Hepatitis B virus reactivation in cancer patients with positive Hepatitis B surface antigen undergoing PD-1 inhibition

• Published in: Journal for immunotherapy of cancer Vol. 7; no. 1; pp. 322 - 10
• Main Authors: Zhang, Xuanye, Zhou, Yixin, Chen, Chen, Fang, Wenfeng, Cai, Xiuyu, Zhang, Xiaoshi, Zhao, Ming, Zhang, Bei, Jiang, Wenqi, Lin, Zuan, Ma, Yuxiang, Yang, Yunpeng, Huang, Yan, Zhao, Hongyun, Xu, Ruihua, Hong, Shaodong, Zhang, Li
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 21.11.2019; BioMed Central Ltd; BMJ Publishing Group LTD; BioMed Central; BMJ Publishing Group
• Subjects: Alcoholism; Antibodies; Antigens; Antiviral agents; Apoptosis; Biochemistry; Cancer; Cancer patients; Cancer therapies; Care and treatment; Cell death; Checkpoint; Chemotherapy; Clinical trials; Clinical/Translational Cancer Immunotherapy; Cytotoxicity; Disease prevention; DNA; Health aspects; Hepatitis A; Hepatitis B; Hepatitis B virus; Hepatitis C; Hepatitis delta virus; HIV; Human immunodeficiency virus; Immunosuppressive agents; Immunotherapy; Infection; Infections; Ligands; Liver cancer; Liver cirrhosis; Medical research; Patients; PD-1; PD-L1; Prophylaxis; Reactivation; Regulatory approval; Research Article; Safety; Steroids; Viruses; United States > US; Checkpoint; Reactivation; Immunotherapy; PD-L1; Hepatitis B virus; Safety; PD-1; Cancer
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1186/s40425-019-0808-5

BackgroundHepatitis B virus (HBV) reactivation is a serious complication in patients with cancers and HBV infection undergoing immunosuppressant treatment or chemotherapy. However, the safety of anti-programmed cell death (PD) -1 and anti-programmed cell death-ligand 1 (PD-L1) therapy in these patients is unknown because they were excluded from clinical trials of immunotherapy.MethodsThis retrospective cohort study involved consecutive hepatitis B surface antigen (HBsAg) -positive cancer patients who were referred to Sun Yat-sen University Cancer Center and received an anti-PD-1/PD-L1 antibody between January 1, 2015 and July 31, 2018. The primary end point was the rate of the occurrence of HBV reactivation.ResultsIn total, 114 eligible patients were included, among whom 90 (79%) were male, and the median (range) age was 46 (16–76) years. Six patients (5.3%) developed HBV reactivation, occurring at a median of 18 weeks (range, 3–35 weeks) from the commencement of immunotherapy. Among these patients, all of them had undetectable baseline HBV DNA; one had prophylactic antiviral therapy while five did not; four were positive for Hepatitis B e antigen while the other two were negative. At reactivation, the median HBV DNA level was 3.89 × 104 IU/mL (range, 1.80 × 103–6.00 × 107 IU/mL); five had HBV-related hepatitis and one exhibited increasing HBV DNA level without alanine transaminase elevation. No HBV-related fatal events occurred. The lack of antiviral prophylaxis was the only significant risk factor for HBV reactivation (odds ratio, 17.50 [95% CI, 1.95–157.07], P = .004).ConclusionsHBV reactivation occurs in a subset of HBsAg-positive cancer patients undergoing anti-PD-1 or anti-PD-L1 immunotherapy. Regular monitoring of HBV DNA and antiviral prophylaxis are advised to prevent this potentially fatal complication.