Background:WhileNPM1-mutated AML in the absence ofFLT3-ITD generally carries a favorable prognosis, large registry studies suggest the positive prognostic benefit may not extend to patients > 65 years of age. We examined this preferential, age-dependent prognostic impact through a real-world analysis of 2811 adult AML patients.Results:The median overall survival (OS) was significantly better inNPM1MTcompared toNPM1WTpatients [20.86 vs. 17 mo.,p= 0.003]. When stratified by age,NPM1MTpatients had higher OS thanNPM1WTpatients in the 55–65-year age group (28.62 vs. 16.3 mo.,p≤ 0.0001). This OS benefit was heterogenous and prevailed most strikingly in the 55–60 (68.3 vs. 15.6 mo.,p= 0.002), and up to the 60–65-year group (mOS not estimable vs. 20 mo.,p= 0.007), but not beyond 65 y. Notably, the ≤65 cohort was more enriched with dominantNPM1(21% vs. 15%,p≤ 0.001), while the >65 cohort was enriched with abnormal karyotype (20% in >65 years vs. 16% in ≤65 years,p= 0.001), and co-occurringSRSF2andASXL1mutations (18.7% vs. 7.5%,p≤ 0.0001 and 13.5% vs. 4.1%,p≤ 0.0001 resp.).Conclusions:We demonstrate that in a real-world setting, the prognostic benefit ofNPM1does not extend beyond age 65, underscoring the need for age-adapted risk stratification models. This granular approach could prevent the potential overestimation of prognosis in older patients withNPM1MTAML and inform therapeutic decision making.
背景：虽然不伴有FLT3-ITD的NPM1突变急性髓系白血病通常预后良好，但大型注册研究表明这种积极的预后优势可能不适用于65岁以上患者。我们通过对2811例成人AML患者的真实世界分析，探讨了这种具有年龄选择性的预后影响差异。 结果：NPM1突变型患者的中位总生存期显著优于野生型患者（20.86个月 vs 17个月，p=0.003）。按年龄分层分析显示，在55-65岁年龄组中，NPM1突变型患者总生存期显著更长（28.62个月 vs 16.3个月，p≤0.0001）。这种生存获益呈现异质性，在55-60岁组最为显著（68.3个月 vs 15.6个月，p=0.002），并持续至60-65岁组（中位生存期无法估算 vs 20个月，p=0.007），但在65岁以上患者中未观察到显著差异。值得注意的是，≤65岁组中优势NPM1突变比例更高（21% vs 15%，p≤0.001），而>65岁组则更富集异常核型（20% vs 16%，p=0.001）以及SRSF2与ASXL1共突变（分别为18.7% vs 7.5%，p≤0.0001；13.5% vs 4.1%，p≤0.0001）。 结论：本研究在真实世界环境中证实，NPM1突变的预后优势在65岁以上患者中消失，这凸显了建立年龄适应性风险分层模型的必要性。这种精细化分析方法可避免高估老年NPM1突变AML患者的预后，并为治疗决策提供依据。
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