Selinexor Approved Under Accelerated Pathway to Treat DLBCL

The FDA granted accelerated approval to selinexor (Xpovio, Karyopharm Therapeutics) for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The oral treatment is to be used after at least 2 lines of systemic therapy.

The approval was based on response rate as determined in the SADAL trial, a multicenter, single-arm, open-label trial in patients with DLBCL who had received 2 to 5 systemic regimens.

“The accelerated approval of oral Xpovio in patients with relapsed or refractory DLBCL is a significant milestone for the patients and families who currently have limited treatment options available for their disease,” Sharon Shacham, PhD, MBA, founder, president, and chief scientific officer of Karyopharm, said in a statement. “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.”

The phase 2b study evaluated 134 patients who were given 60 mg of selinexor orally twice weekly for a 4-week cycle. The study had an overall response rate (ORR) of 29%, including 18 (13%) complete responses, and 21 (16%) partial responses. Of the 39 patients who achieved a partial or complete response, 38% had a response duration of at least 6 months and 15% had a response duration of at least 12 months. ORR and response duration were assessed by an independent review committee.

The most common adverse events (AEs) were fatigue (63%), nausea (57%), decreased appetite (37%), and diarrhea (37%). Most AEs were grade 1 and 2. The most common treatment-related AEs were cytopenias and gastrointestinal and constitutional symptoms.

“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, and a paid consultant to Karyopharm.

Because the approval was based on response rate under the FDA’s Accelerated Approval Program, continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Selinexor will become commercially available immediately, according to Karyopharm, which plans to submit a Marketing Authorization Application to the European Medicines Agency in 2021 for the therapy to treat relapsed or refractory DLBCL.

Selinexor is already approved in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma in adults who had received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody.

“…[T]his is now the second commercial oncology indication for Xpovio, highlighting its novel mechanism of action, ease of administration and ability to produce rapid and durable responses in patients with heavily pretreated disease,” Shacham said.