使用程序性死亡受体-1单克隆抗体治疗肝癌肝移植术后复发的临床策略  

Clinical strategy of programmed death-1 monoclonal antibody in patients with recurrent liver cancer after liver transplantation

作　　者：鲁旭 张英才[1] 李华[1] 赵辉[1] 李海波 张剑文[1] 邱春辉[1] 易述红[1] 汪根树[1] 张剑[1] 杨扬[1] 陈规划[1] 汪国营[1] Lu Xu;Zhang Yingcai;Li Hua;Zhao Hui;Li Haibo;Zhang Jianwen;Qiu Chunhui;Yi Shuhong;Wang Genshu;Zhang Jian;Yang Yang;Chen Guihua;Wang Guoying(Department of Hepatic Surgery,Liver Transplantation Center,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China)

机构地区：[1]中山大学附属第三医院肝脏外科暨肝脏移植中心,广州510630

出　　处：《中华移植杂志（电子版）》2021年第6期334-340,共7页Chinese Journal of Transplantation(Electronic Edition)

基　　金：十三五科技重大专项(2017ZX10203205-006-001);陈孝平科技发展基金(CXPJJH12000001-2020218)。

摘　　要：目的探讨肝癌肝移植术后复发患者安全应用程序性死亡受体-1(PD-1)单克隆抗体(以下简称单抗)的治疗策略。方法本研究纳入4例一线靶向药物治疗后肿瘤仍进展的肝癌肝移植术后复发患者,进行移植肝穿刺免疫组织化学检测程序性死亡配体-1(PD-L1)表达均为阴性。患者接受PD-1抑制剂卡瑞利珠单抗治疗,每3周1次,200 mg/次,并选择合适的靶向药物联合治疗,同时将免疫抑制方案调整为哺乳动物雷帕霉素靶蛋白(mTOR)抑制剂联合霉酚酸类药物。随访期间综合分析患者肝功能、甲胎蛋白(AFP)以及胸腹部影像学检查等变化情况,评估PD-1单抗的有效性与安全性。结果截至2021年2月,4例患者中存活2例,分别随访17.3和15.3个月,期间均接受PD-1单抗治疗6次,有乏力、腹泻和高血压等不良反应,经对症治疗后均好转,仍处于持续随访中。病例1因肺部转移瘤压迫气管和支气管引起严重肺部感染,于PD-1单抗治疗后6.3个月死亡(期间共接受PD-1单抗治疗6次);病例4因肺部转移瘤压迫支气管引起肺炎、肺不张和双侧胸水,于PD-1单抗治疗后10.9个月死亡(期间共接受PD-1单抗治疗3次)。4例患者使用PD-1单抗治疗后,AST水平均处于相对稳定状态,偶有波动也可通过护肝治疗较快恢复正常;血清白蛋白波动于30~45 g/L;总胆红素处于正常水平,均未发生黄疸;3例患者AFP均有不同程度下降。随访期间患者均未发生明显排斥反应。使用PD-1单抗治疗后,改良的实体肿瘤疗效评价标准评估3例患者为疾病稳定,中位无进展生存期为141 d;另1例患者评估为部分缓解,中位无进展生存期为180 d。结论移植肝组织PD-L1表达阴性的肝癌肝移植术后复发患者,在mTOR抑制剂联合霉酚酸类药物维持有效免疫抑制状态下使用PD-1单抗是相对安全的,但其有效性与长期临床获益仍需进一步观察。Objective To investigate the safe application of programmed death-1(PD-1)monoclonal antibody in patients with recurrent liver cancer after liver transplantation.Methods Four patients with recurrent hepatocellular carcinoma after liver transplantation who still progressed after first-line targeted drug therapy were included in this study,and programmed death ligand-1(PD-L1)expression was negative by immunohistochemistry of liver allograft puncture.Patients were treated with the PD-1 inhibitor Camrelizumab,200 mg every 3 weeks,and the appropriate targeted drug combination was selected,while the immunosuppressive regimen was adjusted to mammalian target of rapamycin(mTOR)inhibitors in combination with mycophenolate mofetil.Blood routine,liver and kidney function,alpha-fetoprotein(AFP)and thoracic and abdominal imaging examinations were measured during follow-up,and changes in liver function and tumor parameters during follow-up were comprehensively analyzed to evaluate the efficacy and safety of PD-1 monoclonal antibody.Results By February 2021,2 of the 4 patients survived and were followed up for 17.3 and 15.3 months,respectively,during which they all received PD-1 monoclonal antibody for 6 times,with adverse reactions such as fatigue,diarrhea and hypertension,which were improved after symptomatic treatment and are still under continuous follow-up.In Case 1,the patient died 6.3 months after PD-1 monoclonal antibody treatment due to severe lung infection caused by compression of trachea and bronchus by pulmonary metastases(a total of 6 times of PD-1 monoclonal antibody treatment were performed during this period);in Case 4,the patient died 10.9 months after PD-1 monoclonal antibody treatment due to pneumonia,atelectasis and pleural effusion caused by compression of bronchus by pulmonary metastases(a total of 3 times of PD-1 monoclonal antibody treatment were performed during this period).Four patients were treated with PD-1 monoclonal antibody.However,AST levels were in a relatively stable state,and occasional fluct

关 键 词：肝细胞癌 肝移植 靶向药物 程序性死亡受体-1抑制剂 

分 类 号：R735.7[医药卫生—肿瘤]