Midostaurin added to intensive chemotherapy is the standard of care for acute myeloid leukemia (AML) with FLT3 mutations (FLT3mut). We analyzed the impact of midostaurin in 227 FLT3mut-AML patients included in the AML-12 prospective trial for fit patients ≤70 years (#NCT04687098). Patients were divided into an early (2012–2015) and late (2016–2020) cohorts. They were uniformly treated except for the addition of midostaurin in 71% of late group patients. No differences were observed in response rates or the number of allotransplants between groups. Outcome was improved in the late period: 2-year relapse incidence decreased from 42% vs 29% in early vs late group (p = 0.024) and 2-year overall survival (OS) improved from 47% vs 61% (p = 0.042), respectively. The effect of midostaurin was evident in NPM1mut patients (n = 151), with 2-yr OS of 72% (exposed) vs 50% (naive) patients (p = 0.011) and mitigated FLT3-ITD allelic ratio prognostic value: 2-yr OS with midostaurin was 85% and 58% in low and high ratio patients (p = 0.049) vs 67% and 39% in naive patients (p = 0.005). In the wild-type NPM1 subset (n = 75), we did not observe significant differences between both study periods. In conclusion, this study highlights the improved outcome of FLT3mut AML fit patients with the incorporation of midostaurin.
在强化化疗基础上联合米哚妥林（midostaurin）已成为FLT3突变（FLT3mut）急性髓系白血病（AML）的标准治疗方案。本研究分析了纳入AML-12前瞻性临床试验（编号#NCT04687098）的227例年龄≤70岁、身体状况良好的FLT3mut-AML患者数据。患者按治疗时间分为早期（2012-2015年）和晚期（2016-2020年）队列。除晚期组71%的患者加用米哚妥林外，两组治疗方案保持一致。两组间缓解率或异基因移植数量均无显著差异。晚期组患者的预后得到改善：2年复发率从早期组的42%降至晚期组的29%（p=0.024），2年总生存率（OS）从47%提升至61%（p=0.042）。米哚妥林的疗效在NPM1突变患者（n=151）中尤为显著：用药组2年OS达72%，未用药组为50%（p=0.011），且该药物削弱了FLT3-ITD等位基因比值的预后价值——用药组中低比值与高比值患者的2年OS分别为85%和58%（p=0.049），而未用药组分别为67%和39%（p=0.005）。在NPM1野生型亚组（n=75）中，两个研究时期未见显著差异。本研究证实，联合米哚妥林可改善身体状况良好的FLT3mut-AML患者的临床结局。
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