欧洲白血病网 (ELN) 急性髓系白血病 (AML) 遗传风险分类系统基于对强化化疗的反应；他们区分接受维奈托克-阿扎胞苷治疗的老年患者的结果的能力可能不是最佳的。在此，对 3 期 VIALE-A 试验 (NCT02993523) 和 1b 期研究 (NCT02203773) 中的患者进行汇总分析，根据 2017 年和 2022 年 ELN 风险分类检查预后分层。生物信息学算法得出新的分子特征，根据中位总生存期 (OS) 区分维奈托克-阿扎胞苷治疗的患者。对 279 名接受维奈托克-阿扎胞苷治疗的患者和 113 名接受安慰剂-阿扎胞苷治疗的患者进行了分析。根据 ELN 2017 或 2022 预后标准分类时，大多数患者患有不良风险 AML（维奈托克-阿扎胞苷组分别为 60.2% 和 72.8%，安慰剂-阿扎胞苷组分别为 65.5% 和 75.2%）。虽然与安慰剂阿扎胞苷相比，所有 ELN 风险组的维奈托克 - 阿扎胞苷的结局均有所改善，但 ELN 分类系统对维奈托克 - 阿扎胞苷结局的区分效果较差。通过应用生物信息学算法，得出了新的分子特征，以区分维奈托克-阿扎胞苷的 OS 结果； TP53、FLT3-ITD、NRAS 和 KRAS 的突变状态将患者分为高受益组、中受益组和低受益组（分别占患者的 52%、25% 和 23%），每个组与不同的中位值相关OS（分别为 26.5 个月 [95% CI，20.2 至 32.7]、12.1 个月 [95% CI，7.3 至 15.2] 和 5.5 个月 [95% CI，2.8 至 7.6]）。 ELN 预后分类器无法为接受维奈托克-阿扎胞苷治疗的 AML 患者提供具有临床意义的 OS 结果风险分层。 TP53、FLT3-ITD、NRAS 和 KRAS 突变状态允许将这些患者分为三个风险组，中位 OS 存在明显差异。版权所有 © 2024 美国血液学会。

European LeukemiaNet (ELN) acute myeloid leukemia (AML) genetic risk classification systems were based on response to intensive chemotherapy; their ability to discriminate outcomes in older patients treated with venetoclax-azacitidine may be suboptimal. Here, pooled analysis of patients in the phase 3 VIALE-A trial (NCT02993523) and phase 1b study (NCT02203773) examined prognostic stratification according to 2017 and 2022 ELN risk classifications. A bioinformatic algorithm derived new molecular signatures differentiating venetoclax-azacitidine-treated patients based on median overall survival (OS). 279 patients treated with venetoclax-azacitidine and 113 patients treated with placebo-azacitidine were analyzed. When classified by ELN 2017 or 2022 prognostic criteria, most patients had adverse-risk AML (60.2% and 72.8% for venetoclax-azacitidine and 65.5% and 75.2% for placebo-azacitidine, respectively). While outcomes with venetoclax-azacitidine were improved across all ELN risk groups compared with placebo-azacitidine, ELN classification systems poorly discriminated venetoclax-azacitidine outcomes. By applying a bioinformatic algorithm, new molecular signatures were derived differentiating OS outcomes with venetoclax-azacitidine; the mutational status of TP53, FLT3-ITD, NRAS, and KRAS categorized patients into higher-, intermediate-, and lower-benefit groups (52%, 25%, and 23% of patients, respectively), each associated with a distinct median OS (26.5 months [95% CI, 20.2 to 32.7], 12.1 months [95% CI, 7.3 to 15.2], and 5.5 months [95% CI, 2.8 to 7.6], respectively). ELN prognostic classifiers do not provide clinically meaningful risk stratification of OS outcomes for patients with AML treated with venetoclax-azacitidine. TP53, FLT3-ITD, NRAS, and KRAS mutation status allows classification of these patients into three risk groups with distinct differences in median OS.Copyright © 2024 American Society of Hematology.