On June 22, the U.S. Food and Drug Administration (FDA) approved oral selinexor (Xpovio), a first-in-class, selective inhibitor of nuclear export compound, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified after at least two lines of systemic therapy. It was also approved for adult patients with DLBCL arising from follicular lymphoma.
John P. Leonard, MD
“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,” said 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.
“Single-agent, oral selinexor demonstrated a clinically meaningful overall response rate of 29%, including a complete response rate of 13%, in the pivotal SADAL study across several disease subtypes. Importantly, some patient responses were durable, with 38% of responding patients maintaining a response at 6 months. The clinical profile and tolerability of oral selinexor provides physicians and patients with a new treatment alternative to traditional intravenous chemotherapy regimens,” he said.
The accelerated FDA approval of selinexor is based on the results from the multicenter, single-arm phase IIb SADAL study, which evaluated 134 patients with relapsed or refractory DLBCL who had been treated with a median of 2 prior systemic therapies (range = 1–5). Patients were administered a fixed 60-mg dose of selinexor given orally twice weekly for a 4-week cycle. Patients with germinal center B-cell or non–germinal center B-cell subtypes of DLBCL were included in enrollment.
The SADAL study met its primary endpoint, with an overall response rate of 29%, including 18 patients (13%) who showed a complete response and 21 (16%) who had partial responses.
Key secondary endpoints included a median duration of response in the responding patients; 56% maintained a response at 3 months, 38% at 6 months, and 15% at 12 months.
All 134 patients were included in the safety analyses. The most common treatment-related adverse events were cytopenias along with gastrointestinal and constitutional symptoms and were generally reversible and managed with dose modifications and/or standard supportive care. The most common nonhematologic adverse events were fatigue (63%), nausea (57%), decreased appetite (37%), and diarrhea (37%), and were mostly grade 1 and 2 events.
Grade 3 and 4 laboratory abnormalities in ≥ 15% of patients included thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Grade 4 laboratory abnormalities in ≥ 5% of patients were thrombocytopenia (18%), lymphopenia (5%), and neutropenia (9%).
The recommended selinexor dosage for patients with DLBCL is 60 mg taken orally on days 1 and 3 of each week with antiemetic prophylaxis.
As part of the FDA accelerated approval, the FDA has agreed that the XPORT-DLBCL-030 study could serve as the confirmatory trial for evaluating selinexor in DLBCL. This trial will assess the effect of selinexor or placebo added to a standard backbone immunochemotherapy of rituximab, gemcitabine, dexamethasone, and platinum in patients with one to three prior treatments for DLBCL. The XPORT-DLBCL-030 study is anticipated to begin by the end of 2020.