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

IF 10.1 1区 医学 Q1 HEMATOLOGY
Qiu-Sha Huang, Hai-Xia Fu, Chen-Cong Wang, Xiao-Lu Zhu, Yun He, Jin Wu, Qi Chen, Peng Zhao, Zhuo-Yu An, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Hui Zhang
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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 × 109/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) × 109/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.
布鲁顿酪氨酸激酶抑制剂扎鲁替尼治疗免疫性血小板减少症的疗效和安全性
免疫性血小板减少症(ITP)的特点是血小板产生受损和血小板破坏增加。Zanubrutinib是一种高选择性的下一代布鲁顿酪氨酸激酶(BTK)抑制剂,可以减少自身抗体的产生和减少巨噬细胞Fcγ受体介导的血小板破坏。在这项单组II期研究中,我们旨在评估扎鲁替尼治疗皮质类固醇抵抗性或复发性ITP的有效性和安全性。所有患者接受80mg zanubrutinib,每天一次,持续6周,随后是20周的安全随访期。主要终点是总体缓解(OR),定义为至少连续两次血小板计数至少为30 × 109/L,基线计数至少增加2倍,无出血,4周时不需要抢救治疗。该试验已在ClinicalTrials.gov注册,注册号NCT05279872。在2022年1月1日至2022年10月30日期间,20名患者入组。入组时中位血小板计数为19 (10-25)× 109/L。参与者接受了中位数为4(3-6)种不同的ITP治疗。11例(55%,95% CI: 31.5%-76.9%)患者达到OR。2例(10%)患者获得完全缓解。在6个月的随访中,7例患者(35.0%,95% CI: 15.4%-59.2%)获得持续缓解。没有4级或更严重的不良事件或与治疗相关的死亡。最常见的不良事件是上呼吸道感染(25%的患者)。扎努鲁替尼显示出令人鼓舞的反应率和耐受性,支持其治疗ITP的治疗潜力。
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来源期刊
CiteScore
15.70
自引率
3.90%
发文量
363
审稿时长
3-6 weeks
期刊介绍: The American Journal of Hematology offers extensive coverage of experimental and clinical aspects of blood diseases in humans and animal models. The journal publishes original contributions in both non-malignant and malignant hematological diseases, encompassing clinical and basic studies in areas such as hemostasis, thrombosis, immunology, blood banking, and stem cell biology. Clinical translational reports highlighting innovative therapeutic approaches for the diagnosis and treatment of hematological diseases are actively encouraged.The American Journal of Hematology features regular original laboratory and clinical research articles, brief research reports, critical reviews, images in hematology, as well as letters and correspondence.
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