Eosinophil and IFN-γ associated with immune-related adverse events as prognostic markers in patients with non-small cell lung cancer treated with immunotherapy

Objectives: Immune checkpoint inhibitors (ICIs) alone or combined with other antitumor agents are largely used in lung cancer patients, which show both positive effects and side effects in particular subjects. Our study aims to identify biomarkers that can predict response to immunotherapy or risk of side effects, which may help us play a positive role and minimize the risk of adverse effects in clinical practice.

Methods: We retrospectively collected data from patients with advanced non-small cell lung cancer (NSCLC) treated with ICIs at our center. Patients who received initial ICI therapy for >1 year without progression of disease were classified as long-term treatment (LT) group, while others were classified as the non-long-term treatment (NLT) group. Multivariate logistic analysis was performed to identify independent risk factors of progression-free survival (PFS) and immune-related adverse events (irAEs).

Results: A total of 83 patients (55.7%) had irAEs. The median PFS for patients in grades 1-2 of irAEs vs. grades 3-4 vs non-irAEs groups was (undefined vs. 12 vs. 8 months; p = 0.0025). The 1-year PFS rate for multisystem vs. single vs. non-irAE groups was 63%, 56%, and 31%, respectively. Signal transduction of inflammatory cytokines improves clinical prognosis through immunomodulatory function, but the benefit is also limited by the resulting organ damage, making it a complex immune balance. Serum biomarkers including EOS% of ≥ 1.15 (HR: 8.30 (95% CI, 2.06 to 33.42); p = 0.003) and IFN-γ of ≥ 3.75 (HR: 5.10 (95% CI, 1.29 to 20.15), p = 0.02) were found to be predictive for irAEs.

Conclusion: EOS% of ≥1.15% and IFN-γ of ≥3.75 ng/L were considered peripheral-blood markers for irAEs and associated with improved clinical outcomes for immunotherapy in patients with advanced NSCLC.