On June 22, 2020, selinexor received accelerated approval by the FDA (Food and Drug Administration) for management of relapsed/refractory DLBCL (diffuse large B-cell lymphoma).
The drug’s intended use is for adult individuals having relapsed/refractory DLBCL, not otherwise specified, including DLBCL emerging from follicular lymphoma, after receiving at least two lines of systemic therapy. A multicenter, single-arm, open-label clinical trial (SADAL) was conducted in patients having DLBCL who had previously been administered two to five systemic regimens. On days 1 and 3 of each week, patients received 60 mg of selinexor orally.
The primary outcome ascertained was based on ORR (overall response rate) and duration of response, as assessed via Lugano 2014 criteria by an independent review committee. In 134 patients, the ORR was found to be 29%, with complete response in 13%. Of the 39 patients attaining a partial or complete response, 38% had response durations of at least six months and 15% had a response duration of at least 12 months.
In patients with DLBCL, the most common noxious effects (incidence ?20%), excluding laboratory abnormalities, were found to be nausea, fatigue, diarrhea, decrease in weight and appetite, constipation, pyrexia, and vomiting. Grade 3-4 laboratory abnormalities witnessed in ?15% were lymphopenia, thrombocytopenia, neutropenia, hyponatremia, and anemia.
In 46% of patients, serious adverse reactions occurred, most often from an infection. The leading cause of dose modifications was thrombocytopenia. In 80% of participants, GI (gastrointestinal) toxicity developed, and in 61%, hyponatremia developed. In 25% of patients, central neurological adverse reactions occurred, including mental status changes and dizziness.
The selinexor dose for DLBCL patients is advocated to be 60 mg oral administration on days 1 and 3 of each week. The prescribing information yields precautions and warnings for neutropenia, thrombocytopenia, GI toxicity, serious infection, hyponatremia, embryo-fetal toxicity, and neurological toxicity.
This indication received FDA-accelerated approval under approval based on the response rate witnessed in the SADAL trial. Upon verification and characterization of clinical benefit in confirmatory clinical studies, continued approval for these indications may be contingent.
Source: US FDA
Original title: FDA approves selinexor for relapsed/refractory diffuse large B-cell lymphomaAuthors: