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

Treatment with selinexor, bortezomib, and dexamethasone demonstrated an increase in overall response rate and progression-free survival 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.

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.