The fms-like tyrosine kinase 3 (FLT3) inhibitor gilteritinib is indicated for relapsed or refractory (R/R) FLT3-mutated acute myeloid leukemia (AML), based on its observed superior response and survival outcomes compared with salvage chemotherapy (SC). Frontline use of FLT3 tyrosine kinase inhibitors (TKIs) midostaurin and sorafenib may contribute to cross-resistance to single-agent gilteritinib in the R/R AML setting but has not been well characterized. To clarify the potential clinical impact of prior TKI use, we retrospectively compared clinical outcomes in patients with R/R FLT3-mutated AML in the CHRYSALIS and ADMIRAL trials who received prior midostaurin or sorafenib against those without prior FLT3 TKI exposure. Similarly high rates of composite complete remission (CRc) were observed in patients who received a FLT3 TKI before gilteritinib (CHRYSALIS, 42%; ADMIRAL, 52%) and those without prior FLT3 TKI therapy (CHRYSALIS, 43%; ADMIRAL, 55%). Among patients who received a prior FLT3 TKI in ADMIRAL, a higher CRc rate (52%) and trend toward longer median overall survival was observed in the gilteritinib arm versus the SC arm (CRc = 20%; overall survival, 5.1 months; HR = 0.602; 95% CI: 0.299, 1.210). Remission duration was shorter with prior FLT3 TKI exposure. These findings support gilteritinib for FLT3-mutated R/R AML after prior sorafenib or midostaurin.

fms样酪氨酸激酶 3 ( FLT3) 抑制剂 gilteritinib 适用于复发性或难治性 (R/R) FLT3突变的急性髓细胞性白血病 (AML)，基于其观察到的与挽救性化疗 (SC) 相比具有更好的反应和生存结果。一线使用 FLT3 酪氨酸激酶抑制剂 (TKI) midostaurin 和索拉非尼可能导致 R/R AML 环境中对单药 gilteritinib 的交叉耐药性，但尚未得到很好的表征。为了阐明先前使用 TKI 的潜在临床影响，我们回顾性比较了 R/R FLT3-在 CHRYSALIS 和 ADMIRAL 试验中，先前接受过米多司林或索拉非尼的试验中发生突变的 AML 与先前未接触过 FLT3 TKI 的患者相比。在 gilteritinib 之前接受 FLT3 TKI 的患者（CHRYSALIS，42%；ADMIRAL，52%）和未接受 FLT3 TKI 治疗的患者（CHRYSALIS，43%；ADMIRAL，55%）观察到类似的高复合完全缓解率 (CRc) . 在 ADMIRAL 接受过 FLT3 TKI 的患者中，gilteritinib 组与 SC 组相比，观察到更高的 CRc 率（52%）和更长的中位总生存期趋势（CRc = 20%；总生存期，5.1 个月；HR = 0.602；95% CI：0.299, 1.210)。先前 FLT3 TKI 暴露的缓解持续时间较短。这些发现支持在先前的索拉非尼或米多司他林之后使用 gilteritinib 治疗FLT3突变的R/R AML。