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

Abstract

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.

<p>Low Prognostic Nutritional Index Predicts Poor Clinical Outcomes in Patients with Stage IIIB Non-small-cell Lung Carcinoma Undergoing Chemoradiotherapy</p>

“…42 To our best information, to date, no study particularly addressed the prognostic significance of PNI in NSCLC patients treated with the standard CRT followed by durvalumab or other immunotherapeutics. Nevertheless, neutrophil to lymphocyte ratio which is another inflammation index has been addressed as a prognostic indicator in some limited studies, [43][44][45] and a meta-analysis. 46 Reputably, Jiang et al conducted a comprehensive meta-analysis literature search to assess the relationship between pretreatment neutrophil to lymphocyte ratio and OS or PFS in advanced-stage cancer patients treated with immunotherapy.The pooled results of this meta-analysis of 27 studies with 4647 patients unveiled that high pretreatment neutrophil to lymphocyte ratio was closely linked with significantly shorter OS (HR = 1.98; P < 0.001) and PFS (HR = 1.78; P < 0.001).…”

Nivolumab for Previously Treated Patients with Non-Small-Cell Lung Cancer—Daily Practice versus Clinical Trials

“…A high LIPI value was indicated as an independent negative prognostic factor (HR 3.67, 95% CI 1.96–6.86; p < 0.0001) [ 33 ]. Several other inflammatory-related markers, such as the neutrophil to lymphocyte ratio (NLR), dNLR, LDH, interleukin 8, and indoleamine 2,3 dioxygenase activity were also found to be important [ 35 , 36 ].…”

Pretreatment Neutrophil-to-Lymphocyte Ratio (NLR) May Predict the Outcomes of Advanced Non-small-cell Lung Cancer (NSCLC) Patients Treated With Immune Checkpoint Inhibitors (ICIs)

“…We summarized the characteristics in Table 1. Of all included studies, five were performed in the United States (7,31,33,34,40), four in Japan (32,36,39,44), and the remaining eight studies were conducted in Switzerland (35), Canada (37), France (38,45), Bulgaria (41), China (42), Germany (43), and Italy (46), respectively. In terms of the ICIs used, 11 studies reported on nivolumab (7, 31-36, 39, 42, 45, 46), 2 studies reported on pembrolizumab (41,44), and the remaining 4 studies did not specify the type of ICIs (37,38,40,43).…”