Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era

Abstract

Hepatitis due to hepatitis B virus (HBV) reactivation can be serious and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. Patients with inactive and even resolved HBV infection still have persistence of HBV genomes in the liver. The expression of these silent genomes is controlled by the immune system. Suppression or ablation of immune cells, most importantly B cells, may lead to reactivation of seemingly resolved HBV infection. Thus, all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen. Patients found to be positive for HBsAg should be given prophylactic antiviral therapy. For patients with resolved HBV infection, there are two approaches. The first is pre-emptive therapy guided by serial HBV DNA monitoring, and treatment with antiviral therapy as soon as HBV DNA becomes detectable. The second approach is prophylactic antiviral therapy, particularly for patients receiving high-risk therapy, especially anti-CD20 monoclonal antibody or hematopoietic stem cell transplantation. Entecavir and tenofovir are the preferred antiviral choices. Many new effective therapies for hematological malignancies have been introduced in the past decade, for example, chimeric antigen receptor (CAR)-T cell therapy, novel monoclonal antibodies, bispecific antibody drug conjugates, and small molecule inhibitors, which may be associated with HBV reactivation. Although there is limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, including Bruton’s tyrosine kinase inhibitors, B-cell lymphoma 2 inhibitors, and CAR-T cell therapy. Further studies are needed to determine the risk of HBV reactivation with these agents and the best prophylactic strategy.

Keywords: Hepatitis B; Hematologic neoplasms; Chimeric antigen receptor-T cell therapy; Monoclonal antibodies; Bruton’s tyrosine kinase inhibitors; Antiviral agents

Core Tip: Patients with chronic or past resolved hepatitis B virus (HBV) infection are at risk of reactivation of the virus when they receive chemotherapy or immunosuppressive therapy. Therefore, before treatment, patients should be screened for HBV markers, specifically hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen. Prophylactic antiviral therapy is important for HBsAg-positive patients, and is a reasonable option for patients with resolved HBV infection who are scheduled to receive high-risk therapy such as anti-CD20 monoclonal antibodies, anti-CD79 monoclonal antibodies, bispecific antibodies, chimeric antigen receptor-T cell therapy, or hematopoietic stem cell transplantation. For other patients with resolved HBV infection, pre-emptive antiviral therapy guided by serial monitoring of HBV DNA is a reasonable option.