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.

Association of Blood Biochemical Indexes and Antibiotic Exposure With Severe Immune-related Adverse Events in Patients With Advanced Cancers Receiving PD-1 Inhibitors

“…[15][16][17][18] In a recent study of patients with various cancers receiving ICI treatment, a low level of NLR (< 5.3) was significantly associated with development of irAEs and longer OS. 15 In NSCLC patients treated with anti-PD-(L)1 antibodies, NLR <3 was significantly correlated with irAEs. 16 In addition, a different cohort study revealed that pretreatment with NLR ≥ 5 was associated with worse OS outcomes in patients with NSCLC treated with nivolumab.…”

“…The relationship between NLR, irAE development and outcomes has been reported in several studies. [15][16][17][18] In a recent study of patients with various cancers receiving ICI treatment, a low level of NLR (< 5.3) was significantly associated with development of irAEs and longer OS. 15 In NSCLC patients treated with anti-PD-(L)1 antibodies, NLR <3 was significantly correlated with irAEs.…”

Risk Factors and Biomarkers for Immune-Related Adverse Events: A Practical Guide to Identifying High-Risk Patients and Rechallenging Immune Checkpoint Inhibitors

“…Pre-existing autoimmune disease (AD) and even a family history of it seems to increase the risk of irAE in patients treated with ICI ( 41 – 43 ). Contrary to most studies, a small study with 56 NSCLCs treated with PD-1 inhibitors, the incidence of irAE was not that different from the trials that excluded patients with AD ( 76 ).…”

Comprehensive Statistical Exploration of Prognostic (Bio-)Markers for Responses to Immune Checkpoint Inhibitor in Patients with Non-Small Cell Lung Cancer

“…With respect to irAE, we found a significant cut-off of 0.51 for monocytes, where higher monocyte counts corresponded to an increased odds of developing an irAE. Increased baseline monocyte counts were already associated with the development of irAE in other studies, but also with weak p -values [ 36 ]. We also found monocytes to be significant with respect to the survival random forest for irAE ( Figure 3 ).…”