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Selinexor regimen induces response in refractory multiple myeloma
A combination of selinexor and dexamethasone induced responses among patients with multiple myeloma refractory to current standard therapies, according to results of the phase 2b STORM study published in The New England Journal of Medicine.
The FDA granted the combination accelerated approval in July for treatment of relapsed or refractory multiple myeloma, based on the results of this study.
“Although the purpose of this study was to demonstrate activity of selinexor in combination with dexamethasone to attain accelerated approvals, multiple myeloma is very genomically complex, and relapsed/refractory myeloma requires combination therapies,” Ajai Chari, MD, director of clinical research in the multiple myeloma rogram at The Tisch Cancer Institute at Mount Sinai Hospital, told HemOnc Today.
Researchers noted that a growing number of patients have triple-class refractory myeloma, which is refractory to proteasome inhibitors, immunomodulatory agents and monoclonal antibodies. Patients resistant to standard treatments have short OS, in some cases less than 3 months.
A potential novel treatment for these patients is selinexor (Xpovio, Karyopharm Therapeutics), a selective nuclear export inhibitor that blocks exportin 1, forces nuclear accumulation and activation of tumor suppressor proteins, inhibits nuclear factor B and reduces oncoprotein messenger RNA translation.
For the multicenter, open-label, phase 2b STORM study, Jagannath and colleagues enrolled 123 patients with triple-class refractory myeloma, all but one of whom was included in the intent-to-treat population (n = 122; median age, 65.2 years; range, 40-86; 58% men). All patients had previous exposure to bortezomib (Velcade, Millennium/Takeda), carfilzomib (Kyprolis, Amgen), lenalidomide (Revlimid, Celgene), pomalidomide (Pomalyst, Celgene), daratumumab (Darzalex, Janssen) and an alkylating agent. More than half of the patients (53%) had high-risk cytogenic abnormalities. Patients had a median myeloma duration of 6.6 years and a median seven (range, 3-18) previous treatment regimens.
All patients received 80 mg oral selinexor and 20 mg dexamethasone twice weekly.
Overall response served as the study’s primary endpoint. Clinical benefit served as a secondary endpoint.
Results showed that 26% of patients (95% CI, 19-35) had a partial response or better, with two achieving stringent complete responses and six demonstrating very good partial responses. Median time to partial response was 4.1 weeks (range, 1-14).
Additionally, 39% of patients had a minimal response or better.
Median duration of response was 4.4 months (95% CI, 3.7-10.8), median PFS was 3.7 months (95% CI, 3-5.3) and median OS was 8.6 months (95% CI, 6.2-11.3). Among patients who had a partial or minimal response or better, median OS was 15.6 months.
Common adverse events, typically grade 1 or grade 2, included fatigue, nausea and decreased appetite. Thrombocytopenia occurred among 73% of patients (grade 3, 25%; grade 4, 33%).
“The addition of other agents to selinexor and dexamethasone, studies of which are already ongoing, will be the way this drug will be used in the future,” Chari said. “Combination therapy also allows the drug to be given at lower dose intensity and, along with optimization of supportive care, this will minimize side effects, allowing patients to remain on therapy and maintain/deepen responses.”
– by John DeRosier
For more information:
Ajai Chari, MD, can be reached at Mount Sinai Ruttenberg Treatment Center, 3rd Floor, New York, NY 10029; email: ajai.chari@mountsinai.org
Disclosures: Chari reports grants or personal fees from Amgen, Bristol Myers Squibb, Celgene, Janssen, Karyopharm, Millenium/Takeda, Novartis Pharmaceuticals, OncoPeptides, Pharmacyclics, Sanofi and Seattle Genetics. Please see the study for all other authors’ relevant financial disclosures.
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