Gene Mutation May Predict Immunotherapy Outcome in Melanoma Patients

Melanoma patients whose tumors had a specific gene mutation demonstrated better response and treatment outcomes when treated with immunotherapies, according to a new study.

Researchers found that among melanoma patients who were treated with immunotherapies, individuals whose tumors had mutations in the NRAS gene responded better to treatment compared to those without the mutation. The study was published in the American Association for Cancer Research’s (AACR) journal Cancer Immunology Research.

“In a retrospective study, we found that patients with NRAS-mutant melanoma seemed to respond better to immunotherapy compared with patients whose tumors had other genetic subtypes, and this was especially true for patients treated with anti-PD-1/PD-L1 therapies,” said Douglas B. Johnson, MD, an assistant professor of medicine at Vanderbilt-Ingram Cancer Center (VICC) in Nashville, TN. “We studied a small group of patients, but the results were quite suggestive. Our findings need to be confirmed in a prospective study.”

Johnson and his team evaluated electronic medical records of 229 melanoma patients treated at VICC, Memorial Sloan Kettering Cancer Center, and Massachusetts General Hospital. Among the patients, 143 received ipilimumab, 58 received IL-2 therapy and 28 received anti-PD-1/PD-L1 drugs as first line therapy. Sixty patients had tumors with NRAS mutations, 53 had BRAF mutations and 116 had the normal forms of these two genes.

They found that 28 percent of patients with NRAS-mutant melanoma had complete or partial responses with the first-line immunotherapy compared with 16 percent who had the normal form of the gene. With anti-PD-1/PD-L1 drugs, the clinical benefit rate was 73 percent for those with NRAS mutations and 35 percent for those with the normal form of the gene. Additionally, patients with NRAS mutations had a trend for better outcome when receiving ipilimumab.

Identifying patients likely to benefit the most from immunotherapies is important to improve treatment outcomes. While immunotherapies have become a main treatment option for melanoma patients, tumor markers can help identify individuals who will benefit the most from these therapies.

“This study highlights the need to find predictive markers that can help us understand which patients will respond to therapy. Our study will hopefully lead to understanding the biological mechanisms that explain why NRAS mutations predict response. We are currently conducting studies to explain this finding,” said Johnson.

Source: American Association for Cancer Research

Last updated: 3/4/15; 12:00pm EST

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