Berman Ellin
Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical Center, New York, NY.
Blood. 2022 May 26;139(21):3138-3147. doi: 10.1182/blood.2021011722.
When imatinib, the first tyrosine kinase inhibitor (TKI) developed for use in chronic myelogenous leukemia (CML), was approved in 2001, the treatment of this disease was forever changed. Significant reductions in the molecular burden of disease were seen with the first-generation TKI imatinib and, with the addition of dasatinib (2006), nilotinib (2007), bosutinib (2012), and ponatinib (2013), deeper and more rapid reductions were noted. Physicians could begin to tailor TKI therapy to individual patients, and patients who did not respond to or could not tolerate first-line therapy now had options. Importantly, the number of patients who developed accelerated or blast phase disease decreased dramatically. Research in CML continues to evolve; by presenting illustrative cases, this article reviews some of the newer aspects of clinical care in this disease. Updated information regarding bosutinib and asciminib, the latter currently in clinical trials, will be presented; bosutinib is of particular interest as the drug's transit through the United States Food and Drug Administration highlights the question of what is considered optimal response to TKI therapy. The challenge of understanding the cardiac safety data of ponatinib and the unique dosing schedule based on individual response will be discussed. Lastly, two cases will focus on features of TKI treatment that, remarkably, have become part of the treatment algorithm: family planning for women with CML and stopping therapy after meeting a specific treatment milestone.
2001年,首个用于治疗慢性粒细胞白血病(CML)的酪氨酸激酶抑制剂(TKI)伊马替尼获批,从此这种疾病的治疗发生了翻天覆地的变化。第一代TKI伊马替尼显著降低了疾病的分子负担,随着达沙替尼(2006年)、尼洛替尼(2007年)、博舒替尼(2012年)和普纳替尼(2013年)的相继问世,疾病负担的降低更为显著且迅速。医生们开始能够根据患者个体情况定制TKI治疗方案,那些对一线治疗无反应或无法耐受的患者现在也有了更多选择。重要的是,进展为加速期或急变期疾病的患者数量大幅减少。CML的研究仍在不断发展;通过展示一些典型病例,本文回顾了该疾病临床治疗中的一些新进展。文中将介绍博舒替尼和阿西替尼(后者目前正处于临床试验阶段)的最新信息;博舒替尼尤其值得关注,因为该药在美国食品药品监督管理局的审批过程引发了关于TKI治疗最佳反应标准的讨论。还将探讨理解普纳替尼心脏安全性数据以及基于个体反应的独特给药方案所面临的挑战。最后,两个病例将聚焦于TKI治疗的一些特点,这些特点显著地已成为治疗方案的一部分:CML女性患者的计划生育以及在达到特定治疗里程碑后停止治疗。