Predictive biomarkers for immune-related adverse events in cancer patients treated with immune-checkpoint inhibitors

Abstract

Purpose The objective of this study was to identify potential predictors of immune-related adverse events (irAEs) in cancer patients receiving immune checkpoint inhibitor therapy among serum indexes, case data, and liquid biopsy results. Methods We retrospectively analyzed 418 patients treated with anti-programmed cell death 1(PD-1)/PD-1 ligand (PD-L1) inhibitors from January 2018 to May 2022 in our cancer center. We identified factors that correlated with the occurrence of irAEs and evaluated associations between irAEs and anti-PD-1/PD-L1 inhibitor responses. Results The incidence of irAEs was 42.1%, and pneumonitis (9.1%), thyroid toxicity (9.1%), cardiotoxicity (8.1%), and dermatologic toxicity (6.9%) were the four most common irAEs. Multivariate logistic analysis identified female sex, antibiotic use, higher post-treatment neutrophil-to-lymphocyte ratio (NLR), and higher baseline circulating tumor cell (CTC) level, as predictive biomarkers for the occurrence of irAEs. A lower baseline prognostic nutritional index (PNI), body mass index (BMI) ≥ 25 kg/m2, and higher post-treatment lactate dehydrogenase (LDH) level were predictive factors for more severe irAEs (higher severity grade). Patients without irAEs had better overall survival than those with irAEs. Specifically, pneumonitis and cardiotoxicity were found to be significant predictors of poor prognosis in the irAE subgroup with different organ-related irAEs. Low-dose steroid (dexamethasone 10 mg) treatment had no significant effect on outcomes. Conclusions Gender, antibiotic use, post-treatment NLR, and baseline CTC level are potential predictive biomarkers of irAEs, while baseline PNI, BMI, and post-treatment LDH may predict the severity of irAEs. The predictive effect of irAE occurrence on survival benefit may depend on the type of irAE.

Prognostic value of body mass index for first-line chemoimmunotherapy combinations in advanced non-small cell lung cancer in Chinese population

“…Additionally, anthropometric measurements such as waist circumference and waist-hip ratio, as well as image-based measures such as computed tomography or magnetic resonance imaging can be used to characterize obesity as well; however, they could not be obtained from medical records in this study and may be collected prospectively in the follow-up [ 17 , 45 , 46 ]. Finally, it has been shown that BMI is positively correlated with the incidence of immune-related adverse events (irAE) [ 47 ]; however, since this study focused on the relationship between BMI and prognosis of chemoimmunotherapy combinations, the analysis regarding irAE was not performed, but we plan to do so in a follow-up study.…”

Uncommon Adverse Events of Immune Checkpoint Inhibitors in Small Cell Lung Cancer: A Systematic Review of Case Reports

“…Despite considerable efforts by investigators to develop biomarkers for predicting irAEs, a reliable and definite indicator remains elusive to date [86]. Nevertheless, with ongoing research aimed at creating tools that improve predictions by integrating multiple indicators, it is anticipated that forthcoming research will enhance predictive precision through more comprehensive and sophisticated studies [87].…”