SUN-332 Autoimmune Endocrinopathies Associated with CTLA-4 Inhibitors: A Meta-Analysis

Objective: To assess the risks of immune-related endocrinopathies associated with anticytotoxic T-lymphocyte-associated antigen 4 (CTLA4) therapies Methods: Participants who were assigned to treatment with anti-CTLA4 in phase 2 and phase 3 studies were analyzed by meta-analysis. Total eligible studies were 24 (19 on Ipilimumab and 5 on Tremelimumab) Results: Twenty-four studies enrolling 6984 patients were analyzed. Anti-CTLA4 therapy was associated with a significantly higher risk of all grade endocrine related adverse events, Risk Rate (RR) = 0.103, 95% confidence interval (CI) = 0.096- 0.111. Risk rate of Grade 3 and Grade 4 endocrine related adverse events RR = 0.018, 95% CI 0.015-0.021. Anti CTLA4 therapy was also associated with increased risk of hypophysitis, hypothyroidism, hyperthyroidism compared to non-immunotherapy with RR = 0.053,0.052,0.02, 95% CI 0.047-0.058, 0.046-0.057, 0.018-0.025 respectively. The risk of developing hypophysitis was higher in those receiving anti-CTLA4 compared to those who did not receive any immunotherapy (OR= 40.42, 95% CI= 6.20-263.3). Risk of hypophysitis was higher in patients received Ipilimumab (antiCTLA-4) Vs those who received Nivolumab ( anti- Programmed Death inhibitor) (OR = 6.8, 95% CI= 1.96-24.18) Conclusion: Our meta-analysis demonstrates statistically significant increased risk of hypophysitis, hypothyroidism, hyperthyroidism with anti CTLA-4 immunotherapy. Hypophysitis is more commonly seen with anti-CTLA4 compared to anti PD-1. These results would aid the surveillance and management of endocrine-related adverse events in patients receiving anti-CTLA4 immunotherapy.