FDA approves Xpovio for relapsed or refractory DLBCL
The FDA granted accelerated approval to selinexor for treatment of adults with relapsed or refractory diffuse large B-cell lymphoma who received at least two prior lines of systemic therapy.
Selinexor (Xpovio, Karyopharm Therapeutics) is the only single-agent oral therapy approved for treatment of patients with relapsed or refractory DLBCL.
Selinexor is a first-in-class, oral selective inhibitor of nuclear export compound. The drug binds with and inhibits the nuclear export protein XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus.
“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,” John P. Leonard, MD, Richard T. Silver distinguished professor of hematology and medical oncology at Weill Cornell Medicine and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center, said in a Karyopharm-issued press release. “The clinical profile and tolerability of oral Xpovio provides physicians and patients with a new treatment alternative to traditional IV chemotherapy regimens.”
The FDA previously approved selinexor for treatment of adults with relapsed or refractory multiple myeloma who received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents and an anti-CD38 monoclonal antibody.
The agency based the new indication on results of the multicenter, single-arm, phase 2b SADAL study, which included 134 patients with relapsed or refractory DLBCL who received a median two (range, 1-5) prior systemic therapies.
Patients received selinexor dosed at 60 mg twice weekly for a 4-week cycle.
The study met its primary endpoint of overall response rate. Researchers reported a 29% ORR, including 18 (13%) complete responses and 21 (16%) partial responses.
Duration of response served as a key secondary endpoint. More than half (56%) of patients who responded to therapy maintained their response for 3 months, 38% maintained their response for 6 months, and 15% remained in response at 12 months.
The most common treatment-related adverse events included cytopenias, as well as gastrointestinal and constitutional symptoms. Most of these events were reversible and managed with standard supportive care and/or dose modifications.
The most common nonhematologic adverse events included fatigue (63%), nausea (57%), decreased appetite (37%) and diarrhea (37%). Most of these events were grade 1 or grade 2.
Grade 3 and grade 4 laboratory abnormalities that occurred among at least 15% of patients included thrombocytopenia, lymphopenia, neutropenia, anemia and hyponatremia. Grade 4 laboratory abnormalities included thrombocytopenia (18%), lymphopenia (5%) and neutropenia (9%).
“The accelerated approval of oral Xpovio [for] patients with relapsed or refractory DLBCL is a significant milestone for the patients and families who currently have limited treatment options available,” Sharon Shacham, PhD, MBA, founder, president and chief scientific officer of Karyopharm, said in the press release. “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.”