Gut microbiome patterns predict melanoma recurrence after immunotherapy

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The composition of gut bacteria can predict which melanoma patients will experience cancer recurrence after surgical resection and immunotherapy, but only when matched to patients with similar microbial profiles, according to research published April 17 in Cell. The findings from a 674-patient international clinical trial offer a novel approach to stratifying recurrence risk in high-risk melanoma patients undergoing adjuvant immune checkpoint blockade.

Researchers from NYU Langone Health and Perlmutter Cancer Center analyzed stool samples from participants in the CheckMate 915 trial, which compared combination nivolumab plus ipilimumab with nivolumab monotherapy across five geographic regions. Despite adjuvant immune checkpoint blockade, 25 to 40% of melanoma patients experience recurrence after surgical resection, but predicting which patients will relapse has remained clinically challenging.

The study identified key bacterial taxa associated with recurrence risk, including Eubacterium, Ruminococcus, Firmicutes, and Clostridium. When patients were stratified by overall gut microbiome similarity using Jensen-Shannon divergence measurements, these bacterial markers predicted recurrence with 83 to 94% accuracy depending on geographic region.

“Our study identified for the first time gut bacterial types that can serve as markers of increased recurrence risk in these specific patients, which will help tailor treatment,” said study senior author Jiyoung Ahn, PhD, professor in the Department of Population Health at NYU Grossman School of Medicine, in a press release.

The critical finding was that bacterial signatures derived from one geographic region could accurately predict recurrence in patients from other regions only when those patients exhibited similar baseline microbiome profiles. “Past studies have struggled because the gut bacteria that predict treatment success seemed to change from one region to another,” said Dr. Ahn. “Our study provides a new method that overcomes this barrier, showing that these markers are indeed generalizable if we account for the person's underlying microbiome.”

The gut microbiome composition remained stable throughout the yearlong immunotherapy course, suggesting a single pretreatment microbiome analysis could provide reliable prognostic information. “This means that a single pretreatment microbiome test could provide a reliable forecast of a patient's risk,” added study author Richard B. Hayes, DDS, PhD, MPH. “The next step is to validate this matching approach in other cancers and to build the diverse databases needed to make this approach clinically feasible.”