中性粒细胞与淋巴细胞比值在非小细胞肺癌二线免疫治疗中的预后和预测作用

International Journal of Clinical Oncology and Cancer Research Pub Date : 2021-06-28 DOI:10.11648/j.ijcocr.20210602.16

C. Bennati, M. D'Arcangelo, A. Gili, Federica Gazzaneo, S. Pini, A. Menghi, M. Montanari, G. Papiani, V. Mazza, S. Scodes, M. Spreafico, G. Rossi, D. Caruso, G. Bellezza, M. Mandarano, S. Tamberi

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引用次数: 0

摘要

背景:程序性死亡配体1 (Programmed death-ligand 1, PD-L1)在免疫组织化学中的表达是唯一被批准的非小细胞肺癌(NSCLC)免疫治疗的生物标志物，但仍不尽如人意。中性粒细胞与淋巴细胞比率(NLR)是全身性炎症的替代指标，可能与免疫治疗的结果相关。这项回顾性研究(NCT03816657)探讨了NLR在预测纳武单抗获益和对超进展(HPD)易感性中的作用。方法:173例接受纳武单抗治疗的nsclc患者的PD-L1、基线和治疗时NLR值。PD-L1阳性定义为≥1%的肿瘤细胞表达;NLR分为高(≥5)和低(<5)。患者分为4组:1组(PD-L1+/低NLR)， 2组(PD-L1-/高NLR)， 3组(PD-L1+/高NLR)， 4组(PD-L1-/低NLR)。一项具有里程碑意义的分析探讨了队列和NLR变化对客观缓解率(ORR)、无进展生存期(PFS)、总生存期(OS)及其对HPD的影响。结果:PD-L1阳性的占48%，阴性的占52%。治疗前NLR≥5的患者占42%，<5的患者占58%;在大约50%的患者中，治疗期间NLR≥5。PD-L1阳性与预后无关。高治疗前和治疗中NLR是ORR (p=0.004)、PFS (p<0.0001)和OS (p<0.0001)的负预测因子。高NLR组(2和4)的预后比低NLR组差。在纳武单抗开始后4周，相对NLR偏移≥25%与PFS和OS降低相关，而其降低或稳定性与预后改善相关。虽然NLR值及其动态不影响HPD的发生(p=0.062)，但53%的高进展者属于高NLR队列。结论:目前的回顾性分析支持高NLR作为一个独立的负面预测因素的作用。它在免疫治疗期间的增加可以识别对免疫治疗反应可能性低的患者。

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Prognostic and Predictive Role of Neutrophil to lymphocyte Ratio in Second Line Immunotherapy of Non-small Cell Lung Cancer

Background: Programmed death-ligand 1 (PD-L1) expression at immunohistochemistry is the only approved, but still unsatisfactory, biomarker for immunotherapy in Non-Small Cell Lung Cancer (NSCLC). Neutrophil to Lymphocyte ratio (NLR) is a surrogate of systemic inflammation and could correlate with outcome to immunotherapy. This retrospective study (NCT03816657) explored the role of NLR in predicting benefit to nivolumab and susceptibility to hyperprogression (HPD). Methods: PD-L1, baseline and on-therapy NLR values were available in 173NSCLC patients receiving nivolumab. PD-L1 positivity was defined as expression on ≥1% of tumor cells; NLR was dichotomized in high (≥5) or low (<5). Patients were divided in 4 cohorts: 1 (PD-L1+/low NLR), 2 (PD-L1-/high NLR), 3 (PD-L1+/high NLR), 4 (PD-L1-/low NLR). A landmark analysis explored the impact of cohorts and NLR change on objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and its influence on HPD. Results: PD-L1 was positive in 48% and negative in 52% of cases. Pre-treatment NLR was ≥5in 42% and <5 in 58%of patients; on-treatment NLR was ≥5in approximately 50% of patients. PD-L1 positivity was not associated with outcome. Both high pre- and on-therapy NLR was a negative predictor of ORR (p=0.004), PFS (p<0.0001) and OS (p<0.0001). High NLR cohorts (2 and 4) showed poorer outcome than low NLR cohorts. Relative NLR excursion ≥25% at 4 weeks from nivolumab start was associated with reduced PFS and OS, while its decrease or stability was associated with improved outcomes. Although NLR value and its dynamic did not influence HPD occurrence (p=0.062), 53% of hyperprogressors belonged to high NLR cohorts. Conclusion: The current retrospective analysis supports the role of high NLR as a independent negative predictive factor. Its increment during immunotherapy may identify patients with low likelihood of response to immunotherapy.

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International Journal of Clinical Oncology and Cancer Research

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