Treatment and outcomes of immunotherapy related colitis and hepatitis- a multi-centre cohort study in the United Kingdom by the National Oncology Trainee Collaborative for Healthcare Research (NOTCH)

PURPOSE: Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of many cancers but are associated with immune-related adverse events (irAEs), including gastrointestinal toxicities such as colitis and hepatitis. This study aimed to evaluate the incidence of GI-irAEs, identify risk factors for their development, and assess the relationship between GI-irAEs, immunosuppressive treatment, and overall survival (OS) in a large real-world cohort. METHODS: A multi-centre retrospective study was conducted across 12 National Health Service centres in the United Kingdom between June 2016 and 2018. Consecutive adult patients receiving ICIs for malignant melanoma, non-small cell lung cancer, or renal cell carcinoma were included. Clinically significant (≥ grade 2) GI-irAEs were recorded. Logistic regression was used to identify predictive factors for GI-irAEs and immunosuppressant (IS) use. OS was assessed using Kaplan-Meier survival analysis and log-rank testing. RESULTS: A total of 2,049 patients were included, of whom 1,649 were included in the GI-irAE subgroup analysis. Colitis occurred in 191 (9.3%) patients and hepatitis in 142 (6.9%). The majority of patients were treated with steroids alone; 22.3% of colitis cases and 15.8% of hepatitis cases required second line IS. Colitis and hepatitis were both associated with improved OS compared to patients without irAEs (p < 0.0001). Pre-existing autoimmune disease and combination immunotherapy predicted IS use in colitis, while grade 2-3 hepatitis predicted IS use. IS did not significantly affect OS in colitis but was associated with improved OS in hepatitis. CONCLUSION: Colitis and hepatitis are common GI-irAEs following ICI therapy and are associated with improved OS. The use of IS does not negatively impact survival, supporting their continued use in the management of steroid-refractory GI-irAEs and informing supportive care strategies for risk stratification and optimisation of toxicity management in patients receiving immunotherapy.