Risk factors for immune mediated adverse events with immune checkpoint inhibitors.

2622 Background: Immune checkpoint inhibitors (ICIs) are associated with unique toxicity - immune-related adverse events (irAEs). irAEs are common, occurring in nearly 30 % of patients (pts) in clinical trials. Risk factors for irAEs remain largely unknown, with limited evidence to guide risk stratification for these pts. Methods: In this historical cohort study, we identified 400 pts receiving ICIs at our institution between 1/1/2015 - 12/31/2019 and followed them until progression, death, or study end date. Using modified Poisson and multinomial logistic regression we assessed irAEs (yes/no; none/grade 1-2/grade 3-4) as a function of independent risk factors in separate models. These included age, PDL-1%, steroid use in the 2 weeks (S2wks) prior to ICI, concurrent chemotherapy, combination ICI use, and pre-ICI creatinine (Cr) and absolute lymphocyte count. We constructed sample weights using sociodemographic and clinical factors to account for confounding by indication and mortality-related censoring. Results: 367 pts (median age: 68 yrs) had complete data for analysis comprising 55% men and 89% white. 111 (31%) experienced an irAE during the study period (median time to first event: 81 days). Risk was greatest for the youngest and oldest pts on ICI. In weighted models, Pts ≤59 yrs were 3 times as likely to experience an irAE relative to those aged 60-68 (95% CI: 1.18,7.41; Table). Additionally, for each 1 unit increase in Cr, risk of irAE increased by 19% (95% CI: 1.08,1.28). Precision of weighted estimates was impacted by limited pt comparability across factors of interest and overall sample size. While not statistically significant (RR: 2.04;95% CI:0.92,4.53) 70.6% of pts on combination ICIs experienced an irAE compared with 20.3% on one ICI. Similarly, while not statistically significant, 15.4% of pts with PDL-1 >49% experienced a grade 3/4 irAE compared with 7.7% of pts with PDL-1<1%. Conclusions: In this real-world analysis of irAEs, younger age and elevated creatinine were risk factors for development of irAEs. Further research leveraging larger data sources is needed to examine PDL-1% as a potential risk factor of irAE.[Table: see text]