Association of blood biomarkers and autoimmunity with immune related adverse events in patients with cancer treated with immune checkpoint inhibitors

Abstract

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. 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), chronic infection and pre-existing systemic steroid use (regardless of dose). Optimal cutoff values of biomarkers were identified by recursive partitioning analysis. 470 patients were identified; 156 (33%) developed irAEs, which were associated with baseline absolute lymphocyte count > 2.6 k/ul (adjusted [a]OR: 4.30), absolute monocyte count > 0.29 k/ul (aOR: 2.34) and platelet count > 145 k/ul (aOR: 2.23), neutrophil to lymphocyte ratio (NLR) ≤ 5.3 (aOR: 2.07) and monocyte to lymphocyte ratio (MLR) ≤ 0.73 (aOR: 2.96), as well as platelet to lymphocyte ratio ≤ 534 (aOR: 5.05). Patients with pre-existing AD (aOR: 2.57), family history of AD (aOR: 5.98), and ICI combination (aOR: 2.00) had higher odds of irAEs. Baseline NLR ≤ 5.3 (aHR: 0.68), MLR ≤ 0.73 (aHR: 0.43), PLT > 145 (aHR: 0.48) and PLR ≤ 534 (aHR: 0.48) were associated with longer OS. irAEs were associated with autoimmune history, ICI combination and baseline laboratory measurements. Lower NLR, MLR and PLR may have favorable prognostic value. Our hypothesis-generating findings require validation in larger prospective studies.

Figure 1

Overall survival (OS) by laboratory cutpoints. Kaplan Meier estimates of OS in patients with (A) absolute lymphocyte count > and ≤ 2.6k/ul, (B) neutrophil to lymphocyte ratio > and ≤ 5.3 (C) monocyte to lymphocyte ratio > and ≤ 0.73, (D) absolute monocyte count > and ≤ 0.29 k/ul, (E) platelent count > and ≤ 145 k/ul and (F) platelet to lymphocyte count > and ≤ 534. aHR adjusted hazard ratio, ICI immune checkpoint inhibitors, ALC absolute lymphocyte count, NLR neutrophil to lymphocyte ratio, MLR monocyte to lymphocyte ratio, AMC absolute monocyte count, Plt platelet count, PLR platelet to lymphocyte count, OS overall survival, CI confidence interval.