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Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Posted: Wednesday, July 27, 2022
Researchers at Mount Sinai have identified a novel three-gene expression signature that may predict response to selinexor-based therapy in patients with multiple myeloma, according to a study published in JCO Precision Oncology. “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 [chimeric antigen receptor T-cell therapy], an increasingly important clinical challenge in myeloma,” stated Samir Parekh, MD, of The Tisch Cancer Institute at Mount Sinai, New York, in a Mount Sinai press release.
In this study, the authors performed RNA sequencing, differential gene expression, and pathway analysis on CD138-positive cells from the bone marrow of 100 patients with multiple myeloma who participated in the BOSTON study. With the differentially expressed genes that were identified, they used Cox proportional hazard models to develop a gene signature predictive of response to selinexor (a selective inhibitor of nuclear export).
The three genes identified in the signature—WNT10A, DUSP1, and ETV7—were “robustly validated” in 64 patients from the STORM cohort of triple-class–refractory multiple myeloma and in an external cohort of 35 patients treated in a real-world setting outside of clinical trials. The signature appeared to track both the depth and the duration of response. Additionally, the gene signature was validated in a different tumor type using a cohort of pretreatment tumors from patients with recurrent glioblastoma.
Based on the genes involved in the signature, the authors hypothesized that upregulated interferon-mediated apoptotic signaling may prime tumors to respond to selinexor-based therapy. “This signature has important clinical relevance, as it could identify patients with cancer who are most likely to benefit from treatment with selinexor-based therapy,” concluded the study authors.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
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