Hospital de la Santa Creu i Sant Pau. Institut d'investigació Biomèdica Sant Pau (IIB SANT PAU) Department of Medicine, Universitat Autonoma of Barcelona, Barcelona, Spain.
Hospital Clinic. August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain.
Blood Cancer J. 2023 May 5;13(1):69. doi: 10.1038/s41408-023-00839-1.
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.
米哚妥林联合强化化疗是 FLT3 突变（FLT3mut）急性髓系白血病（AML）的标准治疗方法。我们分析了米哚妥林对 227 例纳入 AML-12 前瞻性试验的适合年龄≤70 岁的 FLT3mut-AML 患者（#NCT04687098）的影响。患者分为早期（2012-2015 年）和晚期（2016-2020 年）两组。两组患者均采用相同的治疗方案，除晚期组 71%的患者加用米哚妥林外。两组之间的反应率或异基因移植的数量没有差异。晚期组的结果有所改善：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）从早期组的 47%提高至晚期组的 61%（p=0.042）。米哚妥林的疗效在 NPM1mut 患者（n=151）中得到证实，2 年 OS 分别为暴露组 72%和未暴露组 50%（p=0.011），并减轻了 FLT3-ITD 等位基因比例的预后价值：米哚妥林组 2 年 OS 在低比值和高比值患者中分别为 85%和 58%（p=0.049），在未暴露组中分别为 67%和 39%（p=0.005）。在野生型 NPM1 亚组（n=75）中，我们没有观察到两个研究时期之间的显著差异。总之，这项研究强调了纳入米哚妥林后，FLT3mut AML 适合患者的预后得到改善。
