Journal Article

A composite biomarker of neutrophil-lymphocyte ratio and hemoglobin level correlates with clinical response to PD-1 and PD-L1 inhibitors in advanced non-small cell lung cancers

McCafferty, Jonathan, Newman, Scott, Corrigan, David, Ayers, Kristin L., Zhou, Xiang, Ma, Meng, Hirsch, Fred R., Lee, Kyeryoung, Chen, Rong, Schadt, Eric E., Li, Shuyu D., Liu, Jane J., Debussche, Gaspard, Mack, Philip C.

2021

Overview

Background Immune checkpoint inhibitors (ICIs) have been incorporated into various clinical oncology guidelines for systemic treatment of advanced non-small cell lung cancers (aNSCLC). However, less than 50% (and 20%) of the patients responded to the therapy as a first (or second) line of therapy. PD-L1 immunohistochemistry (IHC) is an extensively studied biomarker of response to ICI, but results from this test have equivocal predictive power. In order to identify other biomarkers that support clinical decision-making around whether to treat with ICIs or not, we performed a retrospective study of patients with aNSCLC who underwent ICI-based therapy in the Mount Sinai Health System between 2014 and 2019. Methods We analyzed data from standard laboratory tests performed in patients as a part of the routine clinical workup during treatment, including complete blood counts (CBC) and a comprehensive metabolic panel (CMP), to correlate test results with clinical response and survival. Results Of 11,138 NSCLC patients identified, 249 had been treated with ICIs. We found associations between high neutrophil-to-lymphocyte ratio (NLR ≥ 5) and poor survival in ICI-treated NSCLC. We further observed that sustained high NLR after initiation of treatment had a more profound impact on survival than baseline NLR, regardless of PD-L1 status. Hazard ratios when comparing patients with NLR ≥ 5 vs. NLR < 5 are 1.7 ( p  = 0.02), 3.4 ( p  = 4.2 × 10 − 8 ), and 3.9 ( p  = 1.4 × 10 − 6 ) at baseline, 2–8 weeks, and 8–14 weeks after treatment start, respectively. Mild anemia, defined as hemoglobin (HGB) less than 12 g/dL was correlated with survival independently of NLR. Finally, we developed a composite NLR and HGB biomarker. Patients with pretreatment NLR ≥ 5 and HGB < 12 g/dL had a median overall survival (OS) of 8.0 months (95% CI 4.5–11.5) compared to the rest of the cohort with a median OS not reached (95% CI 15.9-NE, p  = 1.8 × 10 − 5 ), and a hazard ratio of 2.6 (95% CI 1.7–4.1, p  = 3.5 × 10 − 5 ). Conclusions We developed a novel composite biomarker for ICI-based therapy in NSCLC based on routine CBC tests, which may provide meaningful clinical utility to guide treatment decision. The results suggest that treatment of anemia to elevate HGB before initiation of ICI therapy may improve patient outcomes or the use of alternative non-chemotherapy containing regimens.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Anemia / Antineoplastic Agents, Immunological - administration & dosage / Antineoplastic Agents, Immunological - adverse effects / Antineoplastic Agents, Immunological - therapeutic use / B7-H1 Antigen - antagonists & inhibitors / Biological markers / Biomarker / Biomarkers / Biomarkers, Tumor / Biomedical and Life Sciences / Biomedicine / Blood / Cancer Research / Cancer therapies / Carcinoma, Non-Small-Cell Lung - blood / Carcinoma, Non-Small-Cell Lung - drug therapy / Carcinoma, Non-Small-Cell Lung - etiology / Carcinoma, Non-Small-Cell Lung - pathology / Chemotherapy / Clinical outcomes / Decision making / Development and progression / Drug therapy / Electronic health records / Enzyme inhibitors / Erythrocyte Indices / Female / Health aspects / Health Promotion and Disease Prevention / Hemoglobin / Humans / Identification and classification / Immune checkpoint inhibitor / Immune checkpoint inhibitors / Immunohistochemistry / Immunotherapy / Kaplan-Meier Estimate / Laboratories / Leukocyte Count / Leukocytes (neutrophilic) / Lung cancer / Lung cancer, Non-small cell / Lung Neoplasms - blood / Lung Neoplasms - drug therapy / Lung Neoplasms - etiology / Lung Neoplasms - pathology / Lymphocytes / Male / Medical prognosis / Medical records / Medicine/Public Health / Mutation / Neoplasm Metastasis / Neoplasm Staging / Neutrophil-lymphocyte ratio / Neutrophils / Non-small cell lung cancer / Non-small cell lung carcinoma / Odds Ratio / Oncology / Patient outcomes / Patients / PD-1 protein / PD-L1 protein / Prognosis / Programmed Cell Death 1 Receptor - antagonists & inhibitors / Surgical Oncology / Treatment Outcome