The FDA has granted accelerated approval to selinexor for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after 2 previous lines of therapy. Selinexor is an oral selective inhibitor of nuclear export (SINE) compound which inhibits the nuclear export protein exportin 1 (XPO1).
Approval was supported by results from the SADAL trial, a multicenter, single-arm, open-label trial in patients with DLBCL who had received 2 to 5 previous therapies. The trial enrolled 134 patients who received selinexor 60 mg weekly. Key endpoints were overall response rate (ORR) and response duration.
The ORR for the treatment was 29%, with 13% of patients achieving a complete response. Of 39 patients who achieved at least a partial response, 38% maintained a response duration of at least 6 months and 15% had durations of at least 12 months.
Selinexor is approved for a dosage of 60 mg taken orally on days 1 and 3 of each week with antiemetic prophylaxis. The most common adverse events (AEs), occurring in more than 20% of patients with DLBCL, were fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities, occurring in more than 15% of patients, were thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Serious AEs occurred in 46% of patients, most often from infection.
The drug was previously approved at 80 mg in combination with dexamethasone for adults with relapsed/refractory multiple myeloma who received at least four prior therapies and are refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.