Department of Experimental Hematology, Medical University of Lodz, Lodz, Poland.
Department of Hematooncology, Copernicus Memorial Hospital, Lodz, Poland.
Expert Rev Hematol. 2022 Mar;15(3):183-194. doi: 10.1080/17474086.2022.2054800. Epub 2022 Mar 29.
The first-in-class Bruton tyrosine kinase (BTK), ibrutinib, demonstrated remarkable activity in chronic lymphocytic leukemia (CLL). However, its toxicity profile renders it potentially inappropriate for use in patients with bleeding or cardiovascular disorders. In response to the high demand for a safer and efficient BTK inhibitor, with improved toxicity profile, acalabrutinib as a second-generation irreversible BTK inhibitor has been approved for the treatment of CLL.
This review examines the activity of acalabrutinib in treating treatment-naïve and relapsed refractory CLL and its toxicity profile when compared to ibrutinib and other drugs. It will examine the outcomes of the ELEVATE-TN, ASCEND, and ELEVATE-RR studies in detail, with a particular focus on the safety and efficacy of acalabrutinib. The strengths and weaknesses of this drug will be highlighted and future directions for research will be identified.
In patients with CLL, acalabrutinib demonstrates a superior safety profile than ibrutinib and similar activity. In the first direct comparison of acalabrutinib with ibrutinib in relapsed/refractory CLL, acalabrutinib was found to demonstrate non-inferior progression-free survival, with fewer cardiovascular adverse events.
首个布鲁顿酪氨酸激酶(BTK)抑制剂伊布替尼在慢性淋巴细胞白血病(CLL)中显示出显著的疗效。然而,其毒性特征使其在有出血或心血管疾病的患者中可能不适用。为了满足对更安全、更有效的 BTK 抑制剂的高需求,具有改善的毒性特征的第二代不可逆 BTK 抑制剂阿卡鲁替尼已被批准用于治疗 CLL。
本综述考察了阿卡鲁替尼在治疗初治和复发难治性 CLL 中的活性及其与伊布替尼和其他药物相比的毒性特征。它将详细研究 ELEVATE-TN、ASCEND 和 ELEVATE-RR 研究的结果,特别关注阿卡鲁替尼的安全性和疗效。将突出该药物的优势和劣势,并确定未来的研究方向。
在 CLL 患者中,阿卡鲁替尼的安全性优于伊布替尼,且活性相当。在复发/难治性 CLL 中,阿卡鲁替尼与伊布替尼的首次直接比较中,阿卡鲁替尼显示出非劣效的无进展生存期,且心血管不良事件更少。