Isatuximab–pomalidomide–dexamethasone vs. pomalidomide–dexamethasone in patients with relapsed and refractory multiple myeloma: final overall survival analysis

Abstract The primary and pre-specified updated analyses of ICARIA-MM (NCT02990338) demonstrated improved progression-free survival and a benefit in overall survival (OS) was reported with the addition of isatuximab, an anti-CD38 monoclonal antibody, to pomalidomide–dexamethasone (Pd) in patients with relapsed/refractory multiple myeloma. Here, we report the final OS analysis. This multicenter, randomized, open-label, phase 3 study included patients who had received and failed ≥2 previous lines of therapy, including lenalidomide and a proteasome inhibitor. Between January 10, 2017, and February 2, 2018, 307 patients were randomized (1:1) to isatuximab–pomalidomide–dexamethasone (Isa-Pd; n = 154) or Pd ( n = 153), stratified based on age (<75 vs. ≥75 years) and number of previous lines of therapy (2–3 vs. >3). At data cutoff for the final OS analysis after 220 OS events (January 27, 2022), median follow-up duration was 52.4 months. Median OS (95% confidence interval) was 24.6 months (20.3–31.3 months) with Isa-Pd and 17.7 months (14.4–26.2 months) with Pd (hazard ratio = 0.78; 95% CI, 0.59–1.02; 1-sided P = 0.0319). This analysis showed a clinically meaningful, continued OS benefit with Isa-Pd, which is well tolerated after follow-up of approximately 52 months in patients with relapsed/refractory multiple myeloma. Trial registration: ClinicalTrials.gov, number NCT02990338