S374 Survival Outcomes in Immune-Mediated Diarrhea and Colitis Patients Treated With Fecal Microbiota Transplantation and Selective Immunosuppressive Therapy

Introduction: Response rates to immune checkpoint inhibitors (ICI) vary widely—15%–30% in most solid tumors and 45%–60% in melanoma. Fecal microbiota transplantation (FMT) from ICI responders is under investigation to improve outcomes in non-responders by modulating their microbiome. Additionally, FMT from healthy donors has been used to treat immune-mediated diarrhea and colitis (IMDC). This study evaluates whether FMT from healthy donors can influence cancer progression or survival in IMDC patients compared to standard selective immunosuppressive therapy (SIT) alone. Methods: This retrospective single-center study included IMDC patients enrolled in NCT04407247 (Group 1: corticosteroids + SIT) and NCT03819296 (Group 2: corticosteroids + SIT + FMT). Statistical analysis was performed using SPSS v24 (IBM Corp, Armonk, NY). Results: Ninety-eight patients were included: 42 in Group 1 and 54 in Group 2. Baseline characteristics and intergroup comparisons are detailed in Tables 1 and 2. Multivariate logistic regression showed that a higher number of ICI doses prior to IMDC was protective against cancer progression (odds ratio [OR]: 0.9, P = 0.047), with a trend favoring PD-1/PD-L1 therapy (OR: 0.05, P = 0.099). Initiation of new chemotherapy within 6 months of toxicity onset was associated with cancer progression (OR: 11.9, P = 0.001). Cox multivariate analysis identified increased mortality linked to resumption of initial chemotherapy post-IMDC (hazard ratio [HR]: 28.4, P = 0.013) and initial infliximab use (HR: 22.1, P = 0.033) for IMDC. Higher number of SIT doses were significantly associated with improved survival (HR: 0.2, P = 0.040). Kaplan-Meier analysis indicated a trend toward longer survival in the SIT + FMT group versus SIT alone (mean 60.2 vs 28.7 months; P = 0.097). Vedolizumab was associated with significantly longer survival (mean 55.0 months) compared to infliximab (mean 26.7 months; P = 0.016). Conclusion: This study suggests that treatments e.g. SIT and FMT could improve the IMDC condition, but do not promote cancer progression. Vedolizumab was independently associated with better survival than infliximab. Adding FMT to SIT may improve survival further in IMDC patients. These findings warrant further research.