FLT3基因是急性髓系白血病（AML）中最常发生突变的基因，其中FLT3内部串联复制（ITD）突变与更具侵袭性的临床进程相关。尽管两项大型随机临床试验表明，口服FLT3抑制剂（米多吡啶或奎扎替尼）在具有FLT3突变的AML患者中的一线使用可以提高生存率，但在新诊断的、具有FLT3突变的AML的老年患者中，FLT3抑制剂的作用尚不清楚。在60岁及以上的受过强化治疗的患者中，一线使用FLT3抑制剂并没有观察到明确的生存改善。此外，由于年龄和/或合并症，许多具有FLT3突变的AML患者不适合强化化疗，这一人群有特殊的未满足需求。对于这些对强化治疗不适用的老年患者，azacitidine + 韦奴托可西酮已成为新的标准治疗，并且无论FLT3突变状况如何，许多临床医生都在使用该疗法。然而，FLT3-ITD突变导致对韦奴托可西酮的耐药性，并且是降低强度韦奴托可西酮为基础的治疗方案复发的确定机制，导致缓解期短且生存率差。前临床和临床数据表明，FLT3抑制剂和韦奴托可西酮之间存在协同作用，为它们的联合使用提供了理论基础。现在，正在研究将FLT3抑制剂安全地纳入常规的甲基化剂+韦奴托可西酮骨架中，用于新诊断的、具有FLT3突变的AML的老年、较不适合的患者，并取得了令人鼓舞的早期结果。本文讨论了在新诊断的具有FLT3突变的AML的老年患者中，一线使用FLT3抑制剂的情况，包括FLT3抑制剂与强化化疗的联合使用可能以及在这一老年人群中作为新型、较低强度双联和三联治疗方案的潜在作用。©2023 Springer Nature Limited.

FLT3 is the most frequently mutated gene in acute myeloid leukemia (AML), with FLT3 internal tandem duplication (ITD) mutations being associated with a more aggressive clinical course. While two large, randomized clinical trials have shown a survival benefit with the frontline use of an oral FLT3 inhibitor (midostaurin or quizartinib) in patients with FLT3-mutated AML, the role of FLT3 inhibitors in older adults with newly diagnosed FLT3-mutated AML remains unclear. A definitive improvement in survival has not been observed in intensively treated patients over 60 years of age receiving frontline FLT3 inhibitors. Furthermore, many patients with FLT3-mutated AML are unsuitable for intensive chemotherapy due to age and/or comorbidities, and this population represents a particular unmet need. For these older patients who are unfit for intensive approaches, azacitidine + venetoclax is a new standard of care and is used by many clinicians irrespective of FLT3 mutation status. However, FLT3-ITD mutations confer resistance to venetoclax and are a well-established mechanism of relapse to lower-intensity venetoclax-based regimens, leading to short durations of remission and poor survival. Preclinical and clinical data suggest synergy between FLT3 inhibitors and venetoclax, providing rationale for their combination. Novel strategies to safely incorporate FLT3 inhibitors into the standard hypomethylating agent + venetoclax backbone are now being explored in this older, less fit population with newly diagnosed FLT3-mutated AML, with encouraging early results. Herein, we discuss the frontline use of FLT3 inhibitors in older adults with FLT3-mutated AML, including the potential role of FLT3 inhibitors in combination with intensive chemotherapy and as part of novel, lower-intensity doublet and triplet regimens in this older population.© 2023. Springer Nature Limited.