Risk of hepatitis B virus reactivation in B-cell malignancies treated with BTK inhibitors

Background In the era of immunotherapy, Bruton’s tyrosine kinase (BTK) inhibitors are increasingly used to treat B-cell malignancies. We aimed to investigate the reactivation of hepatitis B virus (HBV) in patients receiving BTK inhibitors. Methods Medical records were reviewed to identify patients with B cell malignancies treated with BTK inhibitors at Taizhou Hospital of Zhejiang Province between January 1, 2017, and July 31, 2024. Results A total of 91 patients with B-cell malignancies treated with BTK inhibitors were identified. Eleven patients were excluded due to anti-HBV prophylaxis, leaving 80 patients for further analysis. Among the 12 patients treated with ibrutinib, 9 (75%) had past HBV infections, and 2 (17%) had chronic HBV infections. Of the 40 patients treated with orelabrutinib, 21(52%) had past HBV infection, 2(5%) experienced HBV reactivation, and 5 (13%) had chronic HBV infections. Among the 28 patients treated with zanubrutinib, 21(75%) had past HBV infections, and no had chronic HBV infections. Conclusions This study is the first to document HBV reactivation associated with orelabrutinib (a second-generation BTK inhibitor) in a real-world setting. Regular monitoring of HBV status is crucial for patients receiving BTK inhibitors.