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帕博利珠单抗治疗的高PD-L1表达非小细胞肺癌患者外周血生物标志物与临床结局的相关性

Correlation of peripheral blood biomarkers with clinical outcomes in NSCLC patients with high PD-L1 expression treated with pembrolizumab.

作者信息

Sánchez-Gastaldo Amparo, Muñoz-Fuentes Miguel A, Molina-Pinelo Sonia, Alonso-García Miriam, Boyero Laura, Bernabé-Caro Reyes

机构信息

Medical Oncology Department, Virgen del Rocío University Hospital, Seville, Spain.

Institute of Biomedicine of Seville (IBiS) (HUVR, CSIC, University of Seville), Seville, Spain.

出版信息

Transl Lung Cancer Res. 2021 Jun;10(6):2509-2522. doi: 10.21037/tlcr-21-156.

DOI:10.21037/tlcr-21-156
PMID:34295658
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8264316/
Abstract

BACKGROUND

Immune checkpoint inhibitors (ICIs) are currently the standard therapy in advanced non-small cell lung cancer (NSCLC); however, there is no well-established prognostic biomarker. We investigated the relationship between survival outcomes and three peripheral blood biomarkers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR), as well as a new score termed the risk blood biomarker (RBB), calculated from the combination of the neutrophil-monocyte-to-lymphocyte ratio (NMLR) and white blood cell count (WBC).

METHODS

This study included patients with stage IV or recurrent NSCLC confirmed with programmed death ligand 1 (PD-L1) expression ≥50% who received pembrolizumab monotherapy as first-line treatment at the Virgen del Rocío University Hospital in Seville, Spain. To establish the relationship between baseline peripheral blood biomarkers and survival outcomes, progression free survival (PFS) and overall survival (OS), we used the Kaplan-Meier method and multivariable Cox regression models.

RESULTS

A total of 51 patients were included in this study. In multivariate analysis, baseline NLR and PLR showed a strong association with PFS [NLR hazard ratio (HR): 0.19, 95% confidence interval (CI): 0.09-0.44, P<0.001; PLR HR: 0.46, 95% CI: 0.23-0.92, P=0.03] and OS (NLR HR: 0.07, 95% CI: 0.02-0.19, P<0.001; PLR HR: 0.29, 95% CI: 0.13-0.67, P=0.004), and the MLR was associated with OS (MLR HR: 0.34, 95% CI: 0.15-0.76, P=0.01). According to the RBB score, groups with lower scores were associated with superior PFS (group 0: HR: 0.16, 95% CI: 0.06-0.41, P<0.001 and group 1: HR: 0.29, 95% CI: 0.12-0.73, P=0.01) and OS (group 0: HR: 0.04, 95% CI: 0.01-0.17, P<0.001 and group 1: HR: 0.15, 95% CI: 0.05-0.42, P<0.001).

CONCLUSIONS

Low baseline NLR, MLR and PLR are significantly associated with better PFS, and low baseline NLR and PLR are associated with better OS. Additionally, we identified three subgroups of patients using the RBB score, and low scores were associated with improved survival outcomes and response to therapy.

摘要

背景

免疫检查点抑制剂(ICI)目前是晚期非小细胞肺癌(NSCLC)的标准治疗方法;然而,尚无成熟的预后生物标志物。我们研究了生存结局与三种外周血生物标志物之间的关系,这三种生物标志物包括中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)和单核细胞与淋巴细胞比值(MLR),以及一种新的评分,即风险血液生物标志物(RBB),它由中性粒细胞-单核细胞与淋巴细胞比值(NMLR)和白细胞计数(WBC)组合计算得出。

方法

本研究纳入了西班牙塞维利亚维根德洛克大学医院确诊为程序性死亡配体1(PD-L1)表达≥50%的IV期或复发性NSCLC患者,这些患者接受帕博利珠单抗单药作为一线治疗。为了确定基线外周血生物标志物与生存结局、无进展生存期(PFS)和总生存期(OS)之间的关系,我们使用了Kaplan-Meier方法和多变量Cox回归模型。

结果

本研究共纳入51例患者。在多变量分析中,基线NLR和PLR与PFS [NLR风险比(HR):0.19,95%置信区间(CI):0.09 - 0.44,P < 0.001;PLR HR:0.46,95% CI:0.23 - 0.92,P = 0.03]和OS(NLR HR:0.07,95% CI:0.02 - 0.19,P < 0.001;PLR HR:0.29,95% CI:0.13 - 0.67,P = 0.004)密切相关,MLR与OS相关(MLR HR:0.34,95% CI:0.15 - 0.76,P = 0.01)。根据RBB评分,得分较低的组与较好的PFS(0组:HR:0.16,95% CI:0.06 - 0.41,P < 0.001;1组:HR:0.29,95% CI:0.12 - 0.73,P = 0.01)和OS(0组:HR:0.04,95% CI:0.01 - 0.17,P < 0.001;1组:HR:0.15,95% CI:0.05 - 0.42,P < 0.001)相关。

结论

低基线NLR、MLR和PLR与更好的PFS显著相关,低基线NLR和PLR与更好的OS相关。此外,我们使用RBB评分确定了三组患者,得分较低与生存结局改善和治疗反应相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e27/8264316/183a0a57d234/tlcr-10-06-2509-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e27/8264316/58c7c23e2f85/tlcr-10-06-2509-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e27/8264316/1407b962bc84/tlcr-10-06-2509-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e27/8264316/a25098b91694/tlcr-10-06-2509-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e27/8264316/183a0a57d234/tlcr-10-06-2509-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e27/8264316/58c7c23e2f85/tlcr-10-06-2509-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e27/8264316/1407b962bc84/tlcr-10-06-2509-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e27/8264316/a25098b91694/tlcr-10-06-2509-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e27/8264316/183a0a57d234/tlcr-10-06-2509-f4.jpg

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