Efficacy and Safety of the Bruton's Tyrosine Kinase Inhibitor Zanubrutinib in Immune Thrombocytopenia

ABSTRACT Immune thrombocytopenia (ITP) is characterized by impaired platelet production and increased platelet destruction. Zanubrutinib is a highly selective next‐generation Bruton tyrosine kinase (BTK) inhibitor that may reduce autoantibody production and reduce macrophage Fcγ receptor‐mediated platelet destruction. In this single‐arm, phase II study, we aimed to assess the efficacy and safety of zanubrutinib in corticosteroid‐resistant or relapsed ITP. All patients received 80 mg zanubrutinib once daily for 6 weeks followed by a 20‐week safety follow‐up period. The primary endpoint was overall response (OR), defined as at least two consecutive platelet counts of at least 30 × 10 9 /L, at least a 2‐fold increase in the baseline count, the absence of bleeding, and no need for rescue therapy at 4 weeks. The trial was registered with ClinicalTrials.gov , number NCT05279872. Between January 1, 2022 and October 30, 2022, 20 patients were enrolled. The median platelet count was 19 (10–25) × 10 9 /L at the time of enrollment. Participants had received a median of 4 (3–6) different therapies for ITP. Eleven (55%, 95% CI: 31.5%–76.9%) patients achieved an OR to the intervention. Two (10%) patients achieved a complete response. At the 6‐month follow‐up, a sustained response was achieved in seven (35.0%, 95% CI: 15.4%–59.2%) patients. There were no grade 4 or worse adverse events or treatment‐related deaths. The most common adverse events were upper respiratory tract infection (in 25% of the patients). Zanubrutinib showed an encouraging response rate and tolerability, supporting its therapeutic potential for the treatment of ITP. Trial Registration: ClinicalTrials.gov identifier: NCT05279872.