# Hepatitis B virus reactivation in patients with hematologic malignancies treated with Bruton tyrosine kinase inhibitors

## TL;DR

This study reports cases of hepatitis B virus reactivation in cancer patients treated with BTK inhibitors, highlighting a potential risk and the need for monitoring.

## Contribution

First report of HBV-related death in patients from HBV-endemic areas treated with BTKis and first case of reactivation despite entecavir prophylaxis.

## Key findings

- HBV reactivation occurred in patients with CLL and MCL treated with BTKis.
- One patient with MCL experienced reactivation despite entecavir and tenofovir prophylaxis.
- A patient with CLL died from hepatorenal syndrome linked to HBV reactivation.

## Abstract

Bruton tyrosine kinase inhibitors (BTKis) are effective and well-tolerated treatments for chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Here, we describe the clinical characteristics of hepatitis B virus (HBV) reactivation in patients with hematological malignancies treated with BTKis.

Patients were required to have a pathologically confirmed diagnosis of CLL or MCL, receive at least one cycle of ibrutinib or zanubrutinib, and have either positive hepatitis B surface antigen or hepatitis B core antibody at diagnosis. Patients were excluded if they had received rituximab or obinutuzumab within the previous 12 months.

We identified five patients with CLL and one with MCL who had resolved HBV infections and received BTKis during the study period. None of the patients received anti-HBV prophylaxis after CLL diagnosis. The patient with MCL who received zanubrutinib was confirmed to have HBV reactivation even after prophylactic entecavir administration followed by tenofovir. All five patients with CLL received ibrutinib as second-line therapy. A 62-year-old man died of hepatorenal syndrome associated with HBV reactivation despite entecavir treatment.

To the best of our knowledge, this is the first description of HBV-related death in patients receiving BTKis from HBV-endemic areas, and the first case of HBV reactivation associated with zanubrutinib despite previous entecavir prophylaxis. Further prospective studies are warranted to develop useful guidelines for monitoring HBV DNA and antiviral prophylaxis to prevent HBV reactivation after BTKi therapy.