: RCTs with Vd. Analyses found DRd and DVd had the highest probability of being the best treatment (0.96 and 0.89, respectively). Compared to other MM therapies, DRd and DVd had the lowest risk of progression or death (PFS HR <1.0) (Table 1). For example, compared to KRd, DRd had a 41% (PFS HR 0.59) reduced risk of progression or death. Conclusions: This analysis provides comparative evidence among treatments where head-to-head RCTs have not been conducted. For treating first relapse, compared to other MM treatments, this analysis found that DRd and DVd had the highest probability of providing the longest progression free survival.