Zhao Jian, Zhang Yuehua, Qin Siyuan, Zou Bingwen, Wang Yongsheng
Clinical Trial Center, National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041 P.R. China.
West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
J Cancer. 2022 Oct 31;13(14):3539-3553. doi: 10.7150/jca.77247. eCollection 2022.
Immune checkpoint inhibitor (ICI) therapy is now administered to patients with advanced cancers. However, the safety and efficacy of ICIs in cancer patients with hepatitis B virus (HBV) infection is unknown. Therefore, we performed this systematic review to examine the safety and efficacy of ICIs in patients with HBV infection, with particular focus on HBV reactivation. Studies examining ICI treatment in patients with advanced cancer and HBV infection in PubMed from database inception to April 2022 were retrieved in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In addition, reports of individuals diagnosed with HBV reactivation were supplemented through the Food and Drug Administration Adverse Event Reporting System. We identified 20 articles (8 case reports, 10 retrospective case series, and 2 prospective clinical trials) and 2 meeting abstracts including 633 patients with advanced cancer and HBV infection treated with ICIs. The overall rate of HBV reactivation was 4.1% (26/633), and no HBV-related fatal events were reported. Among patients with HBV reactivation with known baseline data (20/26), HBV-DNA returned to undetectable status in 15 of 17 patients (88.2%) after a median 5.5 weeks (range, 1-14 weeks). Therapeutic responses to ICIs were observed in 14 of 88 patients (15.91%) with hepatocellular carcinoma, 6 of 45 patients (13.33%) with non-small cell lung cancer, and 3 of 13 patients (23.08%) with melanoma. ICIs may be safe and effective in patients with advanced cancer and HBV infection. However, there is still a need for clinical monitoring of liver enzymes and HBV-DNA during ICI therapy. Prospective trials are necessary to elucidate the appropriate antiviral therapy in these patients.
免疫检查点抑制剂（ICI）疗法目前已应用于晚期癌症患者。然而，ICI在乙型肝炎病毒（HBV）感染的癌症患者中的安全性和疗效尚不清楚。因此，我们进行了这项系统评价，以研究ICI在HBV感染患者中的安全性和疗效，特别关注HBV再激活。按照系统评价和Meta分析的首选报告项目指南，检索了从数据库建立至2022年4月在PubMed中关于晚期癌症和HBV感染患者ICI治疗的研究。此外，通过美国食品药品监督管理局不良事件报告系统补充了被诊断为HBV再激活的个体报告。我们确定了20篇文章（8篇病例报告、10篇回顾性病例系列和2篇前瞻性临床试验）以及2篇会议摘要，包括633例接受ICI治疗的晚期癌症和HBV感染患者。HBV再激活的总体发生率为4.1%（26/633），未报告与HBV相关的致命事件。在有已知基线数据的HBV再激活患者中（20/26），17例患者中的15例（88.2%）在中位5.5周（范围1 - 14周）后HBV-DNA恢复到不可检测状态。88例肝细胞癌患者中有14例（15.91%）、45例非小细胞肺癌患者中有6例（13.33%）、13例黑色素瘤患者中有3例（23.08%）观察到对ICI的治疗反应。ICI在晚期癌症和HBV感染患者中可能是安全有效的。然而，在ICI治疗期间仍需要对肝酶和HBV-DNA进行临床监测。有必要进行前瞻性试验以阐明这些患者的适当抗病毒治疗。
