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The United Kingdom’s Medicines & Healthcare Products Regulatory Agency has granted conditional marketing authorization to the combination of selinexor and dexamethasone as a treatment for select patients with relapsed/refractory multiple myeloma.
The United Kingdom’s Medicines & Healthcare Products Regulatory Agency has granted conditional marketing authorization to the combination of selinexor (Nexpovio) and dexamethasone as a treatment for select patients with relapsed/refractory multiple myeloma.1
The combination is indicated for patients who have previously received at least 4 therapies; whose disease is refractory to at least 2 proteasome inhibitors (PIs), 2 immunomodulatory (IMiD) drugs, and an anti-CD38 monoclonal antibody; and who have experienced progressive disease on their last therapy.
The authorization is supported by findings from the phase 2b STORM trial (NCT02336815), in which the selinexor regimen elicited an overall response rate (ORR) of 26% (95% CI, 19%-35%) in this heavily pretreated population; this included 2 stringent complete responses (in 2%), 6 very good partial responses (PRs; in 5%), and 24 partial responses (in 20%).2
Continued authorization is dependent upon the verification of clinical benefit with the doublet in a confirmatory trial and is subject to additional monitoring.
A total of 123 adult patients with heavily pretreated, triple-class refractory multiple myeloma were enrolled to the international, multicenter, single-arm, open-label phase 2b STORM trial.
To be eligible for enrollment, patients needed to have measurable disease and have received prior bortezomib (Velcade), carfilzomib (Kyprolis), lenalidomide (Revlimid), pomalidomide (Pomalyst), daratumumab (Darzalex), glucocorticoids, and an alkylating agent. Patients also needed to have disease that was refractory to at least 1 IMiD, 1 PI, daratumumab, glucocorticoids, and their most recent regimen.
The median age of these patients was 65.2 years and 53% had high-risk cytogenetic abnormalities. Participants had previously received a median of 7 treatments, including a median of 10 unique anti-myeloma drugs.
Participants received oral selinexor at a dose of 80 mg plus 20 mg of dexamethasone on days 1 and 3, on a weekly basis, in 4-week treatment cycles. They received treatment until either progressive disease, death, or discontinuation. All participants received 8 mg of ondansetron prior to study treatment initiation, and 2 or 3 times daily, as needed. Patients with unacceptable toxicities with ondansetron were allowed to received other antiemetics.
The primary end point of the trial was ORR, while secondary end points comprised duration of response; clinical benefit, defined as a confirmed minimal response or better; progression-free survival; and overall survival.
Additional data published in the New England Journal of Medicine indicated that a minimal response per the International Myeloma Working Group criteria was experienced by 13% of patients (n = 16). Moreover, 39% of patients achieved stable disease with the combination. All responses were adjudicated by an Independent Review Committee.
The median DOR was 4.4 months (95% CI, 3.7-10.8) with selinexor plus dexamethasone. Moreover, the median PFS was 3.7 months (95% CI, 3.0-5.3) with the doublet, while the median OS was 8.6 months (95% CI, 6.2-11.3). In those who achieved a PR or better, or a minimal response or better, the median OS was 15.6 months.
The most frequently reported toxicities that were experienced by 20% or more patients who received the doublet, included thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection. Twenty-seven percent of patients discontinued treatment because of toxicities.
Previously, in March 2021, selinexor plus dexamethasone was granted conditional marketing authorization by the European Commission for the same indication based on data from STORM.3