Selinexor Demonstrates Significant Benefit in Pretreated Multiple Myeloma as Once Weekly Regimen

Shambavi Richard, MD

Treatment with selinexor (Xpovio), bortezomib, and dexamethasone (SVd) demonstrated an increase in overall response rate (ORR) and progression-free survival (PFS) in patients with multiple myeloma and high cytogenetic risk despite a dosing schedule that utilized 40% less bortezomib and 25% less dexamethasone during the first 24 weeks of treatment, according to a presentation at the 2020 American Society of Hematology Annual Meeting.

“SVd is superior to Vd in patients with multiple myeloma, including high-risk disease, as supported by the progression-free survival in the different subgroups of patients with high-risk cytogenetics,” said Shambavi Richard, MD, of the Icahn School of Medicine at Mount Sinai. “Once weekly SVd is a highly active regimen, and may be an important treatment option for patients with high-risk multiple myeloma,” Richard added.

Of the 402 patients enrolled in the BOSTON study, 192 (48%) had high-risk (SVd, n = 97; Vd, n = 95) and 210 (52%) had standard-risk (SVd, n = 98; Vd, n = 112) cytogenetics. The SVd regimen demonstrated improved PFS relative to Vd in the high-risk (12.9 vs 8.1 months; HR, 0.67; 95% CI, 0.45-0.98; P = .0192) and standard-risk (16.6 vs 9.7 months; HR, 0.63; 95% CI, 0.42-0.95; P = .0131) groups. Moreover, ORR was significantly improved in the high-risk group (77.3% vs. 55.8%, respectively; P = .0008).

For this post-hoc analyses, patients were deemed to be of high cytogenetic risk if they were found have at least of the following abnormalities in at least 10% of screened plasma cells:

• del(17p)
• t(4;14)
• t(14;16)
• amplification of 1q21

The SVd regimen improved PFS in all high-risk subgroups except t(14;16), which was the smallest subgroup. Patients with a 17p deletion saw the greatest benefit, with a PFS of 12.22 months for those receiving the SVd regimen, vs 5.91 months for those treated with Vd. Patients with a 17p deletion also saw the greatest benefit in terms of ORR (76.2% vs 37.5%; P = .0096).

The safety profiles of SVd and Vd in the high-risk and standard-risk groups were consistent with the overall study population. Of note, the rate of grade 2 or lower peripheral neuropathy was lower with SVd compared with Vd in both the high-risk (25.7% vs 35.7%, respectively; P = .100) and standard-risk groups (18.4% vs. 33.6%, respectively; P = .003).

“Despite recent advances in myeloma, high-risk anomalies such as deletion 17p, translocation 4;14 and translocation 4;16 are still associated with shorter progression-free survival and overall survival relative to those with standard-risk cytogenetic features,” noted Richard, adding “There’s an unmet need for novel therapies to improve outcomes of high-risk cytogenetics in myeloma patients. Selinexor’s novel mechanism [of] reactivating tumor suppressor proteins and reducing levels of oncoproteins may be particularly suited for high-risk disease.”

_Reference

_{Richard, S. Once Weekly Selinexor, Bortezomib, and Dexamethasone (SVd) Versus Twice Weekly Bortezomib and Dexamethasone (Vd) in Relapsed or Refractory Multiple Myeloma: High Risk Cytogenetic Planned Subgroup Analyses from the Phase 3 BOSTON Study. Presented at: 62nd American Society for Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 1385.}