新型Bruton酪氨酸激酶抑制剂在B细胞淋巴瘤中的应用进展  

Topic Review Application progress of novel Bruton tyrosine kinase inhibitors in B-cell lymphoma

作　　者：赵东陆[1] 马军[1] Zhao Donglu;Ma Jun(Harbin Institute of Hematology and Oncology,Harbin 150010,China)

机构地区：[1]哈尔滨血液病肿瘤研究所,150010

出　　处：《白血病．淋巴瘤》2020年第2期79-82,共4页Journal of Leukemia & Lymphoma

摘　　要：Bruton酪氨酸激酶(BTK)抑制剂伊布替尼在B细胞淋巴瘤治疗中获得了卓越的效果,但在临床上仍不能满足治疗需求。新型BTK抑制剂具有高度选择性和特异性,减少了脱靶效应。阿卡替尼联合其他药物疗法总有效率(ORR)超过90%,并且外周血和骨髓微小残留病(MRD)阴性率很高。对我国研制的新型的BTK抑制剂奥布替尼进行的多中心Ⅱ期研究结果显示,奥布替尼治疗复发难治慢性淋巴细胞白血病/小细胞淋巴瘤的ORR为88.5%,治疗套细胞淋巴瘤的ORR为82.5%。国际多中心对另一个新型BTK抑制剂泽布替尼进行研究的结果显示,泽布替尼在复发难治慢性淋巴细胞白血病患者中的ORR为95.9%,在有del(17p)初治慢性淋巴细胞白血病(CLL)患者中的ORR为92.2%。另外,非共价BTK抑制剂也崭露头角,有望克服BTK抑制剂耐药的问题。The Bruton tyrosine kinase(BTK)inhibitor ibrtinib has excellent results in B-cell lymphoma.However,there are still unmet treatment needs in clinical practice.New BTK inhibitors are highly selective and specific,reducing off-target effects.The overall response rate(ORR)of acalabrutinib combination therapy is more than 90%,and high rates of peripheral blood and bone marrow minimal residual disease(MRD)-negative are obtained.Orelabrutinib is a new domestic BTK inhibitor,the results of a phaseⅡstudy showed that the ORR in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma is 88.5%,and in mantle cell lymphoma is 82.5%.Another new domestic BTK inhibitor zanubrutinib,international multi-center study showed that ORR is 95.9%in relapsed/refractory CLL,and in treatment-na?ve chronic lymphocytic leukemia with del(17p)is 92.2%.In addition,non-covalent BTK inhibitors are also emerging,which are expected to overcome the problem of resistance to BTK inhibitors.

关 键 词：淋巴瘤 B细胞 蛋白酪氨酸激酶类 蛋白激酶抑制剂 Bruton酪氨酸激酶 

分 类 号：R733[医药卫生—肿瘤]