替雷利珠单抗单药治疗复发或转移性头颈部鳞状细胞癌  

Tislelizumab monotherapy for the treatment of recurrent/metastatic head and neck squamous cell carcinoma

作　　者：宋攀 梁发雅[1] 叶煜初 黄永胜 伍韬玮 黄晓明[1] 韩萍[1] SONG Pan;LIANG Faya;YE Yuchu;HUANG Yongsheng;WU Taowei;HUANG Xiaoming;HAN Ping(Department of Otolaryngology Head and Neck Surgery,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Guangzhou,510289,China;Cellular&Molecular Diagnostics Center,Sun Yat-sen Memorial Hospital,Sun Yat-sen University)

机构地区：[1]中山大学孙逸仙纪念医院耳鼻咽喉头颈外科、广东省恶性肿瘤表观遗传学与基因调控重点实验室,广州510289 [2]中山大学孙逸仙纪念医院细胞分子诊断中心

出　　处：《临床耳鼻咽喉头颈外科杂志》2023年第10期778-785,共8页Journal of Clinical Otorhinolaryngology Head And Neck Surgery

基　　金：广东省基础与应用基础研究基金项目(No:2023A1515030042)。

摘　　要：目的评估替雷利珠单抗在复发/转移头颈鳞状细胞癌患者中的安全性和有效性。方法回顾性分析2018年1月—2020年6月在本院接受替雷利珠单抗单药治疗的复发/转移头颈鳞状细胞癌患者6例,收集性别、年龄、TNM分期、疗效、不良反应等信息。所有患者均来自RATIONALE 102研究,主要研究终点为客观缓解率,其他终点包括无进展生存期和总生存期等。对患者肿瘤组织进行了肿瘤免疫相关基因测序以及转录组测序分析,利用生物信息学方法进行免疫细胞富集及信号通路分析。所有分析均采用R语言4.1.0版、SPSS Statistics 24.0软件和GraphPad Prism 8完成。结果截至2020年5月31日,中位随访时间为26.35个月。替雷利珠单抗治疗的客观缓解率为50.0%,中位无进展生存期为6.44个月,估计中位生存期为20.07个月。3级以上不良反应发生率66.7%,包括低钠血症、低钾血症、高钙血症等。免疫治疗敏感患者的巨噬细胞、Treg和中性粒细胞相关基因表达较高,产生IgA的肠道免疫网络、移植物抗宿主病、自身免疫性甲状腺疾病等信号通路明显激活。结论替雷利珠单抗治疗复发或转移头颈鳞状细胞癌患者具有可控和可耐受的安全性,治疗反应与免疫细胞浸润及免疫相关信号通路的激活有关。Objective The aim of this retrospective study is to evaluate the safety and efficacy of tislelizumab in patients with recurrent/metastatic head and neck squamous cell carcinoma.Methods Six patients with recurrent/metastatic head and neck squamous cell carcinoma who received tislelizumab monotherapy in our hospital from 2018 to 2020 were retrospectively analyzed.The information of sex,age,TNM stage,efficacy,and adverse reactions were collected.All patients were recruited from the RATIONALE 102 study.The primary end point was the objective response rate,and other end points included progression-free survival and overall survival.We performed tumor immune-related gene sequencing and transcriptome sequencing analysis on the tumor tissues of the patient,and used bioinformatics methods to enrich immune cells and analyze signaling pathways.All analyses were performed using R 4.1.0 software,SPSS Statistics 24.0 software and GraphPad Prism 8.Results As of May 31,2020,the median follow-up time was 26.35 months.The objective response rate with tislelizumab was 50.0%,the median progression-free survival was 6.44 months,and the estimated median survival was 20.07 months.The incidence of grade 3 or higher adverse reactions was 66.7%,including hyponatremia,hypokalemia,hypercalcemia,etc.The expression of macrophage,Treg and neutrophil-related genes are higher in immune-sensitive patients,and the signaling pathways of the intestinal immune network for IgA production,graft versus host disease and autoimmune thyroid disease are significantly activated.Conclusion Tislelizumab was found to be controllable and tolerable in patients with recurrent/metastatic head and neck squamous cell carcinoma.The response to tislelizumab is related to immune cell infiltration and activation of immune-related signaling pathways.

关 键 词：头颈部肿瘤 替雷利珠单抗 免疫治疗 

分 类 号：R739.91[医药卫生—肿瘤]