University of California San Francisco, 505 Parnassus Ave, San Francisco, CA, 94143, USA.
Clin Lymphoma Myeloma Leuk. 2020 Sep;20 Suppl 1:S5-S6. doi: 10.1016/S2152-2650(20)30441-9.
Mutations in the FLT3 receptor tyrosine kinase are the most frequently found mutations in acute myeloid leukemia (AML). Patients with FLT3 internal tandem duplication (ITD) mutations have poor prognoses. The approved FLT3 tyrosine kinase inhibitors (TKIs) midostaurin and gilteritinib improve survival in AML with FLT3 mutations. Multiple other FLT3 inhibitors are in clinical development. Patients frequently relapse after response to FLT3 inhibitors and the optimal use of FLT3 inhibitors in the upfront, relapse, and maintenance settings remain to be established. We will discuss the biology of FLT3, approved and investigational FLT3 inhibitors, resistance mechanisms, and emerging FLT3 TKI combination clinical trials.
FLT3 受体酪氨酸激酶突变是急性髓系白血病（AML）中最常见的突变。FLT3 内部串联重复（ITD）突变的患者预后不良。已批准的 FLT3 酪氨酸激酶抑制剂（TKIs）米哚妥林和吉特替尼可改善伴有 FLT3 突变的 AML 的生存率。还有多种其他的 FLT3 抑制剂正在临床开发中。患者在对 FLT3 抑制剂有反应后经常复发，并且在一线、复发和维持治疗中最佳使用 FLT3 抑制剂仍有待确定。我们将讨论 FLT3 的生物学、已批准和研究中的 FLT3 抑制剂、耐药机制以及新兴的 FLT3 TKI 联合临床试验。
