Predicting Response to Immunotherapy in Late-Stage Melanoma

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A new model has the potential to identify patients with melanoma who could benefit from treatment with checkpoint inhibitors.
A new model has the potential to identify patients with melanoma who could benefit from treatment with checkpoint inhibitors.

A newly developed molecular predictor may help to identify patients with advanced melanoma who would be the most likely to benefit from treatment with immune checkpoint inhibitors, according to a study published in Nature Medicine.1

The new predictor, IMmuno-PREdictive Score or IMPRES, incorporates the gene-expression features of spontaneous regression in another cancer — neuroblastoma — to determine which patients with late-stage melanoma might respond well to highly tailored antibodies.

Investigators, led by the National Cancer Institute (NCI), developed IMPRES in collaboration with researchers from the University of Pennsylvania, Philadelphia; Harvard University, Cambridge, Massachusetts;  and the University of Maryland, College Park.

“There's a critical need to be able to predict how patients with cancer will respond to this type of immunotherapy,” said Eytan Ruppin, MD, PhD, the lead investigator from the NCI's Center for Cancer Research, in a prepared statement. “Being able to predict who is highly likely to respond and who isn't will enable us to more accurately and precisely guide patients' treatment.”2

In the IMPRES study, the research team analyzed 297 tumor samples from patients with melanoma who had been treated with anti-CTLA-4, anti-PD1, or a combination of the 2 drugs, in 6 independent studies that included 9 different patient datasets. Using IMPRES and a scoring system ranging from 0 to 15, the researchers found that a higher score not only accurately predicted a favorable response 77% to 96% of the time, but also was associated with higher overall patient survival. And, unlike prior predictors, they say, the new system accurately identified immune response patterns between responders and nonresponders across many different patient datasets.

Although checkpoint inhibitors, which target proteins that tumors use to escape detection, have brought stunning success in treating some cancers, these novel immunotherapies — most still being tested in clinical trials — also can overstimulate the immune system, leading to rare, but life-threatening toxicities. That concern led the American Society of Clinical Oncology and the National Comprehensive Cancer Network to announce last year that they would begin issuing guidelines to help physicians manage unexpected or unrecognized events.3

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