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）抑制剂吉瑞替尼适用于复发或难治性（R/R）FLT3突变急性髓系白血病（AML），这是基于其相较于挽救性化疗（SC）所观察到的更优缓解和生存结局。在R/R AML治疗中，一线使用FLT3酪氨酸激酶抑制剂（TKIs）米哚妥林和索拉非尼可能导致对吉瑞替尼单药治疗的交叉耐药，但这一现象尚未得到充分表征。为阐明既往TKI使用的潜在临床影响，我们回顾性比较了CHRYSALIS和ADMIRAL试验中接受过米哚妥林或索拉非尼治疗的R/R FLT3突变AML患者与未接受过FLT3 TKI治疗患者的临床结局。在吉瑞替尼治疗前接受过FLT3 TKI治疗的患者（CHRYSALIS试验：42%；ADMIRAL试验：52%）与未接受过FLT3 TKI治疗的患者（CHRYSALIS试验：43%；ADMIRAL试验：55%）中观察到相似的复合完全缓解（CRc）率。在ADMIRAL试验中接受过FLT3 TKI治疗的患者中，吉瑞替尼组的CRc率更高（52%），且中位总生存期呈延长趋势，而挽救性化疗组的CRc率为20%，中位总生存期为5.1个月（风险比=0.602；95%置信区间：0.299, 1.210）。然而，既往接受过FLT3 TKI治疗的患者缓解持续时间较短。这些研究结果支持在既往使用索拉非尼或米哚妥林治疗后，将吉瑞替尼用于FLT3突变R/R AML的治疗。
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