Triple-class-refractory multiple myeloma (MM) describes MM refractory to proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies. In the Phase IIb STORM study (NCT02336815), oral selinexor plus low-dose dexamethasone (Sel-dex) demonstrated a 26.2% overall response rate in triple-class-refractory MM. Here, we compare overall survival (OS) of 122 patients with triple-class-refractory MM who received Sel-dex in STORM Part 2 with that of 64 similar patients treated with other available therapies in a Flatiron Health Analytic Database (FHAD) cohort. OS from the date that the patients MM became triple-class-refractory was longer in STORM versus FHAD, with an unadjusted hazard ratio (HR) of 0.43 (P =  .0002; adjusted HR 0.35 [P  =  .011]). In a subset analysis of highly resistant patients receiving further therapies after their MM first became at least triple-class-refractory (i.e., who received Sel-dex in STORM, n = 64, and non-Sel-dex in FHAD, n = 36), the OS was significantly longer in STORM with an unadjusted HR of 0.52 (P = .0331; adjusted HR 0.33 [P = .041]). Within the limits of this analysis, the OS of patients with at least triple-class-refractory MM was significantly better with Sel-dex versus available therapies, suggesting that Sel-dex may be associated with a meaningful OS benefit in these patients.