Selinexor in combination with low dose dexamethasone is active in heavily pretreated patients with refractory multiple myeloma, including those with disease refractory to anti-CD38 monoclonal antibodies and those with high-risk cytogenetic abnormalities, a study presented at the American Society of Hematology (ASH) 58th Annual Meeting and Exposition has shown.1

Nearly all patients with multiple myeloma are expected to become “quad refractory” to immunomodulatory agents like lenalidomide and pomalidomide and to proteasome inhibitors like bortezomib and carfilzomib, and eventually “penta refractory” to anti-CD38 monoclonal antibodies. In phase 1 clinical trials, selinexor, an oral selective XPO1 inhibitor, plus low dose dexamethasone demonstrated potent activity in patients with multiple myeloma.

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Therefore, researchers sought to evaluate selinexor combined with low dose dexamethasone in patients with multiple myeloma refractory to bortezomib, carfilzomib, lenalidomide, and pomalidomide, with a subset of patients also refractory to daratumumab or isatuximab. For the multicenter, open-label, single-arm, phase 2b STORM study ( Identifier: NCT02336815), investigators enrolled 79 patients, of which 48 and 21 were “quad refractory” and “penta refractory,” respectively.

All participants received oral selinexor 80 mg twice weekly for 6 or 8 doses and dexamethasone 20 mg twice weekly per each 28-day cycle. Patients all received 5-HT3 antagonists for prevention of nausea and vomiting.

Results showed that 21% achieved an objective response rate, including 5% who achieved very good partial responses. The overall response rate for “quad refractory” and “penta refractory” myeloma was 21% and 20%, respectively.

In addition, the clinical benefit rates were 32% overall, 29% in “quad refractory” patients, and 37% in “penta refractory” patients. Median overall survival was not reached for responders and was 5.7 months for non-responders. Median progression-free survival for all patients was 2.1 months.

With respect to cytogenetic abnormalities, 33% of the 18 patients with high-risk FISH abnormalities achieved an overall response, including 1 very good partial response and 5 partial responses.

The most common grade 3 to 4 treatment-related adverse events were thrombocytopenia (58%), anemia (25%), neutropenia (21%), asymptomatic hyponatremia (20%), and fatigue (14%). Seventeen percent of patients discontinued selinexor therapy due to adverse events.

In this population of patients with multiple myeloma who have exhausted most of the currently available treatment options, selinexor represents a novel treatment strategy for heavily refractory multiple myeloma. Further evaluation of selinexor plus dexamethasone in “penta refractory” patients is planned.


1. Vogl DT, Dingli D, Cornell RF, et al. Selinexor and low dose dexamethasone (Sd) in patients with lenalidomide, pomalidomide, bortezomib, carfilzomib and anti-CD38 Ab refractory multiple myeloma (MM): STORM study. Paper presented at: American Society of Hematology (ASH) 58th Annual Meeting and Exposition; December 3-6, 2016; San Diego, CA.