FMT Enhances Immunotherapy Response While Influencing Toxicity Profiles in Lung Cancer and Melanoma

In the FMT-LUMINATE trial, patients with advanced NSCLC receiving ⍺PD-1 and melanoma patients treated with dual ICI underwent fecal microbiota transplantation (FMT) from healthy donors, resulting in high objective response rates (80% in NSCLC and 75% in melanoma) with distinct microbiome shifts; responders showed increased polyamines, bile salts, and activated immune cell populations, while a donor profile high in Prevotella copri was linked to increased grade >3 immune-related adverse events in melanoma.

Personalizing immunotherapy through microbiome modulation could enhance efficacy and mitigate toxicity, making FMT a promising adjunct to ICI regimens in diverse cancer settings.