On June 22, 2020, the FDA granted accelerated approval to the nuclear export inhibitor selinexor (Xpovio) 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 approval is based on the results of the multicenter, single-arm phase IIb SADAL (Selinexor Against Diffuse Aggressive Lymphoma) study, which assessed 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 4-week cycle. Patients with germinal center B-cell (GCB) and non-GCB subtypes of DLBCL were included. Efficacy was evaluated using overall response rate (ORR) and duration of response, as measured by an independent review committee using Lugano 2014 criteria. Key secondary endpoints included median duration of response. The SADAL study met its primary endpoint of ORR at 29% (95% CI, 22%-38%), including 13% for complete response (n = 18) and 16% for partial response (n = 21). Of the 39 patients who achieved a partial or complete response, 56% maintained a response at 3 months, 38% at 6 months, and 15% at 12 months. 

In a recent press release, John P. Leonard, MD, the Richard T. Silver Distinguished Professor of Hematology and Medical Oncology at Weill Cornell Medicine and an oncologist at New York-Presbyterian/Weill Cornell Medical Center in New York City, stated, “For the significant number of patients with relapsed or refractory DLBCL, there is an important need for new therapies for this particularly vulnerable patient population. Unfortunately, despite often multiple types of chemotherapy and targeted-drug combination therapy, many patients have disease which continues to progress. The clinical profile and tolerability of oral [selinexor] provides physicians and patients with a new treatment alternative to traditional intravenous chemotherapy regimens.”                                                                                                                                           

The most common treatment-related adverse events (AEs) were cytopenias and gastrointestinal and constitutional symptoms, which were usually were reversible and managed with dose adjustments and/or standard supportive care. The most common nonhematologic AEs were fatigue (63%), nausea (57%), decreased appetite (37%), and diarrhea (37%), and they 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%). Full prescribing information may  be found at XPOVIA.

As part of the accelerated approval, the FDA established that the XPORT-DLBCL-030 study could serve as the confirmatory trial for assessing selinexor in DLBCL. This placebo-controlled study will assess selinexor added to a standard regimen of rituximab-gemcitabine-dexamethasone-platinum in patients with one to three prior treatments for DLBCL. The manufacturer expects that the XPORT-DLBCL-030 study will begin by the end of 2020.

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