Pre-existing autoimmune disease as a risk factor for immune-related adverse events in cancer patients receiving immune checkpoint inhibitors

Abstract Immune checkpoint inhibitors (ICIs) are widely used for cancer treatment, but approximately 30% of cases experience immune-related adverse events (irAEs). Patients with pre-existing autoimmune diseases (AIs) are often advised against ICIs due to the higher risk of irAEs. However, there hasn't been sufficient risk assessment for AIs. We analyzed 478 cases receiving anti-PD-(L)1 Ab and/or anti-CTLA4 Ab at our hospital between April 2017 and May 2022, of which 28 (5.9%) had pre-existing AI. We analyzed the odds ratio (OR) of gender, age, performance status, cancer type, ICI type, combined agents, best overall response, and pre-existing AI using logistic regression. The results showed that pre-existing AI increased the risk of irAE occurrence (OR: 2.52, p = 0.033) and ICI discontinuation due to irAE (OR: 3.32, p = 0.006). Patients with AI had shorter irAE-free survival (median: 5.7 months) compared to those without AI (10.4 months) (p = 0.035). Frequent irAEs; dermatitis, pneumonitis, hepatitis, and hypothyroidism, were often associated with pre-existing AI. AI flared up in 6 cases (37.5%). AI activity didn't affect irAE occurrence. Grade 3 or higher irAEs were seen in 6 out of 21 (28.6%) AI cases with irAEs. Although complicated AI increases the risk of irAEs, closely monitoring patients may allow ICI treatment.