晚期肝细胞癌免疫治疗的相关不良反应  

Adverse reactions related to immunotherapy for advanced hepatocellular carcinoma

作　　者：乔师师[1] 郭化虎 杨振[1] 潘延凤[1] 孔天东[2] 于丹 赵玲娣[4] QIAO Shi-shi;GUO Hua-hu;YANG Zheng;PAN Yan-feng;KONG Tian-dong;YU Dan;ZHAO Ling-di(Department of Hepatobiliary an Pancreatic Surgery,First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,Henan,China)

机构地区：[1]郑州大学第一附属医院肝胆胰外科,河南郑州450052 [2]河南大学肿瘤医院肿瘤科,河南郑州450052 [3]郑州市颐和医院肿瘤科,河南郑州450052 [4]河南省肿瘤医院肿瘤科,河南郑州450052

出　　处：《广东医学》2023年第3期369-373,共5页Guangdong Medical Journal

基　　金：河南省医学科技攻关计划项目(SB201901026)。

摘　　要：目的探讨晚期肝细胞癌患者采用免疫检查点抑制剂治疗时出现免疫相关不良反应的概率及应对以及对疗效的影响。方法回顾性分析收治的、接受以PD-1/PD-L1抗体或联合CTLA-4为基础治疗的晚期肝细胞癌患者的临床特点、不良反应发生率,及应对措施,并通过电话、微信等方式进行随访。结果63例患者中,男54例,女9例;中位年龄54(33~82)岁。单用PD-1/PD-L1抗体者13例,联合仑伐替尼者14例,联合阿帕替尼者23例,联合贝伐单抗者9例,联合卡培他滨者4例;其中一线接受以PD-1抗体为基础治疗者40例,二线者为14例,三线及以后9例。63例患者中23例患者乙肝病史>20年,11例患者乙肝病史10~20年,乙肝病史10年以下者26例;另有2例为丙型肝炎患者,1例无病毒性肝炎病史。63例患者中完全缓解3例,部分缓解14例,疾病稳定31例,疾病进展15例,客观有效率为26.9%,疾病控制率为76.2%。治疗过程中不良反应整体发生率为77.8%(49/63),其中3~4级不良反应发生率为15.8%(10/63),免疫相关不良反应发生率为53.9%(34/63),其中3~4级免疫相关不良反应发生率为4.7%(3/63),无治疗相关死亡。63例患者中位无进展生存期为5.2(95%可信区间4.0~6.1)个月,中位生存期11.7(95%可信区间6.8~16.1)个月。进一步分析发现:免疫治疗前患者肝功能Child评分和患者体能状态评分是影响患者疗效和生存时间的主要因素;多因素分析显示治疗前患者的体能状态评分和肝功能Child评分是影响患者生存的独立预后因素(P值分别为<0.001和0.034)。结论以免疫检查点抑制剂为基础的免疫治疗在晚期肝癌患者中是安全有效的;1~2级免疫相关不良反应发生率高,但不影响疗效;3~4级免疫相关不良反应发生率低,但需要认真对待避免出现严重后果。Objective To investiagte the efficacy,safety and adverse reactions of immunocheckpoint inhibitor(ICI)based therapy in advanced hepatocellular carcinoma.Methods The clinical features,efficacy and safety in patients with advanced hepatocellular carcinoma who received anti-PD-1/PD-L1 antibody or anti-CTLA-4 antibody based therapy were retrospectively analyzed.The survival status were followed-up by telephone or WeChat.Results Among the 63 patients,13 cases received anti-PD-1 antibody monotherapy;14 cases of combined treatment with lenvatinib,23 cases with apatinib,4 cases with cabozantinib;and 9 cases received anti-PD-1 antibody plus anti-CTLA-4 antibody.The median age of the patients was 54 years old(33-82 years old)and mainly male(54 were male).Forty patients received anti-PD-1 antibody based therapy as first line therapy,14 patients received anti-PD-1 antibody based therapy as second line therapy,and 9 cases as third or later line therapy.Amont the 63 patients,23 patients had a history of hepatitis B for more than 20 years,and 37 patients had a history of hepatitis B less than 10 years,2 patient had a history of hepatitis C,and the left one had no history of viral hepatitis.Complete response was achieved in 3 patients,partial response was achieved in 14 patients,stable disease was achieved in 31 patients,and the diseases progressed in 15 patients.The objective response rate was 26.9%,and the disease control rate was 76.2%.The overall incidence of adverse events during treatment was 77.8%(49/63),of which the incidence of Grade 3-4 adverse events was 15.8%(10/63).The incidence of immune-related adverse events was 53.9%(34/63)and the incidence of Grade 3-4 immune-related adverse events was 4.7%(3/63),and there was no treatment-related death.The median progression-free survival of the 63 patients was 5.2 months(95%confidential interval 4.0-6.1 months),and the median overall survival was 11.7 months(95%confidential interval 6.8-16.1 months).Univariate and multivariate analysis showed that liver function Child scores a

关 键 词：肝细胞肝癌 免疫检查点抑制剂 免疫相关不良反应 

分 类 号：R735.7[医药卫生—肿瘤] R73-31[医药卫生—临床医学]