Neutrophil-to-lymphocyte ratio evolution is an independent predictor of early progression of second-line nivolumab-treated patients with advanced non-small-cell lung cancers

INTRODUCTION: Although second-line immunotherapy obtained better outcomes than chemotherapy for patients with advanced non-small–cell lung cancers (NSCLCs), it is expensive and only a minority of patients seem to benefit, based on early tumor progression post-immunotherapy. Notable host inflammation, characterized by biomarkers (e.g. neutrophil-to-lymphocyte ratio (NLR])), prolongs overall survival (OS) of surgery-, chemotherapy- and immunotherapy-treated patients. To our knowledge, no previous studies used biomarker evolution to analyze the immunotherapy impact on host inflammation. Immunotherapy mainly exerts its activity by lymphocyte reactivation. METHODS: This retrospective study was conducted on patients, selected by their progression status just before their 4(th) nivolumab injection, and treated at Bordeaux and Limoges University Hospitals. A comparative group of at least 1-year responders was also selected. Clinical parameters and hematological data just before the 1(st) (baseline) and 4(th) nivolumab infusions were collected to calculate the NLR change (ΔNLR) between those two infusions. The combined impact of the different known prognostic factors was also analyzed with multivariable analyses. RESULTS: Fifty-nine patients were included. The 29 early progressors had significantly more frequent ΔNLR > 1 (p = 0.0007), OR 18.08 [95% CI 2.96–246.24] with progressive disease as best response to prior treatment line (p = 0.0014). ΔNLR < 1 prolonged OS (HR 0.001 [0.0007–0.18], p = 0.001); as did a partial response to prior line of systemic treatment (HR 0.14 [0.03––0.56], p = 0.005). CONCLUSION: Based on selected early progressors given second-line immunotherapy for advanced NSCLC, progression as best response to prior treatment and ΔNLR > 1 characterized the early progressors and shortened OS after starting nivolumab. This phenomenon questions nivolumab utility in patients with a major host neutrophil inflammation.