Loschi Michael, Sammut Rinzine, Chiche Edmond, Cluzeau Thomas
Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Nice, 06200 Nice, France.
Université Cote d'Azur, 06108 Nice, France.
Int J Mol Sci. 2021 May 30;22(11):5873. doi: 10.3390/ijms22115873.
FLT3-mutated acute myeloid leukemia accounts for around 30% of acute myeloid leukemia (AML). The mutation carried a poor prognosis until the rise of tyrosine kinase inhibitors (TKIs). New potent and specific inhibitors have successfully altered the course of the disease, increasing the complete response rate and the survival of patients with FLT3-mutated AML. The aim of this article is to review all the current knowledge on these game-changing drugs as well as the unsolved issues raised by their use for fit and unfit FLT3-mutated AML patients. To this end, we analyzed the results of phase I, II, III clinical trials evaluating FLT3-TKI both in the first-line, relapse monotherapy or in combination referenced in the PubMed, the American Society of Hematology, the European Hematology Association, and the Clinicaltrials.gov databases, as well as basic science reports on TKI resistance from the same databases. The review follows a chronological presentation of the different trials that allowed the development of first- and second-generation TKI and ends with a review of the current lines of evidence on leukemic blasts resistance mechanisms that allow them to escape TKI.
FLT3 突变的急性髓系白血病约占急性髓系白血病（AML）的 30%。在酪氨酸激酶抑制剂（TKIs）出现之前，这种突变预后较差。新型强效特异性抑制剂成功改变了疾病进程，提高了 FLT3 突变 AML 患者的完全缓解率和生存率。本文旨在综述关于这些改变游戏规则的药物的所有现有知识，以及其用于适合和不适合的 FLT3 突变 AML 患者所引发的未解决问题。为此，我们分析了在 PubMed、美国血液学会、欧洲血液学协会和 Clinicaltrials.gov 数据库中引用的评估 FLT3-TKI 在一线、复发单药治疗或联合治疗中的 I、II、III 期临床试验结果，以及来自同一数据库的关于 TKI 耐药性的基础科学报告。该综述按时间顺序呈现了不同的试验，这些试验促成了第一代和第二代 TKI 的研发，最后综述了关于白血病原始细胞耐药机制的当前证据线索，正是这些机制使它们能够逃避 TKI 的作用。
