Service de Pneumologie, CHU, Limoges, France.
Service d'Oncologie Médicale, CHU, Limoges, France.
PLoS One. 2019 Jul 17;14(7):e0219060. doi: 10.1371/journal.pone.0219060. eCollection 2019.
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.
This retrospective study was conducted on patients, selected by their progression status just before their 4th 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 1st (baseline) and 4th 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.
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).
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.
尽管二线免疫疗法在晚期非小细胞肺癌（NSCLC）患者中的疗效优于化疗，但根据免疫治疗后早期肿瘤进展情况，只有少数患者似乎从中受益，因为其费用昂贵。显著的宿主炎症，其特征是生物标志物（例如中性粒细胞与淋巴细胞比值（NLR）），可延长手术、化疗和免疫治疗患者的总生存期（OS）。据我们所知，以前没有研究使用生物标志物的变化来分析免疫疗法对宿主炎症的影响。免疫疗法主要通过淋巴细胞的再激活发挥作用。
这项回顾性研究在波尔多和里摩日大学医院选择了进展期患者（根据他们第 4 次纳武利尤单抗注射前的进展情况选择），并对他们进行了治疗。还选择了至少有 1 年反应的对照组。收集了两次纳武利尤单抗输注前的临床参数和血液学数据，以计算两次输注之间的 NLR 变化（ΔNLR）。还通过多变量分析来分析不同已知预后因素的综合影响。
共纳入 59 例患者。29 例早期进展者的ΔNLR > 1 更为频繁（p = 0.0007），最佳疗效为疾病进展的患者的 OR 为 18.08 [95%CI 2.96-246.24]，与前一线治疗相比（p = 0.0014）。ΔNLR < 1 延长了 OS（HR 0.001 [0.0007-0.18]，p = 0.001）；前一线系统治疗的部分反应也是如此（HR 0.14 [0.03--0.56]，p = 0.005）。
基于选择的晚期 NSCLC 二线免疫治疗的早期进展者，最佳疗效为疾病进展和ΔNLR > 1 特征的早期进展者，以及开始纳武利尤单抗后 OS 缩短。这一现象对在宿主中性粒细胞炎症较大的患者中使用纳武利尤单抗提出了质疑。
