Overcoming Ibrutinib Resistance in Chronic Lymphocytic Leukemia

被引：39

作者：

Pula, Bartosz ^{[1
]}

Golos, Aleksandra ^{[2
]}

Gorniak, Patryk ^{[3
]}

Jamroziak, Krzysztof ^{[1
]}

机构：

[1] Inst Hematol & Transfus Med, Dept Hematol, PL-02776 Warsaw, Poland

[2] Inst Hematol & Transfus Med, PL-02776 Warsaw, Poland

[3] Inst Hematol & Transfus Med, Dept Expt Hematol, PL-02776 Warsaw, Poland

来源：

CANCERS | 2019年 / 11卷 / 12期

关键词：

Bruton's tyrosine kinase; ibrutinib; chronic lymphocytic leukemia; treatment; resistance; B-CELL-RECEPTOR; TYROSINE KINASE INHIBITOR; BTK INHIBITOR; ATRIAL-FIBRILLATION; ACQUIRED-RESISTANCE; CLONAL EVOLUTION; APOPTOTIC CELLS; PLUS RITUXIMAB; NUCLEAR EXPORT; ADVERSE EVENTS;

D O I：

10.3390/cancers11121834

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Ibrutinib is the first Bruton's tyrosine kinase (BTK) inhibitor, which showed significant clinical activity in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) patients regardless of cytogenetic risk factors. Recent results of phase III clinical trials in treatment-naive CLL patients shift the importance of the agent to frontline therapy. Nevertheless, beside its clinical efficacy, ibrutinib possesses some off-target activity resulting in ibrutinib-characteristic adverse events including bleeding diathesis and arrhythmias. Furthermore, acquired and primary resistance to the drug have been described. As the use of ibrutinib in clinical practice increases, the problem of resistance is becoming apparent, and new methods of overcoming this clinical problem arise. In this review, we summarize the mechanisms of BTK inhibitors' resistance and discuss the post-ibrutinib treatment options.

引用

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