靶向酪氨酸激酶小分子抑制剂伊布替尼的临床研究进展

Clinical research progress of ibrutinib: a small-molecule tyrosine kinase inhibitor

伊布替尼(ibrutinib,商品名Imbruvica)属于小分子布鲁顿酪氨酸激酶抑制剂,可靶向多种信号通路对肿瘤发生产生抑制、诱导以及调节免疫等作用,尤其适用于与B细胞相关的血液系统恶性肿瘤和自身免疫性疾病。FDA采用加快审评的途径批准其上市,已被用于套细胞淋巴瘤(mantle cell lymphoma,MCL)、慢性淋巴细胞白血病(chronic lymphocytic leukemia,CLL)、小淋巴细胞淋巴瘤(small lymphocytic lymphoma,SLL)、华氏巨球蛋白血症(Waldenstrm’s macroglobulinaemia,WM)、边缘区淋巴瘤(marginal zone lymphoma,MZL)以及慢性移植物抗宿主病(chronic graft-versus-host disease,cGVHD)等相关疾病的治疗,现在针对伊布替尼适应证的扩展研究仍在进行。本文从伊布替尼的研发历程、机制、药效、药动学、临床适应证、安全性等方面进行综述,为其临床研究和用药提供指导。

Ibrutinib(trade name:Imbruvica)is a potent covalent small-molecule inhibitor of Bruton’s tyrosine kinase(BTK),which effectively targets multiple signaling pathways and produces the effects of inhibition,induction and immunomodulation on tumorigenesis.It is particularly suitable for the haematopoietic malignancies and autoimmune diseases related to B lymphocytes.Ibrutinib was granted an accelerated approval by FDA for the treatment of patients with mantle cell lymphoma(MCL),chronic lymphocytic leukemia(CLL),small lymphocytic lymphoma(SLL),Waldenstrom’s macroglobulinaemia(WM),marginal zone lymphoma(MZL)and chronic graftversus-host disease(cGVHD).This article summarized the development history,mechanism,pharmacokinetics,pharmacodynamics,clinical indications and safety of ibrutinib,aiming at providing guidance for its clinical research and medication.