Lin Xinqing, Deng Haiyi, Yang Yilin, Wu Jianhui, Qiu Guihuan, Li Suyang, Xie Xiaohong, Liu Ming, Xie Zhanhong, Qin Yinyin, Song Yong, Zhou Chengzhi
State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing, China.
Front Oncol. 2021 Jul 13;11:698832. doi: 10.3389/fonc.2021.698832. eCollection 2021.
Checkpoint inhibitor-related pneumonitis (CIP) is a potentially fatal immune-related adverse event that occurs during treatment with immune checkpoint inhibitors (ICIs). However, the roles played by peripheral blood parameters in CIP development remain unclear. Here, we aimed to identify which blood biomarkers correlated with the development and prognosis of CIP in patients with lung cancer.
We conducted a retrospective analysis of 87 patients with CIP (CIP group) and 87 patients without CIP (control group). Cytokines, blood routine, lactate dehydrogenase (LDH) and albumin (ALB) were collected at baseline (before ICIs), at onset of pneumonitis (in the CIP group), and before the last dose of ICI (in the control group). We compared the baseline values and changes over time in various blood parameters between the CIP and control groups. The CIP outcomes were collected and compared according to the median values of these parameters.
Squamous carcinoma (odds ratio [OR]: 3.02; = 0.004) and ICI monotherapy (OR: 6.56; = 0.004) correlated with a high risk of CIP. In the CIP group, interleukin (IL)-6 and platelet-to-lymphocyte ratio (PLR) at CIP were significantly increased relative to baseline. By contrast, IL-6 and PLR reduced over time in the control group. Significant decrease in absolute lymphocyte count (ALC) and increases in IL-10, neutrophil to lymphocyte ratio (NLR), and LDH levels were observed from baseline to CIP. No significant change in these parameters was observed in the control group relative to baseline. ALB decreased in both groups, but the decrease in the CIP group was greater (9.21% . 2.44%; = 0.020). High IL-6 levels (OR: 5.23, 95% confidence interval [CI]: 1.15-23.86; = 0.033), and low levels of ALB (OR: 0.16, 95% CI: 0.04-0.64; = 0.009) measured at the time of CIP symptom onset were associated with severe pneumonitis. Low concentration of IL-6 (hazard ratio [HR]: 0.17, 95% CI: 0.03-0.95; = 0.044) and high ALB levels (HR: 0.28, 95% CI: 0.08-0.94; = 0.040) were correlated with favorable overall survival in CIP.
Increase in IL-6, IL-10, NLR, PLR, and LDH levels or reduced ALC and ALB levels were associated with the occurrence of CIP in lung cancer patients. High IL-6 and low ALB levels at onset of CIP were related to severe grade and poor prognosis of CIP.
检查点抑制剂相关肺炎（CIP）是免疫检查点抑制剂（ICI）治疗期间发生的一种潜在致命的免疫相关不良事件。然而，外周血参数在CIP发生中的作用仍不清楚。在此，我们旨在确定哪些血液生物标志物与肺癌患者CIP的发生和预后相关。
我们对87例CIP患者（CIP组）和87例无CIP患者（对照组）进行了回顾性分析。在基线（ICI治疗前）、肺炎发作时（CIP组）和最后一剂ICI前（对照组）收集细胞因子、血常规、乳酸脱氢酶（LDH）和白蛋白（ALB）。我们比较了CIP组和对照组之间各种血液参数的基线值和随时间的变化。根据这些参数的中位数收集并比较CIP结果。
鳞状细胞癌（比值比[OR]：3.02；P = 0.004）和ICI单药治疗（OR：6.56；P = 0.004）与CIP高风险相关。在CIP组中，CIP时白细胞介素（IL）-6和血小板与淋巴细胞比值（PLR）相对于基线显著升高。相比之下，对照组中IL-6和PLR随时间降低。从基线到CIP观察到绝对淋巴细胞计数（ALC）显著降低，IL-10、中性粒细胞与淋巴细胞比值（NLR）和LDH水平升高。对照组相对于基线在这些参数上未观察到显著变化。两组中ALB均降低，但CIP组降低幅度更大（9.21% 对 2.44%；P = 0.020）。CIP症状发作时测得的高IL-6水平（OR：5.23，95%置信区间[CI]：1.15 - 23.86；P = 0.033）和低ALB水平（OR：0.16，95% CI：0.04 - 0.64；P = 0.009）与严重肺炎相关。低浓度IL-6（风险比[HR]：0.17，95% CI：0.03 - 0.95；P = 0.044）和高ALB水平（HR：0.28，95% CI：0.08 - 0.94；P = 0.040）与CIP患者的良好总生存相关。
IL-6、IL-10、NLR、PLR和LDH水平升高或ALC和ALB水平降低与肺癌患者CIP的发生相关。CIP发作时高IL-6和低ALB水平与CIP的严重程度和不良预后相关。
