Richardson PG, Kumar SK, Masszi T, et al. - Given ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) has been shown to confer a statistically significant improvement in progression-free survival compared with placebo-Rd in patients with relapsed or refractory multiple myeloma in the double-blind, placebo-controlled, phase III TOURMALINE-MM1 study, thus, researchers herein present the final analyses for overall survival (OS). Patients were randomized to ixazomib-Rd (n = 360) or placebo-Rd (n = 362), stratified by number of previous therapies (1 v 2 or 3), prior proteasome inhibitor (PI) exposure (yes v no), and International Staging System disease stage (I or II v III). In the both arms, the longest median OS values were documented in phase III studies of Rd-based triplets in relapsed or refractory multiple myeloma at the time of this analysis; progression-free survival advantage conferred by ixazomib-Rd vs placebo-Rd failed to translate into a statistically significant OS advantage on intent-to-treat analysis. Subgroups with adverse prognostic factors experienced a greater OS benefit. Imbalances in subsequent therapies received, particularly PIs and daratumumab, confounded OS interpretation.