Targeting BTK in CLL: Beyond Ibrutinib

被引：109

作者：

Bond, David A. ^{[1
]}

Woyach, Jennifer A. ^{[1
]}

机构：

[1] Ohio State Univ, Dept Internal Med, Arthur G James Comprehens Canc Ctr, Div Hematol,Wexner Med Ctr, 445D Wiseman Hall CCC,410 W 12th Ave, Columbus, OH 43210 USA

来源：

CURRENT HEMATOLOGIC MALIGNANCY REPORTS | 2019年 / 14卷 / 03期

关键词：

Acalabrutinib; Tirabrutinib; Zanubrutinib; B cell receptor; CHRONIC LYMPHOCYTIC-LEUKEMIA; TYROSINE KINASE INHIBITOR; B-CELL RECEPTOR; ATRIAL-FIBRILLATION; VENTRICULAR-ARRHYTHMIAS; ACALABRUTINIB ACP-196; PLATELET ACTIVATION; CLONAL EVOLUTION; INITIAL THERAPY; RESISTANCE;

D O I：

10.1007/s11899-019-00512-0

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose of ReviewWhile the Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib has revolutionized the treatment of chronic lymphocytic leukemia (CLL), current limitations include off-target toxicities and the development of resistance. In this review, we summarize the emerging data for alternative BTKi.Recent FindingsSecond-generation BTKi include acalabrutinib, zanubrutinib, and tirabrutinib which offer greater BTK selectivity. While these agents may limit off-target toxicity, they do not overcome common mechanisms of ibrutinib resistance. Reversible BTKi including vecabrutinib and LOXO-305 inhibit BTK in the presence of C481S mutation, and non-selective reversible BTKi, including ARQ-531, may retain activity despite mutations within PLCG2. Early-phase studies are underway to establish the clinical efficacy and toxicity of these agents.SummaryA randomized trial of ibrutinib versus acalabrutinib is ongoing, and acalabrutinib may be an option for ibrutinib-intolerant patients. Results from ongoing trials of alternate BTKi will help to define their role in CLL therapy as single agents or in combination therapy.

引用

页码：197 / 205

页数：9

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