On December 18, 2020, the FDA approved selinexor (Xpovio; Karyopharm Therapeutics) in combination with bortezomib (Velcade) and dexamethasone for the treatment of adults with multiple myeloma after ≥1 previous therapies. The FDA granted this indication an orphan drug designation.
Selinexor was previously approved in combination with dexamethasone for adults with relapsed or refractory multiple myeloma who have received ≥4 previous therapies, and for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after ≥2 lines of systemic therapy.
The FDA approved the new indication based on data from the BOSTON clinical trial, a randomized, open-label, multicenter, active comparator–controlled study in patients with relapsed or refractory multiple myeloma who had received between 1 and 3 previous therapies. Patients were randomized in a 1:1 ratio to once-weekly selinexor orally, in combination with once-weekly bortezomib subcutaneously and low-dose dexamethasone twice-weekly (SVd) or to the standard twice-weekly bortezomib plus low-dose dexamethasone (Vd) regimen.
The main end point was progression-free survival (PFS). The estimated median PFS was 13.9 months (95% confidence interval [CI], 11.7-not estimable) in the SVd arm versus 9.5 months (95% CI, 7.6-10.8) in the Vd arm (estimated hazard ratio, 0.70; 95% CI, 0.53-0.93).
The most common (≥20%) adverse reactions reported with the SVd arm were nausea, fatigue, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract, and vomiting. Grade 3 or 4 laboratory abnormalities (≥10%) were thrombocytopenia, lymphopenia, hypophosphatemia, anemia hyponatremia, and neutropenia.