Bhatt Valkal, Alejandro Linh, Michael Angela, Ganetsky Alex
Department of Pharmacy, Memorial Sloan-Kettering Cancer Center, New York, New York.
Pharmacotherapy. 2014 Mar;34(3):303-14. doi: 10.1002/phar.1366. Epub 2013 Dec 12.
Lymphoid malignancies comprise a heterogeneous group of disorders originating from clonal proliferation of B or T lymphocytes. Treatment of lymphoid neoplasms has traditionally been pursued with cytotoxic chemotherapy. To improve efficacy and ameliorate the adverse effects associated with classic chemotherapy, molecularly targeted therapy has been developed. At the forefront of clinical development is ibrutinib, an inhibitor of Bruton's tyrosine kinase (Btk). Btk is a protein tyrosine kinase that plays an important role in regulating B-cell signaling. Dysregulated Btk results in uncontrolled B-lymphocyte proliferation, differentiation, and survival. Ibrutinib is currently being studied in numerous malignancies of lymphoid origin including chronic lymphocytic leukemia, mantle cell lymphoma, non-Hodgkin lymphoma, follicular lymphoma, and multiple myeloma. Thus far, ibrutinib has demonstrated very promising results in treatment-naive patients as well as those with relapsed or refractory disease with an acceptable safety profile. In this article, we describe the pharmacology, efficacy, and toxicity profile of ibrutinib and depict the potential role that ibrutinib will play in the treatment paradigm of lymphoid neoplasms.
淋巴系统恶性肿瘤是一组异质性疾病,起源于B或T淋巴细胞的克隆性增殖。传统上,淋巴系统肿瘤的治疗采用细胞毒性化疗。为了提高疗效并改善与传统化疗相关的不良反应,人们开发了分子靶向治疗。处于临床开发前沿的是伊布替尼,一种布鲁顿酪氨酸激酶(Btk)抑制剂。Btk是一种蛋白酪氨酸激酶,在调节B细胞信号传导中起重要作用。Btk失调会导致B淋巴细胞不受控制地增殖、分化和存活。伊布替尼目前正在多种淋巴系统起源的恶性肿瘤中进行研究,包括慢性淋巴细胞白血病、套细胞淋巴瘤、非霍奇金淋巴瘤、滤泡性淋巴瘤和多发性骨髓瘤。到目前为止,伊布替尼在初治患者以及复发或难治性疾病患者中均显示出非常有前景的结果,且安全性可接受。在本文中,我们描述了伊布替尼的药理学、疗效和毒性特征,并阐述了伊布替尼在淋巴系统肿瘤治疗模式中可能发挥的作用。