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Study Identifies Three-Gene Signature That May Predict Response to Selinexor in Patients With Multiple Myeloma


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Researchers have, for the first time, identified genes that may predict response to a therapy for a blood cancer that can have serious side effects for some patients. The therapy, selinexor, is part of the treatment armamentarium for multiple myeloma, but the ability to target its use to patients who would benefit the most remained elusive until now, according to a study published by Restrepo et al in JCO Precision Oncology.

Scientists sequenced RNA from patients with multiple myeloma treated with selinexor, and identified a signature of three genes that were activated in patients who had positive responses. They validated the signature in an independent group of patients who participated in an international clinical trial that led to U.S. Food and Drug Administration (FDA) approval of the drug.

“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,” said co-senior author of the study, Alessandro Laganà, PhD, Assistant Professor of Oncological Sciences at The Tisch Cancer Institute at Mount Sinai and Assistant Professor of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai.

Samir Parekh, MD, Director of Translational Research in Myeloma at The Tisch Cancer Institute at Mount Sinai, and the other co-senior author of the study, added, “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 (CAR) T-cell therapy, an increasingly important clinical challenge in myeloma.”

Selinexor has proven helpful for patients who failed other FDA-approved therapies for multiple myeloma. However, the majority of patients who take the drug experience side effects, sometimes severe, so it is important to identify patients who will respond positively and potentially expand the use of the drug into patients who haven’t failed other therapies.

Mount Sinai researchers identified the three genes—WNT10A, DUSP1, and ETV7—by sequencing samples from about 100 patients with multiple myeloma who received the drug. They also found the three-gene signature in patients with glioblastoma who responded well to selinexor.

As a result of this study, the research team has begun to further study tests for this signature to identify patients who may benefit from selinexor in patients who qualify to use the drug, as well as patients who participate in a precision medicine clinical trial launching soon.

Disclosure: For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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