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).

内容摘要

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. 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 (&#x2265;&#x2009;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. 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&#x2009;<&#x2009;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. 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.