P513: molecular pattern by age and overall survival in acute myeloid leukemia: a population-based study from the swedish aml registry.

Background: AML is mostly a disease of the elderly with a median age of 72 years, but most molecular data originate from clinical studies, usually with age restrictions. Aims: To report population-based data on mutations from the Swedish AML Registry by age and outcome. Methods: Selected gene mutations (FLT3-ITD, NPM1 and CEBPA) became possible to report to the registry in 2007. Extended gene analyses started in 2016 with whole-exome sequencing (WES) in a few research sites, and TruSight Myeloid Panel (54 genes), later exchanged for Twist (195 genes) in clinical practice, but reporting could not start until 2020. Mutation data from clinical routine were therefore retrospectively added to the registry through hospital genetic laboratory databases. Data was extracted from the Swedish AML Registry on January 3, 2023. Results: Among 6525 patients diagnosed since 2007 molecular data was available from 3326 (51%). Between 2016 and 2022 the proportion of patients with panel or WES data increased from 22% to 71%. Currently the registry contains panel/WES data from 73% of patients <65 years, 55% 65-79 years, 27% 80-84 years, and 10% 85 years, i.e., from 1579 patients with a median age of 68 years. The overall frequency of specific mutations was slightly different to other studies, probably due to the real-world age distribution. The mean number of mutations per patient was 3.4. Overall, mutations were less common in younger patients, 2.3/pat <40 yrs, 3.0 in patients 40-64 years, 3.7 in patients 65-74 yrs and 3.8 in patients 75+ years. Mutation rates were skewed by age for many genes (Figure). FLT3, CEBPA and NRAS were more frequently mutated in young patients, whereas NPM1, DNMT3A, IDH1/2, STAG2 and SRSF2 were rarely mutated in young. TET2, ASXL1 and TP53 were most frequently mutated in older. Among those with panel/WES-data, 69% received intensive, 22% hypomethylating agents, and 9% palliation only (median ages 63, 76 and 78 years, respectively). Overall survival according to molecular subtypes are shown in the Table. Summary/Conclusion: Our data show that the overall incidence of mutations increases by age up to 65 years, but thereafter remains stable, whereas certain genes have different age distributions. The strong impact of specific genetic alterations on survival in a large population-based study with real-life age distribution is shown. The clinical impact of combinations of specific mutations and karyotypes is being evaluated.Keywords: Mutation status, Age, Acute myeloid leukemia, Survival