Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Expert Rev Hematol. 2024 Jun;17(6):201-210. doi: 10.1080/17474086.2024.2356257. Epub 2024 May 24.
This review evaluates zanubrutinib as a treatment option for adults with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Zanubrutinib, a covalent BTK (Bruton's tyrosine kinase) inhibitor, was recently approved by the US FDA based in part on head-to-head data demonstrating improved efficacy and safety compared to ibrutinib.
The review discusses the efficacy, safety, and comparative advantages of zanubrutinib, highlighting its safety profile compared to other BTK inhibitors. It also addresses the unmet needs of current therapies in CLL/SLL and provides an overview of competitor compounds and ongoing research in BTK inhibition.
Zanubrutinib, the first BTK inhibitor to demonstrate superior efficacy and safety compared to another BTK inhibitor in CLL, is likely to be widely adopted due to its high-quality data and ease of use. Looking ahead, pirtobrutinib, a novel non-covalent BTK inhibitor, has shown promise in heavily pretreated CLL patients, including those unresponsive to covalent inhibitors, with ongoing phase 3 trials comparing it against ibrutinib. The field is also exploring time-limited therapies like the combination of ibrutinib and venetoclax, with ongoing trials evaluating different combinations to optimize efficacy and minimize toxicity, indicating a promising future for combination therapies in CLL treatment.
本综述评估了泽布替尼作为治疗成人慢性淋巴细胞白血病(CLL)/小淋巴细胞淋巴瘤(SLL)的一种选择。泽布替尼是一种共价 BTK(布鲁顿酪氨酸激酶)抑制剂,最近基于与伊布替尼头对头数据显示出改善的疗效和安全性,被美国 FDA 批准。
该综述讨论了泽布替尼的疗效、安全性和相对优势,强调了与其他 BTK 抑制剂相比其安全性概况。它还讨论了 CLL/SLL 中当前疗法的未满足需求,并概述了竞争化合物和 BTK 抑制的正在进行的研究。
泽布替尼是第一个在 CLL 中与另一种 BTK 抑制剂相比显示出优越疗效和安全性的 BTK 抑制剂,由于其高质量的数据和易用性,可能会被广泛采用。展望未来,新型非共价 BTK 抑制剂 pirtobrutinib 在包括对共价抑制剂无反应的预处理过的 CLL 患者中显示出前景,正在进行的 3 期试验将其与伊布替尼进行比较。该领域还在探索限时疗法,如伊布替尼和 venetoclax 的联合治疗,正在进行的试验评估不同的联合疗法以优化疗效并最小化毒性,表明组合疗法在 CLL 治疗中有一个充满希望的未来。