Background: The phase 3 ENDEAVOR trial demonstrated significantly improved PFS and OS with Kd56 vs Vd in RRMM patients (pts; Dimopoulos Lancet Oncol 2016 and 2017). We report updated data after additional follow-up. Methods: Hazard ratios (HRs) and 95% CIs were estimated using stratified or unstratified Cox proportional hazards models for primary and subgroup OS analyses, respectively. Results: 929 pts were randomized (Kd56, n = 464; Vd, n = 465). As of 19-Jul-17, median OS was 47.8 (Kd56) vs 38.8 (Vd) months (mos; HR, 0.76 [95% CI, 0.633–0.915]; median follow-up, 44.3 vs 43.7 mos). OS was longer with Kd56 vs Vd within age subgroups ( < 65 years [yrs]: median, 47.8 vs 42.2 mos; HR, 0.79 [95% CI, 0.598–1.031]; 65–74 yrs: median, 49.0 vs 36.2 mos; HR, 0.71 [95% CI, 0.520–0.958]; ≥75 yrs: median, 36.1 vs 23.9 mos; HR, 0.78 [95% CI, 0.506–1.199]). OS was longer with Kd56 vs Vd by prior lines of therapy (1 line: median, 51.3 vs 43.7 mos; HR, 0.77 [95% CI, 0.583–1.018]; 2–3 lines: median, 39.5 vs 28.4 mos; HR, 0.75 [95% CI, 0.589–0.959]) and prior bortezomib (btz) exposure (prior btz: median, 41.8 vs 32.7 mos; HR, 0.85 [95% CI, 0.669–1.082; no prior btz: median, not estimable [NE] vs 42.2 mos; HR, 0.66 [95% CI, 0.496–0.875]). OS was longer with Kd56 vs Vd for high-risk (median, 28.0 vs 22.7 mos; HR, 0.81 [95% CI, 0.580–1.136]) and standard-risk (median, NE vs 43.5 mos; HR, 0.79 [95% CI, 0.618–1.009]) cytogenetics pts. 457 (98.7%, Kd56) and 451 (98.9%, Vd) pts had an adverse event (AE); 379 (81.9%, Kd56) and 324 (71.1%, Vd) had a grade ≥3 AE. Exposure-adjusted pt incidences per 100 pt-yrs (95% CI) of AEs were 1352.07 (1233.62–1481.89) for Kd56 and 1754.86 (1600.15–1924.53) for Vd; for grade ≥3 AEs, these values were 162.31 (146.77–179.50) and 175.90 (157.75–196.13). The most common AEs in the Kd arm (≥ 30% of subjects) were anemia (43.6%), diarrhea (36.7%), pyrexia (32.6%), hypertension (32.4%), fatigue (32.2%) and dyspnea (32.2%). Conclusions: With median follow-up of ~44 mos, clinically meaningful OS improvements were observed with Kd56 vs Vd, including in all subgroups examined. The Kd56 safety profile was consistent with previous analyses. Clinical trial information: NCT01568866