Association of Blood Biochemical Indexes and Antibiotic Exposure With Severe Immune-related Adverse Events in Patients With Advanced Cancers Receiving PD-1 Inhibitors
Lijun Zhao, Yang Li, Ning Jiang, Xue Song, Jianhua Xu, Xiangzhi Zhu, Cheng Chen, Cheng Kong, Xiaohua Wang, Dan Zong, Luan Li, Cen Han, Li Yin, Xia He
Abstract
Some patients with cancer treated with programmed death 1 (PD-1) inhibitors experience immune-related severe adverse events (ir-SAEs), however, predictors are limited. The objective was to identify clinicopathologic features that may be associated with a higher ir-SAE risk. This was a nested case-control study. After screening a total of 832 PD-1 inhibitor-treated patients, we identified 42 ir-SAE cases. According to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, ir-SAEs were defined as grade ≥3 toxic effects associated with immunotherapy. A total of 126 controls were matched. The crude and adjusted risks of ir-SAEs were estimated by odds ratio (ORs) and 95% CIs using multivariate logistic regression models. Baseline neutrophil-to-lymphocyte ratio (NLR) [per SD increment-adjusted (aOR): 1.16], lactate dehydrogenase (LDH) ≥245 U/L (aOR: 2.39), and antibiotic exposure (aOR: 4.39) were associated with a higher risk of ir-SAEs. When NLR was categorized in 3 groups, significantly higher risks of ir-SAEs (aOR: 4.95) were found in participants in group 3 (>6) than in those in group 1 (<3). Furthermore, NLR (per SD increment-adjusted hazard ratio:1.08) were also significantly associated with shorter overall survival (OS). Baseline LDH ≥245 U/L and antibiotic exposure were no significant association with OS. In conclusion, ir-SAEs were associated between baseline NLR, LDH ≥245 U/L and antibiotic exposure. Lower NLR was correlated with longer OS for cancer.