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

BMC Cancer

Philip C. Mack¹  Fred R. Hirsch¹  Scott Newman²  Kristin L. Ayers²  Kyeryoung Lee²  Gaspard Debussche²  David Corrigan²  Meng Ma²  Jonathan McCafferty²  Xiang Zhou²  Eric E. Schadt³  Shuyu D. Li³  Rong Chen³  Jane J. Liu⁴ 

[1] Center of Thoracic Oncology/Tisch Cancer Institute and Icahn School of Medicine, Mount Sinai, 1 Gustave L. Levy Pl, 10029, New York, NY, USA;Sema4, a Mount Sinai Venture, 333 Ludlow Street, 06902, Stamford, CT, USA;Sema4, a Mount Sinai Venture, 333 Ludlow Street, 06902, Stamford, CT, USA;Center of Thoracic Oncology/Tisch Cancer Institute and Icahn School of Medicine, Mount Sinai, 1 Gustave L. Levy Pl, 10029, New York, NY, USA;Sema4, a Mount Sinai Venture, 333 Ludlow Street, 06902, Stamford, CT, USA;Illinois Cancer Care, 8940 N Wood Sage Rd, 61615, Peoria, IL, USA;

关键词: Non-small cell lung cancer;    Immune checkpoint inhibitor;    Neutrophil-lymphocyte ratio;    Anemia;    Biomarker;   

DOI  :  10.1186/s12885-021-08194-9

来源: Springer

【 摘 要 】

BackgroundImmune 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.MethodsWe 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.ResultsOf 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).ConclusionsWe 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.

【 授权许可】

CC BY