Predictive value of peripheral blood eosinophil levels and dynamics for efficacy and safety of immune checkpoint inhibitors in non-small cell lung cancer: a real-world study

Heterogeneous benefits from immunotherapy in advanced driver gene–negative non-small cell lung cancer (NSCLC) underscore the need for biomarkers predicting efficacy and immune-related adverse event (irAE) risk. Eosinophils, routinely measured in peripheral blood and involved in antitumor immunity, may serve as practical biomarkers for predicting the efficacy and safety of immune checkpoint inhibitors (ICIs). This retrospective study enrolled 316 consecutive patients with unresectable stage III–IV NSCLC treated with ICI-based regimens at Harbin Medical University Cancer Hospital (2016–2024). Peripheral absolute eosinophil count (AEC) and eosinophil percent (E%) were measured at baseline and after cycles 2 and 4. Overall survival (OS) and progression-free survival (PFS) were the primary and secondary endpoints. Associations with irAEs were also evaluated. Multivariable Cox analysis showed that increases in AEC and E% from baseline to cycle 4 (ΔAEC and ΔE%) were independently associated with OS (ΔAEC: aHR=0.88 per doubling, p=0.036; ΔE%: aHR=0.84 per doubling, p=0.006). Optimal cut-offs for cycle 4 AEC (0.22×10 9 /L), E% (2.60%), ΔAEC (0.01×10 9 /L), and ΔE% (0.85%), determined by the minimum p-value method, indicated that values above these thresholds were significantly associated with improved OS and PFS (p<0.05). Regarding safety, 38.4% of patients developed irAEs. Higher AEC levels at cycles 2 and 4, as well as early increases from baseline to cycle 2, were associated with an elevated risk of irAEs, while baseline AEC/E% showed no significant association with irAEs. This study supports the use of peripheral blood eosinophil-related indices as prognostic and safety biomarkers in NSCLC patients treated with ICIs.