Deciphering and modifying the composition of various gut bacteria may improve immune checkpoint blockade (ICB) treatment responses in patients with advanced melanoma, according to a paper presented on April 8, 2024, at the annual meeting of the American Association for Cancer Research in San Diego, Calif.
In this study, researchers from the University of Texas MD Anderson Cancer Center in Houston evaluated selected specific groups of bacteria in a placebo-controlled, randomized biomarker-driven trial studying the effect of the gut microbiome on nivolumab therapy.
The small study followed 14 patients who received either the oral antibiotic vancomycin plus SER-401, a bacterial consortia enriched for Firmicutes spores and Ruminococcaceae, or placebo, followed by nivolumab (n=8 vancomycin+SER-401, n=6 placebo). According to the authors, pre-conditioning with vancomycin was associated with significant shifts in the microbiome taxonomic composition of the gut.
The authors noted there was a significant increase in multiple ICB-resistance-associated pathways (e.g., butyrate synthesis, p<0.0001), and a decrease in response-associated pathways after preconditioning with vancomycin. These changes, they noted, returned to normal by the time nivolumab therapy was initiated.
Based on the study results, the placebo arm had a higher overall response rate (66.7%) and disease control rate (83.3%) compared to the vancomycin+SER-401 treatment arm (25.0% and 37.5% respectively). The reason a lower rate in the treatment arm is considered a positive outcome, in this case, is that the goal of the study was to evaluate the safety and efficacy of the SER-401 microbiome intervention in combination with nivolumab.
According to the researchers, the results indicate that patients with advanced melanoma who are resistant to ICB therapy alone may benefit from a combination approach that includes modulating the gut microbiome. They note the results suggest the SER-401 intervention may not have been as effective as hoped in enhancing the anti-tumour response to nivolumab in this patient population, but the lower rates in the treatment arm are considered positive because it indicates the SER-401 intervention did not negatively impact the efficacy of the nivolumab therapy, even though it did not provide the expected benefit.
The researchers report the key positive finding is that the SER-401 intervention was well-tolerated, with no Grade 3-4 treatment-related adverse events reported. This supports the safety of the microbiome-based approach, even though the efficacy results were not as favourable as the placebo arm. Further research is needed to determine how specific optimization of the microbiome could improve outcomes with nivolumab, compared to nivolumab alone.
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