Feasibility of strategic monitoring in patients with prior HBV exposure undergoing anti-CD20 monoclonal antibody therapy: a prospective observational study

Abstract

Background: The use of anti-CD20 monoclonal antibody therapy for malignant and non-malignant diseases is increasing worldwide with the availability of biosimilars. The feasibility of a simple monitoring strategy based on hepatitis B virus (HBV) serology and liver biochemistry in hepatitis B surface antigen (HBsAg)-negative, antibody to the hepatitis B core antigen (anti-HBc)-positive individuals receiving rituximab-containing chemotherapy has not been explored. Methods: From October 2013 onwards, we recruited HBsAg-negative, anti-HBc-positive Asian patients with baseline undetectable serum HBV DNA (<20 IU/mL), diagnosed with lymphoid malignancies and receiving anti-CD20 monoclonal antibodies (rituximab, ofatumumab or obinutuzumab). Liver biochemistry, HBV serology and serum HBV DNA levels were prospectively monitored every 4 weeks up to 2 years. Upon HBV reactivation, defined by detectable HBV DNA, the monitoring interval was intensified to every 2 weeks. Entecavir was started upon active HBV disease, defined as either hepatitis B surface antigen (HBsAg) seroreversion, or biochemical hepatitis (alanine aminotransferase (ALT) >60 U/L for men, >38 U/L for women). This study was terminated in May 2017 upon territory-wide adaptation of antiviral prophylaxis in the Hong Kong public health system. Results: 83 consecutive HBsAg-negative, anti-HBc positive patients (mean age 68±11.4 years, 57.8% male), with a median follow-up duration of 68 (range 4-104) weeks, were recruited. In this interim analysis of 70 patients, the cumulative 2-year HBV reactivation rate calculated by the Kaplan-Meier method was 23.3%, with the median HBV DNA level at reactivation 94 (range 22-1040) IU/mL. Patients with negative antibody to HBsAg (anti-HBs) levels, when compared to anti-HBs positive patients, had a significantly higher rate of reactivation (41.2% vs 15.0%, p=0.005). Among the 14 patients (20.0%) who developed reactivation, 7 (50%) progressed to active HBV disease after a median duration of 9 (range 2-16) weeks (median HBV DNA 69,600 IU/mL), of which 6 (85.7%) developed HBsAg seroreversion and 5 (71.4%) developed biochemical hepatitis (ALT ranging 32-96 U/L). Entecavir successfully controlled all 7 cases of active HBV with subsequent ALT normalization and HBV DNA becoming undetectable, without any cases of hepatic decompensation. Conclusion: In occult viral carriers receiving anti-CD20 monoclonal antibodies, regular monitoring of liver biochemistry and HBV serology could be a feasible alternative to antiviral prophylaxis or HBV DNA monitoring, especially in resource-constrained regions. (ClinicalTrials.gov identifier NCT 03155984).