In the phase 2 STORM Part 1 clinical trial, 21% of patients with refractory multiple myeloma had a partial or better response to oral selinexor (Xpovio) plus dexamethasone. Those findings were the basis for the pivotal phase 2 STORM Part 2 study (Chari A, et al. N Engl J Med. 2019;381:727-738).
This study led to the 2019 FDA approval of selinexor, a selective nuclear export inhibitor that blocks exportin 1, which induces accumulation and activation of tumor suppressor proteins, inhibits nuclear factor κB, and reduces oncoprotein messenger RNA translation.
Part 2 study was a phase 2b, multicenter, open-label clinical trial with 122 patients with multiple myeloma in the United States and Europe; 53% of patients had high-risk cytogenetic abnormalities. Patients received selinexor 80 mg plus dexamethasone 20 mg twice weekly on days 1 and 3 in 4-week cycles until disease progression, treatment discontinuation, or death. Patients had disease refractory to current standard treatment for multiple myeloma.
All patients had previously received ≥3 regimens that included an alkylating agent, bortezomib (Velcade), carfilzomib (Kyprolis), lenalidomide (Revlimid), pomalidomide (Pomalyst), and daratumumab (Darzalex). The primary end point was overall response.
A total of 26 had a response to this combination, which translated to an overall response rate of 25.3% (95% confidence interval, 16.4-36), including 2 stringent complete responses, 6 very good partial responses, and 24 partial responses. By contrast, 39% of the patients had stable disease and 21% had progressive disease or unevaluable disease.
The median duration of response was 4.4 months, the median progression-free survival was 3.7 months, and the median overall survival was 8.6 months. Patients with a minimal response or better had a median overall survival of 15.6 months.
The most common adverse events of grade ≥3 were thrombocytopenia (59%), anemia (44%), hyponatremia (22%), and neutropenia (21%). Overall, 18% of patients discontinued treatment because of adverse events.
The study results were notable for several reasons. The trial was permissive, allowing patients with reduced renal function, thrombocytopenia, and neutropenia to be included. The patients were heavily pretreated, with a median of 7 previous therapeutic regimens, and the patients had rapidly progressing disease, with a 22% increase in disease burden in the 12 days from screening to initial therapy.
“These characteristics are consistent with the growing population of patients who have exhausted available therapies but still desire to continue therapy,” said the investigators.
