The FDA granted accelerated approval to selinexor (Xpovio, 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 two lines of systemic therapy.
“The clinical profile and tolerability of oral [selinexor] provides physicians and patients with a new treatment alternative to traditional intravenous chemotherapy regimens,” noted John P. Leonard, MD, the Richard T. Silver Distinguished Professor of Hematology and Medical Oncology at Weill Cornell Medicine and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center, in New York City.
The approval is based on the results of the multicenter, single-arm phase 2b SADAL (Selinexor Against Diffuse Aggressive Lymphoma) study (ClinicalTrials.gov Identifier: NCT02227251), which evaluated 134 patients with relapsed or refractory DLBCL. The patients, who had been treated with a median of two prior systemic therapies (up to five), were administered a fixed 60-mg dose of selinexor on days 1 and 3 of each week in a four-week cycle. Patients with germinal center B-cell (GCB) and non-GCB subtypes of DLBCL were included. Efficacy was assessed using overall response rate (ORR) and duration of response, as assessed by an independent review committee using Lugano 2014 criteria.
The SADAL study met its primary end point of ORR, at 29% (95% CI, 22%-38%), including 13% for complete response (n=18) and 16% for partial response (n=21).
Key secondary end points included a median duration of response. Of the 39 patients who achieved a partial or complete response, 56% maintained a response at three months, 38% at six months and 15% at 12 months.
The most common treatment-related adverse events (AEs), cytopenias and gastrointestinal and constitutional symptoms, generally were reversible and managed with dose modifications and/or standard supportive care. The most common nonhematologic AEs were fatigue (63%), nausea (57%), decreased appetite (37%), and diarrhea (37%), and were mostly grade 1 and 2. Grade 3 and 4 laboratory abnormalities occurring in at least 15% of patients included thrombocytopenia, lymphopenia, neutropenia, anemia and hyponatremia. Grade 4 laboratory abnormalities occurring in at least 5% of patients were thrombocytopenia (18%), lymphopenia (5%) and neutropenia (9%).
The selinexor prescribing information includes warnings and precautions related to thrombocytopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infection, neurologic toxicity, and embryo-fetal toxicity.
For more information, view the full prescribing information for selinexor.
As part of the accelerated approval, the FDA has agreed that the XPORT-DLBCL-030 study could serve as the confirmatory trial for evaluating selinexor in DLBCL. This placebo-controlled trial will assess selinexor added to a standard backbone of rituximab-gemcitabine-dexamethasone-platinum in patients with one to three prior treatments for DLBCL. Karyopharm reported that it anticipates the XPORT-DLBCL-030 study will begin by the end of 2020.
—Clinical Oncology News Staff
Based on press releases from the FDA and Karyopharm.