Association of the Lung Immune Prognostic Index With Immune Checkpoint Inhibitor Outcomes in Patients With Advanced Non-Small Cell Lung Cancer
Association of the Lung Immune Prognostic Index With Immune Checkpoint Inhibitor Outcomes in Patients With Advanced Non-Small Cell Lung Cancer
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DOI：
10.1001/jamaoncol.2017.4771
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发表时间：
2018-03-01
期刊：
影响因子：
28.4
通讯作者：
Besse, Benjamin
中科院分区：
文献类型：
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作者：
Mezquita, Laura;Auclin, Edouard;Besse, Benjamin
重要性 衍生性中性粒细胞/（白细胞减去中性粒细胞）比率 (dNLR) 和乳酸脱氢酶 (LDH) 水平与黑色素瘤患者的免疫检查点抑制剂 (ICI) 结局相关。 目的 确定治疗前 dNLR 和 LDH 是否与晚期非小细胞肺癌患者对 ICI 的耐药性相关 (NSCLC)。 设计、背景和参与者 多中心回顾性研究，其中包括在 8 个欧洲中心接受程序性死亡 1/程序性死亡配体 1 (PD-1/PD-L1) 抑制剂治疗的测试 (n = 161) 和验证集 (n = 305)，以及仅接受化疗的对照队列 (n = 162)。在 ICI 治疗前测量全血细胞计数、LDH 和白蛋白水平。制定了基于 dNLR 大于 3 和 LDH 大于正常上限 (ULN) 的肺免疫预后指数 (LIPI)，描述了 3 组（良好，0 个因素；中等，1 个因素；差，2 个因素）。 主要结果和措施 主要终点是总生存期 (OS)。次要终点是无进展生存期 (PFS) 和疾病控制率 (DCR)。 结果 在 ICI 合并队列 (N = 466) 中，301 名患者 (65%) 为男性，422 名 (90%) 为当前或既往吸烟者，401 名 (87%) 的体能状态为 1 或更低；诊断时的中位年龄为 62 岁（范围为 29-86 岁）； 270 人（58%）患有腺癌，159 人（34%）患有鳞状组织学亚型。在 129 名有 PD-L1 数据的患者中，通过免疫组织化学分析，96 名（74%）的 PD-L1 至少为 1%，33 名（26%）结果为阴性。在测试队列中，中位 PFS 和 OS 分别为 3 (95% CI, 2-4) 和 10 (95% CI, 8-13) 个月。 dNLR 大于 3 和 LDH 大于 ULN 与 OS 独立相关（风险比 [HR] 2.22；95% CI，1.23-4.01；HR，2.51；95% CI，1.32-4.76）。差、中等和良好 LIPI 的中位 OS 分别为 3 个月（95% CI，1 个月未达到 [NR]）、10 个月（95% CI，8 个月至 NR）和 34 个月（95% CI，17 个月至 NR），中位 PFS 分别为 2.0（95% CI，1.7-4.0）、3.7（95% CI， 3.0-4.8）和6.3 (95% CI, 5.0-8.0) 个月（均 P
IMPORTANCE Derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and lactate dehydrogenase (LDH) level have been correlated with immune checkpoint inhibitor (ICI) outcomes in patients with melanoma.OBJECTIVE To determine whether pretreatment dNLR and LDH are associated with resistance to ICIs in patients with advanced non-small cell lung cancer (NSCLC).DESIGN, SETTING, AND PARTICIPANTS Multicenter retrospective study with a test (n = 161) and a validation set (n = 305) treated with programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors in 8 European centers, and a control cohort (n = 162) treated with chemotherapy only. Complete blood cell counts, LDH, and albumin levels were measured before ICI treatment. A lung immune prognostic index (LIPI) based on dNLR greater than 3 and LDH greater than upper limit of normal (ULN) was developed, characterizing 3 groups (good, 0 factors; intermediate, 1 factor; poor, 2 factors).MAIN OUTCOMES AND MEASURES The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS) and disease control rate (DCR).RESULTS In the pooled ICI cohort (N = 466), 301 patients (65%) were male, 422 (90%) were current or former smokers, and 401 (87%) had performance status of 1 or less; median age at diagnosis was 62 (range, 29-86) years; 270 (58%) had adenocarcinoma and 159 (34%) had squamous histologic subtype. Among 129 patients with PD-L1 data, 96 (74%) had PD-L1 of at least 1% by immunohistochemical analysis, and 33 (26%) had negative results. In the test cohort, median PFS and OS were 3 (95% CI, 2-4) and 10 (95% CI, 8-13) months, respectively. A dNLR greater than 3 and LDH greater than ULN were independently associated with OS (hazard ratio [HR] 2.22; 95% CI, 1.23-4.01 and HR, 2.51; 95% CI, 1.32-4.76, respectively). Median OS for poor, intermediate, and good LIPI was 3 months (95% CI, 1 month to not reached [NR]), 10 months (95% CI, 8 months to NR), and 34 months (95% CI, 17 months to NR), respectively, and median PFS was 2.0 (95% CI, 1.7-4.0), 3.7 (95% CI, 3.0-4.8), and 6.3 (95% CI, 5.0-8.0) months (both P