Despite a high rate of grade 3 to 4 adverse events (AEs), selinexor showed promising clinical activity among heavily pretreated patients with multiple myeloma, according to a study published in the Journal of Clinical Oncology.1

Patients with quad- or penta-refractory myeloma have limited treatment options. Selinexor, an orally administered selective inhibitor of exportin 1 (XPO1), previously showed anti-myeloma activity in a phase 1 trial.

Of 79 patients enrolled to this phase 2 trial, 48 had quad-refractory (to bortezomib, carfilzomib, lenalidomide, and pomalidomide) and 31 had penta-refractory (to the aforementioned 4 and an anti-CD38 antibody) disease. All patients received selinexor 80 mg and dexamethasone 20 mg twice weekly.

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The overall median age was 63 years, the median number of years since diagnosis was 4 (range, 3-17), and 56% of the 39 patients with cytogenetic assessments had standard-risk cytogenetics.

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Seventy-eight patients were included in the efficacy analysis. The overall response rate was 21% (21% among patients with quad-refractory disease and 20% among patients with penta-refractory disease). Four patients had a very good partial response, 12 patients had a partial response, 10 patients had a minimal response, and 27 had stable disease.

Among the 17 patients with high-risk cytogenetics, the overall response rate was 35%.

The median progression-free survival was 2.3 months; median overall survival was 9.3 months.

The rate of grade 3 to 4 AEs was, however, high: 59% of patients had grade 3 or 4 thrombocytopenia, 23% of patients had grade 3 or 4 neutropenia, and 28% of patients had grade 3 or 4 anemia. Fourteen patients discontinued treatment.

The authors concluded that “selinexor is an oral agent with a novel mechanism of action and evidence of antimyeloma efficacy. In combination with low-dose dexamethasone, selinexor is an effective therapy for patients with refractory multiple myeloma for whom available treatments have been exhausted.”


  1. Vogl DT, Dingli D, Cornell RF, et al. Selective inhibition of nuclear export with oral selinexor for treatment of relapsed or refractory multiple myeloma. J Clin Oncol. 2018 Jan 30. doi: 10.1200/JCO.2017.75.5207 [Epub ahead of print]