Association of Blood Biomarkers and Autoimmunity with Immune Related Adverse Events in Patients with Cancer treated with Immune Checkpoint Inhibitors

Background: Patients with cancer treated with immune checkpoint inhibitors (ICIs) develop immune related adverse events (irAEs), however biomarkers are lacking. We hypothesized that clinicopathologic and laboratory factors would be associated with irAE risk and overall survival (OS) in this population. Methods: : In a retrospective study of patients treated with ICIs we collected clinicopathologic, laboratory, irAEs and outcomes data. The association between baseline blood biomarkers, clinicopathologic features and irAEs was assessed by logistic regression adjusting for age, sex, smoking, cancer type, performance status, concomitant other systemic therapy, history of autoimmune disease (AD) and chronic infection. Optimal cutoff values of biomarkers were identified by recursive partitioning analysis. Results: : 470 patients were identified; 156 (33%) developed irAEs, which were associated with baseline absolute lymphocyte count >2.6k/ul (adjusted [a]OR:4.12), neutrophil to lymphocyte ratio (NLR) ≤5.3 (aOR:2.08) and monocyte to lymphocyte ratio (MLR)≤0.73 (aOR:3.11). Patients with pre-existing AD (aOR:2.81), family history of AD (aOR:5.86), and ICI combination (aOR:2.26) had higher odds of irAEs. Baseline NLR≤5.3 (aHR:0.68) and MLR≤0.73 (aHR:0.43) were associated with longer OS. Conclusion: irAE were associated with autoimmune history, ICI combination and baseline laboratory measurements. Lower NLR and MLR may have favorable prognostic value. Our hypothesis-generating findings require validation in larger prospective studies.