Yosef Amir, Touloukian Emily Z, Nambudiri Vinod E
1 Grand Strand Regional Medical Center, Myrtle Beach, USA.
2 Coastal Cancer Center, Myrtle Beach, USA.
J Oncol Pharm Pract. 2019 Mar;25(2):434-441. doi: 10.1177/1078155218786037. Epub 2018 Jul 12.
Bruton tyrosine kinase plays a critical role in hastening cell proliferation. Bruton tyrosine kinase inhibitors are a class of immunotheraputic agents that disrupt this signaling pathway. Ibrutinib, a novel Bruton tyrosine kinase inhibitor approved by the Food and Drug Administration (FDA) for the treatment of Waldenstrom macroglobulinemia in patients who have failed treatment with other agents, has emerged as an important therapeutic agent in the management of Waldenstrom macroglobulinemia and other plasma cell dyscrasias. Ibrutinib has shown to increase progression free survival and improve overall mortality. We present a review of ibrutinib, beginning with an overview of the Bruton tyrosine kinase pathway and clinically relevant gene mutations impacting treatment and prognosis for patients with Waldenstrom macroglobulinemia, followed by evidence supporting therapeutic indications for ibrutinib, and detailing its safety and efficacy evidence, current clinical guidelines, adverse effects and their management, and finally challenges of drug resistance. We also present findings on newly developed Bruton tyrosine kinase inhibitors in the therapeutic pipeline to provide readers insight into this rapidly evolving corner of oncology pharmacy practice.
布鲁顿酪氨酸激酶在加速细胞增殖中起关键作用。布鲁顿酪氨酸激酶抑制剂是一类破坏该信号通路的免疫治疗药物。依鲁替尼是一种新型布鲁顿酪氨酸激酶抑制剂，已获美国食品药品监督管理局（FDA）批准，用于治疗经其他药物治疗无效的华氏巨球蛋白血症患者，它已成为治疗华氏巨球蛋白血症和其他浆细胞发育异常的重要治疗药物。依鲁替尼已显示可提高无进展生存期并改善总体死亡率。我们对依鲁替尼进行综述，首先概述布鲁顿酪氨酸激酶途径以及影响华氏巨球蛋白血症患者治疗和预后的临床相关基因突变，接着阐述支持依鲁替尼治疗指征的证据，并详细说明其安全性和有效性证据、当前临床指南、不良反应及其管理，最后介绍耐药性挑战。我们还展示了处于治疗研发阶段的新开发布鲁顿酪氨酸激酶抑制剂的研究结果，以使读者深入了解肿瘤药学实践中这个快速发展的领域。
