免疫检查点抑制剂联合抗血管生成药物治疗经治的晚期非小细胞肺癌临床疗效及对淋巴细胞亚群水平的影响  

Clinical Effect of Immune Checkpoint Inhibitors Combined with Anti-angiogenic Drugs on the Level of Lymphocyte Subsets in Treated Advanced Non-small Cell Lung Cancer

作　　者：李亚茹 韩亚光 李亚贝 高振林 梁欢 LI Yaru;HAN Yaguang;LI Yabei;GAO Zhenlin;LIANG Huan(Oncology Department,Shijiazhuang People's Hospital,Shijiazhuang 0500003,China;Department of Neurosurgery,Shijiazhuang People's Hospital,Shijiazhuang 0500003,China)

机构地区：[1]石家庄市人民医院肿瘤内科,河北石家庄050000 [2]石家庄市人民医院神经外科,河北石家庄050000

出　　处：《药物生物技术》2025年第1期80-86,共7页Pharmaceutical Biotechnology

基　　金：石家庄市科学技术研究与发展自筹计划项目(No.221460503)。

摘　　要：探讨免疫检查点抑制剂联合抗血管生成药物治疗经治的驱动基因阴性的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者临床疗效,同时比较治疗前后T淋巴细胞亚群水平、探讨血清CD137浓度变化。选取石家庄市人民医院肿瘤内科2020年01月至2023年02月期间收治的65例局晚期或晚期驱动基因阴性的NSCLC患者,给予安罗替尼联合信迪利单抗治疗,评价临床疗效及安全性,比较治疗前后T淋巴细胞亚群(CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+))水平,分析血清中CD137的浓度变化。患者中位PFS为6.8个月(95%CI 4.14~10.05个月),ORR为9.2%,DCR为72.3%。单因素分析结果显示,肝转移、ECOG评分与PFS有关,差异有统计学意义(P<0.05)。治疗后外周血CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平较治疗前呈逐渐升高趋势(P<0.05)。生物标志物分析显示:治疗后血清CD137浓度高于治疗前患者(中位数53.79 vs 73.03 pg/mL,P<0.05),临床获益的患者血清CD137浓度高于无临床获益的患者(中位数,68.80 vs 56.23 pg/mL,P=0.035)。不良反应的总发生率为60%(39/65),大多数不良反应为1~2级,常见不良反应为高血压、甲状腺功能减退、乏力等。免疫检查点抑制剂联合抗血管生成药物治疗经治的驱动基因阴性的晚期NSCLC具有较好的疗效、耐受性,尤其是CD137浓度高、体力营养状况良好及无肝转移患者更获益,免疫联合抗血管治疗可改善患者免疫状态。This paper aims to investigate the clinical efficacy of immune checkpoint inhibitors combined with anti-angiogenic drugs in the treatment of patients with advanced non-small cell lung cancer NSCLC,to compare the levels of T lymphocyte subsets before and after treatment,and to explore the changes in serum CD137 concentration.A total of 65 patients with advanced NSCLC or advanced driver negative NSCLC treated in the Department of Oncology of Shijiazhuang People's Hospital from January 2020 to February 2023 were selected and given anlotinib combined with sintilimab to evaluate the clinical efficacy and safety of the patients.The levels of T lymphocyte subsets(CD3^(+),CD4^(+),CD4^(+)/CD8^(+))before and after treatment were compared,and the levels of CD137 in serum were analyzed.The median PFS was 6.8 months(95%CI 4.14~10.05 months),ORR was 9.2%,and DCR was 72.3%.The results of univariate analysis showed that liver metastasis and ECOG score were related to PFS,and the difference was statistically significant(P<0.05).After treatment,the levels of CD3^(+),CD4^(+)and CD4^(+)/CD8^(+)in peripheral blood were gradually increased compared with those before treatment(P<0.05).Biomarker analysis revealed:The serum CD137 concentration after treatment was higher than that before treatment(median 53.79 pg/mL vs 73.03 pg/mL,P<0.05),and the serum CD137 concentration in patients with clinical benefit was higher than that in patients without clinical benefit(median,68.80 pg/mL vs 56.23 pg/mL,P=0.035).The overall incidence of adverse reactions was 60%(39/65),most of the adverse reactions were grade 1 to 2,and the common adverse reactions were hypertension,hypothyroidism,fatigue,etc.Immune checkpoint inhibitors combined with anti-angiogenic drugs are effective and well tolerated in the treatment of advanced NSCLC with driver negative genes.In particular,patients with high CD137 concentration,good physical nutrition and no liver metastasis were more beneficial.Immunotherapy combined with anti-angiogenic therapy can improve the immune sta

关 键 词：信迪利单抗 安罗替尼 非小细胞肺癌 疗效 淋巴细胞亚群分析 CD137 

分 类 号：R734.2[医药卫生—肿瘤]