Comprehensive Age-Stratified Impact of Mutation in Acute Myeloid Leukemia: A Real-World Experience.

While -mutated AML in the absence of -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. The median overall survival (OS) was significantly better in compared to patients [20.86 vs. 17 mo., = 0.003]. When stratified by age, patients had higher OS than patients in the 55-65-year age group (28.62 vs. 16.3 mo., ≤ 0.0001). This OS benefit was heterogenous and prevailed most strikingly in the 55-60 (68.3 vs. 15.6 mo., = 0.002), and up to the 60-65-year group (mOS not estimable vs. 20 mo., = 0.007), but not beyond 65 y. Notably, the ≤65 cohort was more enriched with dominant (21% vs. 15%, ≤ 0.001), while the >65 cohort was enriched with abnormal karyotype (20% in >65 years vs. 16% in ≤65 years, = 0.001), and co-occurring and mutations (18.7% vs. 7.5%, ≤ 0.0001 and 13.5% vs. 4.1%, ≤ 0.0001 resp.). We demonstrate that in a real-world setting, the prognostic benefit of does 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 with AML and inform therapeutic decision making.