Chari A, Vogl DT, Gavriatopoulou M, et al. – In this study, researchers investigated the efficacy of oral selinexor plus dexamethasone for the treatment of triple-class refractory multiple myeloma. A total of 122 and 123 patients in the United States and Europe were included in the modified intention-to-treat population (primary analysis) and the safety population, respectively. Eligible patients included those with myeloma who were previously exposed to bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent and had disease refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab (triple-class refractory). Patients were randomized to twice weekly oral selinexor 80 mg plus dexamethasone 20 mg. Overall response—defined as partial response or better, with response assessed by an independent review committee—was the primary endpoint; the second endpoint included clinical benefit, defined as a minimal response or better. In 26% of patients, partial response or better was noted, including two stringent complete responses, and 39% of patients had a minimal response or better. The median duration of response, median progression-free survival, and median overall survival was 4.4 months, 3.7 months, and 8.6 months, respectively. Fatigue, nausea, and decreased appetite were prevalent, and were typically grade 1 or 2 events. In 73% of the patients, the occurrence of thrombocytopenia was noted. In six patients, thrombocytopenia resulted in bleeding events of grade 3 or higher. Thus, in patients with myeloma refractory to currently available therapies, selinexor in combination with dexamethasone led to objective treatment responses.