Orelabrutinib是一种新型的、小分子、选择性不可逆的布鲁顿酪氨酸激酶抑制剂。本研究旨在评估该药物在难治性或复发性慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/SLL）患者中的疗效和安全性。这是一项单臂、多中心、开放标签、2期临床试验，共有80名符合资格的中国患者接受monotherapy 治疗，每日150mg的orelabrutinib。独立审查委员会评估的总体缓解率是主要终点，次要终点包括无进展生存期、总体生存期和安全性。独立审查委员会评估到的总体缓解率为92.5%（74/80）；完全缓解率为21.3%（17/80），部分缓解率为60.0%（48/80），淋巴细胞增生型的部分缓解率为11.3%（9/80）。在32.3个月的中位随访期内，中位无进展生存期尚未达到，而30个月的无进展生存率和总体生存率分别为70.9%（95%置信区间[CI]，59.5-79.6）和81.3%（95% CI，70.8-88.2）。Orelabrutinib在高预后风险患者中也显示了显著的疗效：携带阳性TP53突变状态或del（17p）、del（11q）以及不突变的免疫球蛋白重链可变区基因的患者总体反应率分别为100%、94.7%和93.9%。大多数不良事件为低级别，86.8%的AE为1级或2级。近67%的患者在近3年的随访后仍在接受orelabrutinib治疗。总之，Orelabrutinib展示了令人信服的疗效和安全性，有相当数量的难治性或复发性CLL/SLL患者获得了完全缓解。©2023 Wiley Periodicals LLC。

Orelabrutinib is a novel, small molecule, selective irreversible Bruton's tyrosine kinase inhibitor. The aim of this study was to evaluate the efficacy and safety in patients with refractory or relapsed chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). This is single-arm, multi-center, open-label, phase 2 study in 80 eligible Chinese patients, who were treated with monotherapy of orelabrutinib at 150 mg once daily. Overall response rate evaluated by an independent review committee was the primary endpoint, and secondary endpoints include progression-free survival, overall survival, and safety. Independent review committee assessed overall response rate was 92.5% (74/80); complete response 21.3% (17/80), partial response 60.0% (48/80), partial response with lymphocytosis 11.3% (9/80). At a 32.3-month median follow-up, the median progression-free survival had not been achieved, while the 30-month progression-free survival rate and overall survival rates were 70.9% (95% confidence interval [CI], 59.5-79.6) and 81.3% (95% CI, 70.8-88.2), respectively. Orelabrutinib also revealed substantial response in patients with high prognostic risks: overall response rates of patients carrying positive TP53 mutational status or del(17p), del(11q), as well as unmutated immunoglobulin heavy-chain variable region gene were 100%, 94.7%, and 93.9%, respectively. Most adverse events were in low grade, with 86.8% of AEs being Grade 1 or 2. Nearly 67% of patients were still receiving orelabrutinib after almost a 3-year follow-up. In conclusion, Orelabrutinib demonstrated compelling efficacy as well as safety profiles, with a noteworthy number of patients obtaining complete response in refractory or relapsed CLL/SLL.© 2023 Wiley Periodicals LLC.