Selinexor shows efficacy against refractory multiple myeloma
medwireNews: One in five patients with heavily pretreated, refractory multiple myeloma may respond to treatment with the selective exportin 1 (XPO1) inhibitor selinexor, plus low-dose dexamethasone, phase II study findings indicate.
Dan Vogl (University of Pennsylvania, Philadelphia, USA) and colleagues explain that selinexor “induces apoptosis in cancer cells through nuclear retention of tumor suppressor proteins and the glucocorticoid receptor, along with inhibition of translation of oncoprotein [messenger]RNAs.”
They tested its efficacy, at a dose of 80 mg twice weekly, in combination with dexamethasone 20 mg twice weekly, in 48 patients with multiple myeloma refractory to bortezomib, carfilzomib, lenalidomide, and pomalidomide (quad-refractory disease), and in an additional 31 patients whose disease was also refractory to an anti-CD38 antibody (penta-refractory disease).
All patients had previously received glucocorticoid therapy and the majority (97%) had received alkylating agents. Additionally, 41% of participants had been treated with anthracyclines and 77% had undergone autologous stem-cell transplantation. The median number of prior treatment regimens was seven.
As reported in the Journal of Clinical Oncology, the overall response rate (ORR) was 21% and was comparable among patients with quad-refractory (21%) and penta-refractory (20%) disease.
A very good partial response was observed in 5% of patients, while 15% had a partial response. A further 13% had a minimal response, thus yielding a clinical benefit rate of 33%.
The researchers found that patients responded rapidly to treatment, with 85% achieving their minimal response or better within the first 28-day treatment cycle. The median response duration was 5 months, and 65% of responding patients were still alive at 12 months.
The median progression-free and overall survival times were 2.3 and 9.3 months, respectively.
Vogl and team observed a slightly higher ORR, of 35%, among 17 patients with high-risk cytogenetics, including t(4;14), t(14;16), and del(17p).
The adverse effect profile was similar to that observed previously with selinexor in patients with other hematologic cancers. The most common grade 3 or higher adverse events were thrombocytopenia (59%), anemia (28%), neutropenia (23%), hyponatremia (22%), leukopenia (15%), and fatigue (15%).
Just over half (52%) of patients required dose interruptions, 37% needed dose reductions, and 18% discontinued treatment due to adverse events.
Vogl et al describe their findings as “clinically meaningful” and say that “selinexor plus dexamethasone has significant potential to be a new treatment option for patients with refractory myeloma.”
They write: “Selinexor is the first antimyeloma agent to show clear activity in penta-refractory myeloma, a patient population with a high unmet medical need.”
“Although our observed overall response rate of 21% was not statistically significantly higher than our prespecified threshold of 15%, we believe that this evidence of efficacy is sufficient to warrant further study,” they authors conclude.
By Laura Cowen
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