Three-Gene Signature Predicts Response to Selinexor in MM

A three-gene signature could identify patients with relapsed/refractory multiple myeloma (MM) who may benefit from the drug selinexor, according to research published in JCO Oncology.

“This signature has important clinical significance, as it could identify patients who are most likely to benefit from treatment with selinexor-based therapy, especially in earlier lines of therapy,” Alessandro Lagana, PhD, a senior author on the paper and assistant professor of oncological sciences at The Tisch Cancer Institute at Mount Sinai, said in a statement.

Until the discovery of the genetic signature, consisting of the genes WNT10A, DUSP1, and ETV7, there were no known biomarkers or assays to help select patients with MM who would benefit from selinexor therapy.

The authors also wrote that the three genes “reveal a potential mechanism through upregulated interferon-mediated apoptotic signaling that may prime tumors to respond to selinexor-based therapy.”

Researchers performed RNA sequencing on DC138+ cells from the bone marrow of 100 patients with MM who participated in the phase III BOSTON study. RNA sequencing and analysis of the differential gene expressions and pathways led to the identification of the three-gene signature.

Researchers then validated the signature in two cohorts: patients with MM treated with selinexor and dexamethasone who participated in the phase II STORM trial (n=64) and patients with MM treated post-U.S. Food and Drug Administration approval at Mount Sinai Hospital outside of any clinical trial setting (n=35).

“Our findings provide the basis for improving patient selection for targeted agents using a small panel of genes to guide precise application of these drugs in real world scenarios, including relapse following CAR-T, an increasingly important clinical challenge in Myeloma,” Samir Parekh, MD, of the Tisch Cancer Institute at Mount Sinai, said.

Restrepo P, Bhalla S, Ghodke-Puranik Y, et al. A three-gene signature predicts response to selinexor in multiple myeloma. JCO Precis Oncol. 2022. doi:10.1200/PO.22.00147