FDA Approves Selinexor for Relapsed/Refractory Myeloma

The FDA approved selinexor (Xpovio) plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma, who had at least 4 prior therapies, and are refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody.

Recommended dosing for selinexor is 80 mg plus 20 mg of dexamethasone given orally on days 1 and 3 of each week.

The approval came after an extended review period by the FDA, pushing back the action date to July 6, 2019. In February, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted against accelerated approval of the drug, stating that the agency hold off on a decision until results from the phase III BOSTON trial become available.

The 2-arm randomized, active comparator-controlled, open-label, multicenter phase III BOSTON trial compared both the efficacy and health-related quality of life among patients given selinexor plus bortezomib (Velcade) plus low-dose dexamethasone — a regimen referred to as SVdX – versus bortezomib plus low-dose dexamethasone (Vd).

In addition, the multi-center, single-arm, open-label STORM trial analyzed selinexor plus dexamethasone. STORM part 2 included 122 patients with relapsed/refractory disease who previously had 3 or more treatments including: an alkylating agent, glucocorticoids, bortezomib, carfilzomib (Kyprolis), lenalidomide (Revlimid), pomalidomide (Pomalyst), and an anti-CD38 monoclonal antibody. Trial participants also had myeloma that was refractory to glucocorticoids, a proteasome inhibitor, an immunomodulatory agent, an anti-CD38 monoclonal antibody, and to the last line of therapy that they had.

The approval was based on results from the 83 patients on the STORM trial who were refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab (Darzalex). This group had a 25.4% overall response rate, 1% stringent complete response rate, 5% very good partial response, and 19% partial response rate.

Median time to response was 4 weeks (range, 1-10), with average duration of response being 3.8 months.

The most common adverse events (AEs) that selinexor plus dexamethasone caused, which occurred in 20% or more of patients were: thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

A total of 28.5% of patients discontinued treatment due to treatment-related AEs, and the majority (88.6%) needed at least 1 dose modification as a result of AEs. Twenty-three patients died within 30 days of study treatment; 10 were a result of AEs, and 13 were from disease progression.