Comparison and validation of the 2022 European LeukemiaNet guidelines in acute myeloid leukemia.

Risk stratification in acute myeloid leukemia (AML) remains principle for survival prognostication and treatment selection. The 2022 European LeukemiaNet (ELN) recommendations were recently published, with notable updates to risk group assignment. The complexity of risk stratification and comparative outcomes between the 2022 and 2017 ELN guidelines remains unknown. This comparative analysis evaluated outcomes between the 2017 and 2022 ELN criteria in patients enrolled within the multi-center Beat AML cohort. Five-hundred thirteen patients were included. Most patients had one (36% [N=183]) or two (31% [N=159]) ELN risk-defining abnormalities. In patients with two or more ELN-risk defining mutations (58% [N=297]), 44% (N=132) had mutations spanning multiple ELN risk categories. Compared to ELN 2017 criteria, the updated ELN 2022 guidelines changed assigned risk group in 15% (N=75) of patients, including 10% (N=16/160), 26% (N=29/112), and 6% (N=13/224) of ELN 2017 favorable, intermediate, and adverse-risk patients. Median OS across ELN 2022 favorable, intermediate, and adverse-risk groups was not reached (estimated 5-year OS: 53% [standard error: 0.06%]), 16.8 (95% CI: 11-48) and 9.7 (95% CI: 8.3-10.8) months, respectively. The ELN 2022 guidelines more accurately stratified survival between patients with intermediate or adverse-risk AML treated with IC (HR: 1.58 [95% CI: 1.12-2.25], p-value: 0.01) compared to ELN 2017 guidelines (HR 1.27 [95% CI: 0.88-1.85], p-value: 0.20). The updated ELN 2022 guidelines better stratify survival, namely between patients with intermediate or adverse-risk AML treated with IC. The increased complexity of risk stratification with inclusion of additional cytogenetic and molecular aberrations necessitates clinical workflows simplifying risk stratification.