FDA Grants Selinexor Fast-Track Status

The U.S. Food and Drug Administration granted fast-track status to selinexor, an XPO1 inhibitor, for patients with heavily pretreated multiple myeloma (MM) who have become refractory to immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and investigational anti-CD38 antibodies. The designation is based on the results of the phase II STORM study, which evaluated selinexor plus low-dose dexamethasone in 78 patients with MM.

Patients had received a median of seven prior therapies and were refractory to bortezomib, carfilzomib, lenalidomide, and pomalidomide (“quad-refractory;” n=48); a subset of 30 patients was refractory to an investigational anti-CD38 antibody (either daratumumab or isatuximab; “penta-refractory”).

Patients were treated with selinexor 80 mg twice weekly for six or eight doses per 28-day cycle and dexamethasone 20 mg twice weekly. Most patients who were refractory to IMiDs and PIs received eight doses of selinexor per cycle (65%) and most patients who were refractory to IMiDs, PIs, and anti-CD38 antibodies received six doses of selinexor per cycle (83%).

The overall response rate (including partial responses [PR] and very-good PR) was 21 percent for all patients – 21 percent in the quad-refractory group and 20 percent in the penta-refractory group.

The median progression-free survival for all patients was 2.1 months, and the median OS was 9.3 months (ranges not reported). Among the patients who responded to treatment, the median OS was not reached at the time of data reporting (>11 months), compared with 5.7 months for non-responders.

The most common treatment-related hematologic adverse events (AEs) included thrombocytopenia (72%), anemia (48%), and neutropenia (29%), while the most common non-hematologic AEs included nausea (72%), fatigue (62%), anorexia (49%), vomiting (43%), asymptomatic hyponatremia (42%), diarrhea (42%), and weight loss (33%). There was one case of febrile neutropenia (1%) and one case of clinically significant bleeding related to thrombocytopenia (1%).

Sources: Karyopharm Therapeutics press release, April 10, 2018; 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. Abstract #491. Presented at the ASH Annual Meeting and Exhibition, December 4, 2016; San Diego.

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