BTK抑制剂治疗套细胞淋巴瘤的研究进展

卜凡丹; 刘新月

doi:10.13201/j.issn.1004-2806.2016.03.025

BTK抑制剂治疗套细胞淋巴瘤的研究进展

卜凡丹,
刘新月^,

- 华中科技大学同济医学院附属协和医院血液病研究所(武汉, 430022)

详细信息

通讯作者: 刘新月,E-mail:lxy87306548@sina.com

中图分类号: R733.4

收稿日期: 2015-03-02

Research advances in treatment of mantle cell lymphoma with bruton tyrosine kinase inhibitor

BU Fandan,
LIU Xinyue^,

More Information

Corresponding author: LIU Xinyue, E-mail: lxy87306548@sina.com

Received Date: 02 March 2015

摘要

- 套细胞淋巴瘤 /
- 治疗 /
- BTK抑制剂 /
- 依鲁替尼
Abstract: Mantle cell lymphoma(MCL)is a rare,aggressive and heterogeneous clinical course of nonHodgkin's lymphoma.Although there are some promising treatment modalities,the patients always relapse early after standard immunochemotherapy regimens and develop resistance to subsequent therapies,and they generally cannot tolerate intensive approaches due to age or comorbidities.Ibrutinib is an oral active Bruton's tyrosine kinase(BTK)inhibitor.It inhibits downstream signaling pathways of BTK that appear critical for the proliferation and survival of MCL.As a single agent,it has shown extremely promising activity in relapsed and refractory MCL patients with well tolerability and acceptable toxicities,and it is likely to fundamentally change the way we treat this disease.In this paper,we will review the research advances in treatment of MCL with BTK inhibitor.
- mantle cell lymphoma /
- treatment /
- Bruton tyrosine kinase inhibitor /
- ibrutinib

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参考文献(20)

[1]	Brett LK,Williams ME.Current and emerging therapies in mantle cell lymphoma[J].Curr Treat Options Oncol,2013,14:198-211.
[2]	Honigberg LA,Smith AM,Sirisawad M,et al.The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy[J].Proc Natl Acad Sci U S A,2010,107:13075-13080.
[3]	Ponader S,Burger JA.Bruton's tyrosine kinase:from X-Linked agammaglobulinemia toward targeted therapy for B-cell malignancies[J].J Clin Oncol,2014,32:1830-1839.
[4]	Mohamed AJ,Yu L,Backesjo CM,et al.Bruton's tyrosine kinase (Btk):function,regulation,and transformation with special emphasis on the PH domain[J].Immunol Rev,2009,228:58-73.
[5]	Niemann CU,Wiestner A.B-cell receptor signaling as a driver of lymphoma development and evolution[J].Semin Cancer Biol,2013,23:410-421.
[6]	Buggy JJ,Elias L.Bruton tyrosine kinase (BTK) and its role in B-cell malignancy[J].Int Rev Immunol,2012,32:119-132.
[7]	Kil LP,de Bruijn MJ,van Nimwegen M,et al.Btk levels set the threshold for B-cell activation and negative selection of autoreactive B cells in mice[J].Blood,2012,119:3744-3756.
[8]	Cinar M,Hamedani F,Mo Z,et al.Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma and its attenuation by Ibrutinib induces apoptosis[J].Leuk Res,2013,37:1271-1277.
[9]	Chang BY,Francesco M,De Rooij MF,et al.Egress of CD19(+) CD5(+) cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients[J].Blood,2013,122:2412-2424.
[10]	Bernard S,Danglade D,Gardano L,et al.Inhibitors of BCR signalling interrupt the survival signal mediated by the micro-environment in mantle cell lymphoma[J].Int J Cancer,2015,136:2761-2774.
[11]	Advani RH,Buggy JJ,Sharman JP,et al.Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies[J].J Clin Oncol,2013,31:88-94.
[12]	Cameron F,Sanford M.Ibrutinib:first global approval[J].Drugs,2014,74:263-271.
[13]	Wang ML,Rule S,Martin P,et al.Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma[J].N Engl J Med,2013,369:507-516.
[14]	Blum KA,Christian B,Flynn J,et al.A phase I trial of the Bruton's tyrosine kinase (BTK) inhibitor,ibrutinib (PCI-32765),in combination with rituximab (R) and bendamustine in patients with relapsed/refractory non-Hodgkin's lymphoma[J].Am Soc Hematol,2012,21:abstract 1643.
[15]	Rummel MJ,Niederle N,Maschmeyer G,et al.Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas:an open-label,multicentre,randomised,phase 3 non-inferiority trial[J].Lancet,2013,381:1203-1210.
[16]	Maddocks K,Christian B,Jaglowski S,et al.A phase 1/1b study of combined rituximab,bendamustine,and ibrutinib in patients with previously untreated and relapsed/refractory non-Hodgkin's lymphoma[J].Blood,2015,125:242-248.
[17]	Younes A,Thieblemont C,Morschhauser F,et al.Combination of ibrutinib with rituximab,cyclophosphamide,doxorubicin,vincristine,and prednisone (R-CHOP) for treatment-naive patients with CD20-positive B-cell non-Hodgkin lymphoma:a non-randomised,phase 1b study[J].Lancet Oncol,2014,15:1019-1026.
[18]	Shah N,Hutchinson C,Rule S,et al.Ibrutinib for the treatment of mantle cell lymphoma[J].Expert Rev Hematol,2014,7:521-531.
[19]	Rule S,Shah N,Salles G,et al.A phase I study of the oral Btk inhibitor ONO-4059 in patients with relapsed/refractory B-cell lymphoma[J].Blood,2013,122:abstract 4397.
[20]	Evans EK,Tester R,Aslanian S,et al.Inhibition of Btk with CC-292 provides early pharmacodynamic assessment of activity in mice and humans[J].J Pharmacol Exp Ther,2013,346:219-228.