FDA Grants Accelerated Approval to Selinexor

The Food and Drug Administration (FDA) has granted accelerated approval to selinexor (XPOVIO, Karyopharm Therapeutics) in combination with dexamethasone for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.

Efficacy was evaluated in 122 patients enrolled in Part 2 of STORM (KCP-330-012; NCT02336815), a multicenter, single-arm, open-label study of patients with RRMM who had previously received three or more anti-myeloma treatment regimens including an alkylating agent, glucocorticoids, bortezomib, carfilzomib, lenalidomide, pomalidomide, and an anti-CD38 monoclonal antibody. In addition, the disease was refractory to glucocorticoids, a proteasome inhibitor, an immunomodulatory agent, an anti-CD38 monoclonal antibody, and to the last line of therapy. These patients were treated with selinexor (80 mg) in combination with dexamethasone (20 mg) on days 1 and 3 of every week.

The approval was based on efficacy and safety in a prespecified subgroup analysis of 83 patients whose disease was refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab. The overall response rate was 25.3% (95% CI: 16.4, 36), with 1 stringent complete responses (CR), no CR, 4 very good partial responses and 16 partial responses. The median time to first response was 4 weeks (range: 1 to 10 weeks). The median response duration was 3.8 months (95% CI: 2.3, not estimable). The efficacy evaluation was supported by additional information from an ongoing, randomized trial in patients with multiple myeloma.

Common adverse reactions reported in at least 20% of patients include thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

The recommended selinexor dose is 80 mg in combination with dexamethasone taken orally on days 1 and 3 of each week.

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