Vogl DT, et al. - Selinexor, a first-in-class, oral, selective exportin 1 (XPO1) inhibitor, induces apoptosis in cancer cells through nuclear retention of tumor suppressor proteins and the glucocorticoid receptor, along with inhibition of translation of oncoprotein mRNAs. In this study, selinexor + dexamethasone had an overall response rate (ORR) of 21% in patients with multiple myeloma refractory to the most active available agents.

• In this phase II trial, researchers assessed selinexor 80 mg and dexamethasone 20 mg, both orally and twice weekly, in patients with myeloma refractory to bortezomib, carfilzomib, lenalidomide, and pomalidomide (quad-refractory disease), with a subset also refractory to an anti-CD38 antibody (penta-refractory disease).
• Overall response rate (ORR) was the primary end point.

• A total of 79 patients were examined, of those 48 had quad-refractory and 31 had penta-refractory myeloma.
• Data showed that patients had received a median of 7 prior regimens.
• An ORR of 21% was reported and it was similar for patients with quad-refractory (21%) and penta-refractory (20%) disease.
• The reported ORR was 35% (six of 17 patients) among patients with high-risk cytogenetics, including t(4;14), t(14;16), and del(17p).
• Five months was the median duration of response.
• At 12 months, 65% of responding patients were found alive.
• Thrombocytopenia (59%), anemia (28%), neutropenia (23%), hyponatremia (22%), leukopenia (15%), and fatigue (15%) were identified as most commonly reported grade ≥ 3 adverse events.
• In addition, occurrence of dose interruptions for adverse events was reported in 41 patients (52%), while dose reductions occurred in 29 patients (37%), and treatment discontinuation occurred in 14 patients (18%).