Monday , March 8 2021

Selinexor demonstrates significant benefit from previously treated multiple myeloma as a once-weekly regimen | Targeted oncology



Treatment with Selinxor (Xpovio), bortezomib, and dexamethasone (SVd) has been shown to increase the overall response rate (ORR) and progression-free survival (PFS) in patients with multiple myeloma and high cytogenetic risk despite a 40% lower dose schedule. and 25% less dexamethasone during the first 24 weeks of treatment, according to a presentation at the 2020 Annual Meeting of the American Hematology Association.

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

Of the 402 patients enrolled in the Boston study, 192 (48%) had a high risk (SVd, n = 97; Vd, n = 95) and 210 (52%) had a standard risk (SVd, n = 98; Vd, n = 112). ) cytogenetics. The SVd regimen demonstrated improved PFS relative to Vd in high-risk (12.9 vs. 8.1 months; HR, 0.67; 95% CI, 0.45-0.98; P. = 0.0192) and standard risk (16.6 vs. 9.7 months; HR, 0.63; 95% CI, 0.42-0.95; P. = .0131) groups. In addition, the ORR was significantly improved in the high-risk group (77.3% vs. 55.8%, respectively; P. = .0008).

For these post-hoc tests, patients were considered to have a high cytogenetic risk if they were found to have at least the following abnormalities in at least 10% of the plasma cells tested:

  • 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 17p deletions found the greatest benefit, with a PFS of 12.22 months for those receiving SVd regimen versus 5.91 months for those treated with Vd. Patients with 17p deletion also reported 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. Note, the rate of grade 2 or lower peripheral neuropathy was lower with SVd compared with Vd and 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 abnormalities such as 17p deletion, translocation 4; 14 and translocation 4; 16 are still associated with shorter progression-free survival and overall survival than those with standard risk cytogenetic characteristics, ”noted Richard, adding:“ There is an unmet need for new therapies to improve the results of risky cytogenetics in patients with myeloma. The new Selinexor mechanism [of] reactivation of protein suppressors in the tumor and reduction of oncoprotein levels may be particularly beneficial for high-risk diseases.

Reference

Richard, S. Once a week Selinexor, Bortezomib and Dexamethasone (SVd) versus twice a week Bortezomib and Dexamethasone (Vd) in relapsed or refractory multiple myeloma: Cytogenetically planned high-risk subgroups: exhibition by the American Society of Hematology (ASH); December 5-8, 2020. Abstract 1385.


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