Approximately 30% of patients with newly diagnosed acute myeloid leukemia (AML) harbor mutations in the fms-like tyrosine kinase 3 (FLT3) gene. While the adverse prognostic impact of FLT3-ITD^mut in AML has been clearly proven, the prognostic significance of FLT3-TKD^mut remains speculative. Current guidelines recommend rapid molecular testing for FLT3^mut at diagnosis and earlier incorporation of targeted agents to achieve deeper remissions and early consideration for allogeneic stem cell transplant (ASCT). Mounting evidence suggests that FLT3^mut can emerge at any timepoint in the disease spectrum emphasizing the need for repetitive mutational testing not only at diagnosis but also at each relapse. The approval of multi-kinase FLT3 inhibitor (FLT3i) midostaurin with induction therapy for newly diagnosed FLT3^mut AML, and a more specific, potent FLT3i, gilteritinib as monotherapy for relapsed/refractory (R/R) FLT3^mut AML have improved outcomes in patients with FLT3^mut AML. Nevertheless, the short duration of remission with single-agent FLT3i’s in R/R FLT3^mut AML in the absence of ASCT, limited options in patients refractory to gilteritinib therapy, and diverse primary and secondary mechanisms of resistance to different FLT3i’s remain ongoing challenges that compel the development and rapid implementation of multi-agent combinatorial or sequential therapies for FLT3^mut AML.

大约 30% 新诊断的急性髓系白血病 (AML) 患者存在 fms 样酪氨酸激酶 3 ( FLT3 ) 基因突变。虽然FLT3 -ITD^突变对 AML 的不良预后影响已得到明确证明，但FLT3 -TKD^突变的预后意义仍然是推测性的。目前的指南建议在诊断时对FLT3^突变进行快速分子检测，并尽早加入靶向药物以实现更深程度的缓解，并尽早考虑同种异体干细胞移植 (ASCT)。越来越多的证据表明， FLT3 ^mut可以在疾病谱的任何时间点出现，这强调了不仅在诊断时而且在每次复发时都需要重复突变测试。多激酶 FLT3 抑制剂 (FLT3i) 米多妥林联合诱导治疗新诊断的FLT3^突变AML 的批准，以及更特异、有效的 FLT3i 吉尔特替尼 (gilteritinib) 作为复发/难治性 (R/R) FLT3^突变AML 的单一疗法，改善了患者的预后带有FLT3 ^mut AML。然而，在没有 ASCT 的情况下，单药 FLT3i 在 R/R FLT3 ^mut AML 中的缓解持续时间短、对 gilteritinib 治疗难治的患者的选择有限，以及对不同 FLT3i 的不同主要和次要耐药机制仍然是持续的挑战，迫使针对FLT3 ^mut AML 的多药组合或序贯疗法的开发和快速实施。