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The China National Medical Products Administration has granted a conditional marketing approval to selinexor for use in combination with dexamethasone in patients with relapsed or refractory multiple myeloma who have previously received treatment and whose disease is refractory to at least a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
The China National Medical Products Administration has granted a conditional marketing approval to selinexor (Xpovio) for use in combination with dexamethasone in patients with relapsed or refractory multiple myeloma who have previously received treatment and whose disease is refractory to at least a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody.1
The regulatory decision was supported by findings from the phase 2 STORM trial (NCT02336815) and data from the phase 2 MARCH trial that was conducted in China and examined the safety and efficacy of the first-in-class SINE compound in combination with dexamethasone in patients with relapsed or refractory multiple myeloma.
Data from STORM indicated that the selinexor regimen elicited an overall response rate (ORR) of 26% (95% CI, 19%-35%) in this heavily pretreated population. Among those who responded to treatment, 2 had stringent complete responses, 6 experienced very good partial responses (PR), and 24 achieved partial responses.2
The phase 3 BENCH trial, which is examining selinexor in combination with bortezomib (Velcade) and low-dose dexamethasone in patients with multiple myeloma as early as first relapse, will serve as the confirmatory trial for the regulatory decision.
“There is no cure for multiple myeloma, and over time, patients stop responding to available treatments,” Richard Paulson, president and chief executive officer of Karyopharm Therapeutics, Inc., stated in a press release. “The approval of [selinexor] in China offers patients with relapsed multiple myeloma a new therapeutic option and the first in a new class of therapeutics, to improve outcomes for patients. We remain committed to expanding access to selinexor across the global with each additional ex-US approval of selinexor and look forward to working closely with Antengene to bring [selinexor] to patients in China.”
The global, multicenter, single-arm, open-label STORM trial enrolled a total of 123 adult patients with heavily pretreated, triple-class refractory multiple myeloma. These patients had measurable disease and previously received bortezomib, carfilzomib (Kyprolis), lenalidomide (Revlimid), pomalidomide (Pomalyst), daratumumab (Darzalex), glucocorticoids, and an alkylating agent. Moreover, patients had disease that was refractory to at least 1 IMiD, 1 PI, daratumumab, glucocorticoids, and the most recent regimen they had received.
The median age of study participants was 65.2 years, and approximately half (53.0%) had high-risky cytogenetic abnormalities. The median number of prior lines of treatment received was 7, and this included a median of 10 unique anti-myeloma agents.
Oral selinexor was administered at a dose of 80 mg in combination with dexamethasone at 20 mg on days 1 and 3 weekly in 4-week cycles. Treatment was given until disease progression, death, or discontinuation. All patients received ondansetron at 8 mg before the initiation of study treatment, and 2 or 3 times daily, as needed. Patients who had intolerable toxicities with this agent were permitted to receive other antiemetics.
The primary end point of the trial was ORR, and key secondary end points comprised duration of response (DOR), clinical benefit defined as confirmed minimal response or better, progression-free survival (PFS), and overall survival (OS).
Additional findings from the trial revealed that 13% of patients (n = 16) achieved a minimal response to treatment per International Myeloma Working Group criteria. Also, 39% of patients had stable disease with the doublet, and all responses were adjudicated by an independent review committee.
Moreover, the median DOR with the selinexor regimen was 4.4 months (95% CI, 3.7-10.8), the median PFS was 3.7 months (95% CI, 3.0-5.3), and the median OS was 8.6 months (95% CI, 6.2-11.3). Among those who experienced a PR or better to treatment, or a minimal response or better, the median OS was higher, at 15.6 months.
Thrombocytopenia, fatigue, nausea, decreased appetite, reduced weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection, were among the most frequently reported toxicities with the combination. Twenty-seven percent of patients ended up discontinuing treatment due to these adverse effects.
In June 2021, the United Kingdom’s Medicines & Healthcare Products Regulatory Agency granted conditional marketing authorization to selinexor and dexamethasone in the treatment of select patients with relapsed or refractory multiple myeloma.3 In March 2021, selinexor plus dexamethasone was granted a conditional marketing authorization by the European Commission for use in select patients with relapsed/refractory disease.4
In July 2019, the FDA granted an accelerated approval to the selinexor combination for use in adult patients with relapsed/refractory multiple myeloma who received 4 or more prior therapies and whose disease was refractory to at least 2 PIs, 2 IMiDs, and a CD38-targeted monoclonal antibody.5 The decision was supported by data from part 2 of the STORM trial.