S373 Safety and Predictors of Recurrence in Immune Checkpoint Inhibitor Rechallenge Post-Immune-Mediated Diarrhea and Colitis

Introduction: Immune checkpoint inhibitors (ICIs) are associated with immune-mediated diarrhea and colitis (IMDC), often necessitating treatment interruption. While IMDC is usually manageable with immunosuppression, guidance on ICI resumption remains limited. Rechallenging patients with prior responses yields similar outcomes to non-rechallenged cases, while those without initial responses may experience improved progression-free survival upon resumption. This study evaluates recurrence rates, predictive factors, and potential timing window for ICI rechallenge following IMDC. Methods: This retrospective, single-center study evaluated patients with IMDC between 2015-2025. Statistical analysis included ROC, binary and Cox regression using SPSS 24 (IBM Corp, Armonk, NY). Results: Of 1,128 patients, 58.6% were male and 89.8% White. While 94 patients continued ICI during IMDC, 1,026 discontinued; of these, 309 (30.1%) were later rechallenged after a median of 113 days, with recurrence in 98 (31.7%). IMDC management prior to rechallenge involved corticosteroids alone in 89 patients (Common Terminology Criteria for Adverse Events grade >2 diarrhea and colitis in 74.1% and 43.8%, respectively, recurrence in 20.2%). Corticosteroids plus selective immunosuppressive therapy in 185 patients, with grade >2 diarrhea in 82.7% and colitis in 46.4%; recurrence was 39.5%. Supportive care alone was given to 30 patients, with grade >2 diarrhea and colitis in 34% and 30%, respectively, and recurrence was 16.6%. Three patients received front-line fecal microbiota transplantation, all with grade >2 diarrhea or colitis; no recurrences occurred. ROC and Cox regression did not identify an optimal ICI-free interval to reduce recurrence. However, longer duration of initial IMDC trended toward higher recurrence (hazard ratio: 1.01, confidence interval [CI] :1.0-1.02, P = 0.072), suggesting that event severity may be predictive. On univariate analysis, prior cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor use (odds ratio [OR]: 0.4, CI: 0.2-0.8, P = 0.019) and initial chronic inflammation (OR: 0.3, CI: 0.1-0.9, P = 0.034) were protective, while hospitalization correlated with increased recurrence risk (OR: 2.3, CI: 1.2-4.4, P = 0.011). Conclusion: In this larger single-center cohort, ICI rechallenge after IMDC was feasible, with recurrence in roughly 31.7% of cases. Protective factors included initial CTLA-4 use and chronic inflammation, while hospitalization and longer IMDC index event trended toward increased risk. These findings support a risk-adapted strategies for ICI reintroduction.