S459 Comparative Survival Outcomes and Cluster Effect of Immune-Mediated Colitis and Multisystem Immune-Related Adverse Events in Patients Receiving Immune-Checkpoint Inhibitors

Introduction: Immune-related adverse events (irAEs) associated with immune-checkpoint inhibitors (ICIs) can affect various organ systems. Gastrointestinal (GI) side effects are the most common. Clustering of irAEs refers to grouping AEs based on affected organs, which may impact the patient’s overall outcome. Our study aimed to compare the management and outcomes between patients with IMC alone and those who developed IMC and non-GI irAEs. Methods: This was a single-center, retrospective review. Natural language processing data (NLP) was used to identify keywords from patient electronic health records (EHRs) to screen for irAEs from 2019-2024. GI irAEs were identified by clinical context, stool inflammatory markers, colonoscopy, and histology findings. Non-GI irAEs were reported after ICI initiation within the study window. Variables included but were not limited to patient demographic information, cancer type, ICI regimen, symptoms, lab results, stool tests, treatment, and survival outcomes. SPSS 26.0 (IBM Corp, Armonk, NY) was used to analyze the data. Results: A total of 437 patients with GI irAEs were included, with 251 patients having other irAEs. The most common were endocrine (25.7%), followed by lung (15.5%), and skin (14.2%). Among them, 121 (48.2%) had 2 organ irAEs, and 27 (10.8%) had 3. Immunosuppressive therapy was used in approximately 50-60% of cases with 2 organ systems affected, but 100% among patients with 3 organ irAEs. Biologic therapy was required only among 6 patients (2.4%) for non-Gi irAEs, but 50.3% for GI irAEs alone. Comparatively, CTLA-4-based regimens were associated with more multi-organ irAEs. The survival of patients with multiple irAEs was comparable to patients with colitis alone (2.312 [CI 2.064-2.708] and 2.219 [CI 2.102-2.523]). Conclusion: Our study described the clustering pattern of non-GI irAEs associated with GI irAEs and management strategies. While corticosteroid and biologic regimens were utilized in the majority of patients with GI irAE alone, for non-GI irAEs, steroids were the mainstay of management, with biologics only required in 2.4% of patients. Multi-organ irAEs alongside GI irAEs don’t appear to further impact the long-term survival compared to GI irAEs alone.