Tran Phu N, O'Brien Susan
a Division of Hematology-Oncology , University of California Irvine , Orange , CA , USA.
Expert Opin Drug Saf. 2017 Sep;16(9):1079-1088. doi: 10.1080/14740338.2017.1344213. Epub 2017 Jun 23.
The approval of ibrutinib has revolutionized the therapeutic landscape of chronic lymphocytic leukemia (CLL). Currently ibrutinib is indicated for patients that are both treatment naïve as well as those with relapsed CLL. Ibrutinib is generally well-tolerated with durable responses that improve over time in most patients. Important toxicities include atrial fibrillation and bleeding. Areas cover: This review covers the pharmacokinetics, pharmacodynamics, safety and efficacy of ibrutinib in the treatment of CLL. We also compare ibrutinib with other kinase inhibitors and chemoimmunotherapy regimens using data from clinical trials. A literature search utilized the PubMed database. Expert opinion: Despite the efficacy and tolerability of ibrutinib, important questions remain, which include selection of patients receiving ibrutinib in the first and subsequent lines of treatment, optimal dosing, sequential use of ibrutinib versus other kinase inhibitors and combination therapy. Prospective studies should incorporate minimal residual disease (MRD) status as a clinical endpoint to determine whether patients can be taken off kinase inhibitors.
依鲁替尼的获批彻底改变了慢性淋巴细胞白血病(CLL)的治疗格局。目前,依鲁替尼适用于初治患者以及复发的CLL患者。依鲁替尼一般耐受性良好,多数患者的持久反应会随时间改善。重要的毒性反应包括心房颤动和出血。涵盖领域:本综述涵盖依鲁替尼治疗CLL的药代动力学、药效学、安全性和疗效。我们还利用临床试验数据将依鲁替尼与其他激酶抑制剂及化疗免疫治疗方案进行比较。文献检索使用了PubMed数据库。专家意见:尽管依鲁替尼具有疗效和耐受性,但仍存在重要问题,包括一线及后续治疗中接受依鲁替尼治疗的患者选择、最佳剂量、依鲁替尼与其他激酶抑制剂的序贯使用以及联合治疗。前瞻性研究应将微小残留病(MRD)状态纳入临床终点,以确定患者是否可以停用激酶抑制剂。