Virtually no treatment options are available for patients with multiple myeloma (MM) refractory to proteasome inhibitors, immunomodulatory agents and monoclonal antibodies (triple-class refractory MM). Now, responses to selinexor, a novel selective inhibitor of exportin 1 (which is involved in the nuclear export of tumour suppressor proteins and is overexpressed in MM), have been reported in this setting.

In the single-arm phase II STORM trial, 122 patients with MM who had previously received bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab and an alkylating agent were treated with selinexor plus low-dose dexamethasone. A total of 32 patients (26%) had a partial response (PR) or better, including 2 stringent complete responses, 6 very good PRs and 24 PRs; in total, 48 patients (39%) had a minimal response or better. Median progression-free survival and overall survival (OS) durations were 3.7 months and 8.6 months, respectively. The subgroup of patients with a PR or better and those with a minimal response or better both had median OS durations of 15.6 months.

The most common grade 3–4 adverse events (AEs) were thrombocytopenia (in 59% of patients), anaemia (44%), hyponatraemia (22%) and neutropenia (21%). A total of 12 patients died from AEs, which were considered treatment-related in a patient with pneumonia and another one with sepsis.

Analysis of samples from 35 patients led to the identification of a four-protein classifier with high predictive performance (area under the curve 0.86). A predictive accuracy of 83% was observed in a validation set with samples from 12 patients.

The activity of selinexor in various combinations is being investigated in several comparative trials involving patients with MM. The publication of these results will enable to determine whether or not selinexor should be incorporated in the routine management of patients with MM.