摘要
第一代Bruton酪氨酸激酶抑制剂(BTKi)伊布替尼的出现明显改善了慢性淋巴细胞白血病(CLL)患者的生存和预后,但其不良反应如出血、感染、心血管事件等限制了患者的长期使用。新一代BTKi具有更高的选择性和特异性,能明显减少患者不良反应发生。其中acalabrutinib在初治和复发难治CLL患者中的疗效和安全性已在Ⅲ期临床试验中被证实。我国自主研发的泽布替尼和奥布替尼也在临床前和Ⅰ、Ⅱ期研究中初步证明了其安全性和有效性,尚缺乏大型Ⅲ期临床试验数据。目前,更多的BTKi还处在研发阶段。未来CLL的治疗可能转变为各类药物联用达到微小残留病(MRD)阴性后停药或以MRD指导治疗等,而新一代BTKi的问世也将为这种联合治疗方案提供更好的选择。
The first-generation Bruton tyrosine kinase inhibitor(BTKi)ibrutinib significantly improved the survival and prognosis of patients with chronic lymphocytic leukemia(CLL),but its adverse reactions such as bleeding,infection,cardiovascular events,etc.,limited the long-term compliance of patients.It has been considered that the new generation of BTKi could significantly reduce the adverse reactions caused by ibrutinib because of their higher selectivity and specificity.Among them,the efficacy and safety of acalabrutinib in untreated and relapsed/refractory patients with CLL have been confirmed in phaseⅢclinical trials.In addition,zanubrutinib and orelabrutinib,which were independently developed in China,have also been proven their preliminary safety and therapeutic effects in pre-clinical and phaseⅠandⅡclinical trials,while the data from large phaseⅢclinical trials are still lacking.Currently,more BTKi are also under active exploration.The future therapeutic strategies of CLL may be converted to combining with a wide range of drugs to achieve the goal of drug discontinuation when minimal residual disease(MRD)is negative,or use MRD to guide the treatment.In this trend,the new generation of BTKi will provide more optimized options for the combination therapy regimens.
作者
黄海雯
吴德沛
Huang Haiwen;Wu Depei(Department of Hematology,the First Affiliated Hospital of Soochow University,Suzhou 215006,China)
出处
《白血病．淋巴瘤》
CAS
2020年第8期449-452,共4页
Journal of Leukemia & Lymphoma
基金
国家临床医学中心转化研究开放课题(2020ZKMB02)。
