The Food and Drug Administration (FDA) has granted accelerated approval of Xpovio® (selinexor; Karyopharm) for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy.
The approval was based on data from the multicenter, single-arm, open-label phase 2b SADAL study that evaluated selinexor in 134 adult patients with relapsed or refractory DLBCL after 2 to 5 systemic regimens, including those with germinal center B-cell (GCB) or non-GCB subtypes of DLBCL. Patients received selinexor 60mg orally on Days 1 and 3 of each week for a 4-week cycle. Efficacy was measured by overall response rate (ORR) and duration of response (DoR).
Results showed an ORR of 29% (n=39) with selinexor, of which 13% of patients (n=18) had a complete response and 16% (n=21) had partial response. Among the 39 responding patients, 56% (n=22) maintained a response at 3 months, 38% (n=15) maintained a response at 6 months and 15% (n=6) maintained a response at 12 months.
With regard to safety, the most common treatment-related adverse events were cytopenias and gastrointestinal/constitutional symptoms. The most common nonhematologic adverse events were mostly Grade 1 and 2 events that included fatigue (63%), nausea (57%), decreased appetite (37%), and diarrhea (37%). Grade 3 and 4 laboratory abnormalities (≥15%) included thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Grade 4 laboratory abnormalities (≥5%) were thrombocytopenia (18%), lymphopenia (5%), and neutropenia (9%).
Continued approval for Xpovio in the treatment of DLBCL may be contingent upon verification of clinical benefit in confirmatory trials. According to Karyopharm, the phase 2/3 XPORT-DLBCL-030 study is expected to serve as the confirmatory trial. The study is anticipated to begin at the end of 2020.
“This approval marks the first for an oral agent for patients with previously treated DLBCL and the first approval of any single drug for this highly aggressive type of lymphoma,” said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm.
Xpovio, a nuclear export inhibitor, is already indicated in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies and whose disease is resistant to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody.
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