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. 2025 Jul 15;17(7):4976-4985.
doi: 10.62347/EUHL7337. eCollection 2025.

Hematological parameters as predictors of immune-related adverse events: risk factor analysis in non-small cell lung cancer patients undergoing immunotherapy

Yong Jia  1 , Rong Wang  2 , Junlong Shen  1 , Yingying Wang  3
Affiliations

Hematological parameters as predictors of immune-related adverse events: risk factor analysis in non-small cell lung cancer patients undergoing immunotherapy

Yong Jia et al. Am J Transl Res. .

Abstract

Objective: To evaluate the predictive value of hematological biomarkers in assessing the risk of immune-related adverse events (irAEs) in non-small cell lung cancer (NSCLC) patients undergoing immunotherapy and to identify potential risk factors for personalized treatment optimization.

Methods: Clinical data of 274 NSCLC patients who received immunotherapy between April 2018 and January 2021 were retrospectively analyzed. Patients were divided into irAEs and non-irAEs groups based on the occurrence of irAEs. Peripheral blood indices within one week before treatment initiation were assessed and compared, including absolute neutrophil count (ANC), lymphocyte count (LYM), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), albumin-to-alkaline phosphatase ratio (AAPR), and albumin-to-fibrinogen ratio (AFR). Kaplan-Meier analysis compared overall survival (OS) and progression-free survival (PFS), while logistic regression identified independent risk factors for irAEs. Receiver operating characteristic (ROC) curve analysis evaluated predictive performance.

Results: Among the 274 patients, 116 (42.2%) developed irAEs. Compared to the non-irAEs group, the irAEs group exhibited significantly higher ANC, NLR, PLR, and SII, along with lower LYM, AAPR, and AFR as well as lower OS and PFS rates (all P < 0.05). Logistic regression showed that all hematological indicators were independent risk factors for irAEs (P < 0.05). ROC analysis showed an AUC of 0.722 for NLR and 0.829 for the combined model.

Conclusion: Pretreatment assessment of ANC, LYM, NLR, PLR, SII, AAPR, and AFR provides valuable predictive utility for irAEs risk in NSCLC patients undergoing immunotherapy. Integrating these biomarkers into clinical practice may enhance risk stratification and guide personalized treatment strategies to improve safety and therapeutic outcomes.

Keywords: Hematological indicators; immune-related adverse events; immunotherapy; non-small cell lung cancer; risk factors.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
Distribution of irAEs types.
Figure 2
Figure 2
Kaplan-Meier survival analysis of OS k-m curves between. A. irae and non-irae groups. B. k-m curves for patients with different irae grades. Note: OS: Overall Survival.
Figure 3
Figure 3
Correlation analysis of patients with different severity of irAEs with hematological indicators. A. Correlation analysis between ANC and patients with different severity of irAEs. B. Correlation between LYM and patients with different severity of irAEs. C. Correlation between NLR and patients with different severity of irAEs. D. Correlation analysis between PLR and patients with different severity of irAEs. E. Correlation analysis between SII and patients with different severity of irAEs. F. Correlation analysis between AAPR and patients with different severity of irAEs. G. Correlation between AFR and patients with different severity of irAEs. Note: ANC: Absolute Neutrophil Count, LYM: Lymphocyte Count, NLR: Neutrophil to Lymphocyte Ratio, PLR: Platelet to Lymphocyte Ratio, SII: Systemic Immune-Inflammation Index, AAPR: Albumin to Alkaline Phosphatase Ratio, AFR: Albumin to Fibrinogen Ratio.
Figure 4
Figure 4
Forest plot of logistic regression analysis for each indicator. Note: ANC: Absolute Neutrophil Count, LYM: Lymphocyte Count, NLR: Neutrophil to Lymphocyte Ratio, PLR: Platelet to Lymphocyte Ratio, SII: Systemic Immune-Inflammation Index, AAPR: Albumin to Alkaline Phosphatase Ratio, AFR: Albumin to Fibrinogen Ratio.
Figure 5
Figure 5
ROC curve for predicting the occurrence of irAEs in NSCLC patients receiving ICIs treatment. Note: ANC: Absolute Neutrophil Count, LYM: Lymphocyte Count, NLR: Neutrophil to Lymphocyte Ratio, PLR: Platelet to Lymphocyte Ratio, SII: Systemic Immune-Inflammation Index, AAPR: Albumin to Alkaline Phosphatase Ratio, AFR: Albumin to Fibrinogen Ratio.
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