On July 3, 2019, the FDA granted accelerated approval to selinexor (Xpovio; Karyopharm Therapeutics), a nuclear export inhibitor, in combination with dexamethasone, for the treatment of patients with relapsed or refractory multiple myeloma who have received ≥4 previous therapies and did not respond to other forms of treatment, including ≥2 proteasome inhibitors, ≥2 immunomodulatory agents, and an anti-CD38 monoclonal antibody. The FDA reviewed selinexor using its fast track program, and granted it an orphan drug designation.
“While there is no cure for multiple myeloma, there are FDA-approved treatments to target the cancer and slow down the spread of the disease. Sadly, often over time, patients can exhaust all available treatments and still see their disease progress,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence. “Today we approved a treatment under our accelerated approval program that provides a treatment option for patients with multiple myeloma with no available therapy.”
This approval was based on results of the phase 2b STORM clinical trial, of which a prespecified subgroup analysis of 83 patients with relapsed or refractory multiple myeloma that was refractory to treatment with glucocorticoids, a proteasome inhibitor, an immunomodulatory agent, an anti-CD38 monoclonal antibody, and to the last line of therapy. All patients previously received ≥3 treatments, including an alkylating agent, glucocorticoids, bortezomib (Velcade), carfilzomib (Kyprolis), lenalidomide (Revlimid), pomalidomide (Pomalyst), and an anti-CD38 monoclonal antibody. All patients received selinexor plus dexamethasone on days 1 and 3 of every week. Treatment continued until disease progression, death, or unacceptable adverse events.
In the prespecified subgroup analysis, treatment with selinexor plus dexamethasone resulted in an overall response rate of 25.3%, which included 1 stringent complete response, 4 very good partial responses, and 16 partial responses. The median time to first response was 4 weeks, and the median duration of response was 3.8 months.
The most common (≥20%) adverse reactions with selinexor were thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.