Therapeutic landscape and clinical management framework of FLT3 mutated acute myeloid leukemia
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摘要: 约30%的新诊断急性髓系白血病(AML)患者携带FMS样受体酪氨酸激酶3(FLT3)基因突变，大多数FLT3突变是近膜结构域内的内部串联重复(ITD)，也有少数是酪氨酸激酶结构域(TKD)内的点突变。FLT3抑制剂的应用改变了FLT3突变AML患者的治疗现状与预后。文章就FLT3突变AML的生物学特征，FLT3突变检测与诊断、FLT3抑制剂的应用及异基因造血干细胞移植中的作用等全程管理进行讨论。Abstract: Approximately 30% newly diagnosed acute myeloid leukemia(AML) patients carry mutated FMS-like tyrosine kinase 3(FLT3). Most FLT3 mutations are internal duplication(ITD) of the juxtamembrane domain, and some others are point mutations of the tyrosine kinase domain(TKD). The application of FLT3 inhibitors has dramatically improved the management and prognosis of FLT3-mutated AML. In this article, we discussed the therapeutic landscape and clinical management framework of FLT3 mutated AML, including the biological characteristics of FLT3-mutated AML, the detection and diagnosis of FLT3 mutation, and the application of FLT3 inhibitors and allogeneic hematopoietic stem cell transplantation.
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Key words:
- acute myeloid leukemia /
- FLT3 mutation
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表 1 临床批准的FLT3抑制剂
FLT3 抑制剂 代/型 适用人群 研究 临床证据 米哚妥林 Midostaurin 1/Ⅰ 新诊断FLT3突变AML与化疗联合 RATIFY研究
(NCT00651261)FDA批准，2017 索拉非尼 Sorafenib 1/Ⅱ 难治复发FLT3-ITD AML联合AZA Phase Ⅱ(NCT01254890)
Phase Ⅱ(NCT02196857)NCCN，2019 吉瑞替尼 Gilterinitib 2/Ⅰ 难治复发FLT3-ITD AML ADMIRAL研究
(NCT02421939)FDA批准，2018
中国批准，2021奎扎替尼 Quizartinib 2/Ⅱ 难治复发FLT3-ITD AML QuANTUM-R研究
(NCT02039726)日本获批，2019 
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