Background: Addition of daratumumab, a CD38 monoclonal antibody, to standard of care (SOC) myeloma induction regimens resulted in deeper responses. Phase 3 trials comparing daratumumab + SOC vs SOC consistently favored the daratumumab combinations. The objective of this analysis is to test the hypothesis that high-risk patients benefit from the addition of daratumumab to SOC induction regimens. Methods: We identified four phase 3 clinical trials (RCT) that randomized newly diagnosed myeloma patients to receive daratumumab +SOC vs. SOC. The GRIFFIN trial did not have PFS events and was excluded. A meta-analysis of 3 RCTs with updated data from ASH 2019 (ALCYONE, MAIA, CASSIOPEIA) was performed using the fixed (Mantel-Haenszel) model to calculate the impact of daratumumab + SOC versus SOC. The consistency of results (effect sizes) among studies was investigated by means of two heterogeneity tests, the χ 2-based Cochran's Q test, and the I² Statistic. We considered that heterogeneity was present when the P value of the Cochran's Q test was < 0.1 and I² statistic was > 50%. Results: The pooled hazard ratios (HR) for standard risk patients for PFS was HR 0.589 (95% CI 0.502-0.691; P< 0.001) in favor of daratumumab. Q-statistic for PFS (P= 3.462; df= 2; I² = 42.23) suggests homogeneity across studies. The pooled hazard ratios (HR) for high risk patients for PFS was HR 0.799 (95% CI 0.609-1.047; P= 0.104) in favor of daratumumab. Q-statistic for PFS (P= 1.306; df= 2; I² = 0.00) suggests homogeneity across studies. Conclusions: Our meta-analysis demonstrates that addition of daratumumab to SOC myeloma induction regimens prevented progression in both standard and high-risk patients, though the impact was more pronounced in the standard-risk patients. This benefit seems to improve with longer follow up, as seen both in ALCYONE (Mateos et al ASH 2019) and MAIA trial (Bahlis et al ASH 2019). Focused accrual of high-risk patients in larger daratumumab induction trials and longer follow up of the existing trials are further needed.