ROC Analysis Identifies Baseline and Dynamic NLR and dNLR Cut-Offs to Predict ICI Outcome in 402 Advanced NSCLC Patients

Abstract

Background: Neutrophil-to-Lymphocyte Ratio (NLR) and derived Neutrophils-to-(Leukocytes minus neutrophils) Ratio (dNLR) have been proposed as possible biomarkers of response to immune checkpoint inhibitors (ICI). However, in non-small cell lung cancer (NSCLC) studies, various NLR and/or dNLR cut-offs have been used, manly based on previous reports on melanoma. Methods: In this Italian multicenter retrospective study, NLR, dNLR, platelet-to-lymphocyte ratio, albumin, and lactate dehydrogenase (LDH) were longitudinally assessed in patients with stage IV non-small cell lung cancer (NSCLC) treated with ICI. The primary objective was to evaluate if baseline parameters predicted response to ICI, using Receiver Operating Characteristic (ROC) curves. Secondary endpoint was to evaluate if dynamic changing of NLR and dNLR also predicted response. Results: Data of 402 patients were collected and analyzed. Among the baseline parameters considered, NLR and dNLR were the most appropriate biomarkers according to the ROC analyses, which also identified meaningful cut-offs (NLR = 2.46; dNLR = 1.61). Patients with low ratios reported a significantly improved outcome, in terms of overall survival (p = 0.0003 for NLR; p = 0.0002 for dNLR) and progression free survival (p = 0.0004 for NLR; p = 0.005 for dNLR). The role of NLR and dNLR as independent biomarkers of response was confirmed in the Cox regression model. When assessing NLR and dNLR dynamics from baseline to cycle 3, a decrease ≥1.04 for NLR and ≥0.41 for dNLR also predicted response. Conclusions in our cohort, we confirmed that NLR and dNLR, easily assessable on peripheral blood, can predict response at baseline and early after ICI initiation. For both baseline and dynamic assessment, we identified clinically meaningful cut-offs, using ROC curves.

The Palliative Prognostic (PaP) Score without Clinical Evaluation Predicts Early Mortality among Advanced NSCLC Patients Treated with Immunotherapy

“…Interestingly, the LIPI score failed to demonstrate a prognostic value among ECOG PS ≥ 2 patients, in terms of OS ( p = 0.91), within a small subgroup analysis (51/466 patients) [ 5 ]. Analogously, LDH, NLR, and dNLR were demonstrated to be predictive biomarkers of survival with moderate accuracy at one year (AUC 0.60, 0.67, and 0.67, respectively) by another retrospective study [ 20 ]. These data may indicate that clinical conditions expressed as PS or laboratory test-only scores may not be enough to predict the short-term survival probability.…”

NSCLC Biomarkers to Predict Response to Immunotherapy with Checkpoint Inhibitors (ICI): From the Cells to In Vivo Images

“…The negative prognostic and predictive role of circulating neutrophils and of the neutrophil/lymphocyte ratio in particular after ICIs, has been addressed in numerous retrospective studies, reporting a significant association. While the neutrophil/lymphocyte ratio or derived neutrophil/lymphocyte ratio are easy to assess from routine blood cell count and are reproducible, a clinically meaningful threshold is awaited upon for prospective validation [ 103 , 104 ].…”

NSCLC Biomarkers to Predict Response to Immunotherapy with Checkpoint Inhibitors (ICI): From the Cells to in-Vivo Images

“…The negative prognostic and predictive role of circulating neutrophils, and in particular of neutrophil/lymphocyte ratio, after ICIs, has been addressed in numerous retrospective studies, reporting a significant association. Whether neutrophil/lymphocyte ratio or derived neutrophil/lymphocyte ratio are easy to assess from routine blood cell count and reproducible, a clinically meaningful threshold is awaited for prospective validation [93,94].…”