Vitale Candida, Gibbons Jamie Lynn, Ferrajoli Alessandra
Department of Molecular Biotechnology and Health Sciences, University of Torino and University Division of Hematology, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy.
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Onco Targets Ther. 2021 Dec 29;14:5507-5519. doi: 10.2147/OTT.S303060. eCollection 2021.
In chronic lymphocytic leukemia (CLL), a deeper understanding of the disease biology led over the last decade to the development and clinical use of different targeted drugs, including Bruton tyrosine kinase (BTK) inhibitors. The first BTK inhibitor approved for clinical use is ibrutinib, which showed excellent efficacy and good tolerability. More recently, the interest is growing for novel more selective BTK inhibitors that may reduce the off-target effects of the drug, thus minimizing side effects and subsequent treatment interruptions or discontinuations. Acalabrutinib is an orally administered irreversible BTK inhibitor, characterized by the lack of inhibition towards other kinases. In this review, we present the most recent data from clinical trials on the clinical efficacy of acalabrutinib and acalabrutinib-based combinations for the treatment of patients with relapsed/refractory and treatment-naïve CLL. We delineate the safety profile of the drug, describe side effects of interest and discuss the clinical management of patients receiving acalabrutinib. Due to its efficacy and the favorable safety profile, acalabrutinib has emerged as a viable therapy option in the current landscape of multiple approved treatments for CLL.
在慢性淋巴细胞白血病（CLL）中，过去十年间对疾病生物学的深入理解促使了包括布鲁顿酪氨酸激酶（BTK）抑制剂在内的多种靶向药物的研发与临床应用。首个获批临床使用的BTK抑制剂是伊布替尼，它展现出了卓越的疗效和良好的耐受性。最近，人们对新型、更具选择性的BTK抑制剂兴趣日增，这类抑制剂可能会减少药物的脱靶效应，从而将副作用以及后续治疗中断或停药的情况降至最低。阿卡拉布替尼是一种口服的不可逆BTK抑制剂，其特点是对其他激酶无抑制作用。在本综述中，我们展示了关于阿卡拉布替尼及其联合用药治疗复发/难治性和初治CLL患者临床疗效的最新临床试验数据。我们阐述了该药物的安全性概况，描述了相关副作用，并讨论了接受阿卡拉布替尼治疗患者的临床管理。鉴于其疗效和良好的安全性，在目前多种获批用于CLL治疗的药物格局中，阿卡拉布替尼已成为一种可行的治疗选择。
