Early neutrophil-to-lymphocyte ratio changes may act as predictors of response to immune checkpoint inhibitors in non-small-cell lung cancer

Background: Treatment with immune checkpoint inhibitors (ICIs) does not benefit all patients with advanced non-small-cell lung cancer (NSCLC). The early identification of resistance may decrease the risk of hyperprogression, adverse events, and costs. Materials and methods: Serum levels of absolute lymphocyte count (ALC), absolute neutrophil count (ANC), neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH) and C-reactive protein (CRP) were retrospectively analyzed in thirty-five patients treated with an ICI in first line and forty-four patients in second line. These parameters were correlated with objective response rate (ORR) at first evaluation, progression-free survival (PFS) and overall survival (OS). Results: The median follow-up time was 20 months (range 4.2–37.6). In the patient group treated with ICIs in first line, NLR at 6 weeks was higher in non-responders (p = 0.017) and was associated with shorter PFS (HR 1.17; p = 0.017) and OS (HR 1.32; p = 0.0008). An NLR at 6 weeks of more than 3.3 was identified as the optimal cut-point value. Baseline LDH was only associated with OS (HR 1.03; p = 0.04). In the second line group, CRP at 3 weeks was associated with PFS (HR 1.02; p = 0.01) and OS (HR 1.02; p = 0.01) but not with tumor response while early NLR changes were associated with all three factors. Conclusions: No baseline predictive biomarkers for response to ICIs could be identified. Early NLR changes could allow for the rapid identification of non-responders and were associated with shorter PFS and OS in patients receiving ICIs in first and second line.