OBJECTIVES: Relapsed / refractory multiple myeloma (rrMM) remains challenging to treat effectively. Results of two major phase III randomized controlled trials (RCTs), ASPIRE for carfilzomib and ELOQUENT-2 for elotuzumab, both in combination with lenalidomide and dexamethasone (CLD and ELD respectively) in rrMM were compared to placebo plus lenalidomide and dexamethasone (LD). We performed an indirect treatment comparison (ITC) to compare CLD versus ELD.  METHODS: We evaluated clinical and safety endpoints from both trials. We derived risk ratios (RRs) and mean differences (MD) for dichotomous and continuous outcome respectively using RevMan 5.0. We further computed the ITC RRs and MDs using the Canadian Agency for Drugs and Technologies in Health (CADTH) ITC application which employs Bucher et al. (1997) method. ITC was conducted to compare CLD versus ELD for median progression-free survival (PFS) in months, median duration of response (DoR) in months and overall response rate (ORR). RESULTS: Complete response (CR) and very good partial response (VGPR) were 8 and 2.5 times higher in CLD than ELD respectively. Overall survival (OS) was not reached in both the trials, but mortality was higher in CLD as compared to ELD. All / any grade adverse events AEs were lower in CLD than ELD while grade 3 or higher AEs were similar for both combinations. The PFS (MD=4.20; 95% CI: -2.09, 10.49; p=0.03) and DoR (MD=3.29; 95% CI: -5.19, 11.78; p=0.02) were significantly higher in CLD as compared to ELD. ORR (RR=1.09; 95% CI: 0.97, 1.23; p=0.73) was not significantly different between the two treatments. CONCLUSIONS: While both combinations significantly perform better than LD, our findings suggest CLD may perform better than ELD however caution should be exercised in interpreting these results. More time and trial data are needed to confirm this initial observation as well as determine any differences in overall survival.