Understanding resistance mechanisms to BTK and BCL2 inhibitors in mantle cell lymphoma: implications for design of clinical trials

被引：17

作者：

Agarwal, Rishu ^{[1
,2
]}

Dawson, Mark A. ^{[1
,2
,3
,4
]}

Dreyling, Martin ^{[5
]}

Tam, Constantine S. ^{[2
,3
,6
,7
]}

机构：

[1] Peter MacCallum Canc Ctr, Div Canc Res, Melbourne, Vic, Australia

[2] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia

[3] Peter MacCallum Canc Ctr, Div Canc Med, Melbourne, Vic 3000, Australia

[4] Univ Melbourne, Ctr Canc Res, Parkville, Vic, Australia

[5] Ludwig Maximilians Univ Munchen, Univ Hosp, Dept Med 3, Munich, Germany

[6] St Vincents Hosp, Dept Haematol, Fitzroy, Vic, Australia

[7] Univ Melbourne, Dept Med, Parkville, Vic, Australia

来源：

LEUKEMIA & LYMPHOMA | 2018年 / 59卷 / 12期

基金：

英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;

关键词：

Mantle cell lymphoma; ibrutinib; venetoclax; resistance mechanisms; CHRONIC LYMPHOCYTIC-LEUKEMIA; IBRUTINIB PLUS VENETOCLAX; PROGRESSION-FREE SURVIVAL; BRUTONS TYROSINE KINASE; HIGH-DOSE CYTARABINE; TERM-FOLLOW-UP; RANDOMIZED-TRIALS; OPEN-LABEL; INVESTIGATORS CHOICE; ACQUIRED MUTATIONS;

D O I：

10.1080/10428194.2018.1457148

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Novel targeted therapeutics has significantly improved the outlook of patients with relapsed/refractory mantle cell lymphoma (R/R MCL). Despite significant efficacy, one of the major limitations of these targeted agents is presence of primary or acquired resistance to these novel drugs. Patients who fail primary therapy especially with ibrutinib have poor outcomes and may respond poorly to subsequent therapies. Hence, it is important to understand resistance mechanisms a priori to identify patients who are unlikely to respond, and to explore alternative therapeutic strategies. In this review, we will discuss the currently most active two drugs: ibrutinib and venetoclax, both of which have shown high response rates in R/R MCL. We review current understanding of genomic alterations associated with resistance, and discuss possible strategies to overcome these resistance mechanisms.

引用

页码：2769 / 2781

页数：13

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