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2025-01-14T15:09:41.000Z

ELN 2024 recommendations: Genetic risk stratification in patients with AML receiving less-intensive therapies

Jan 14, 2025
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Learning objective: After reading this article, learners will be able to cite a new clinical development in acute myeloid leukemia.

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The 2017 and 2022 ELN risk classifications for patients with AML were not adequately validated in patients treated with less-intensive therapies. A new ELN 2024 genetic risk classification for stratifying prognostic outcomes in these patients was published by Dohner et al. in Blood.1


Key learnings
Patients in the favorable-risk category with IDH-mutant AML receiving AZA + IVO had a median OS of >24 months, while those in the adverse-risk category with TP53 mutation had a median OS of 5–8 months.
TP53 mutations were consistently associated with unfavorable outcomes following treatment with HMA or HMA + VEN combination. DDX41 mutations were related to favorable outcomes following both HMA monotherapy and VEN-based combination therapies. 
Patients with AML and MR mutations responded to HMA and VEN therapy; MR mutations in the presence of signaling gene mutations were associated with inferior prognosis.
The ELN 2024 recommendations on genetic risk stratification can help guide treatment in patients with AML receiving less-intensive therapies. However, further validation in clinical trials and real-world studies is needed.

Abbreviations: AML, acute myeloid leukemia; AZA, azacitidine; DDX41, DEAD-box helicase 41; ELN, European LeukemiaNet; HMA, hypomethylating agent; IDH, isocitrate dehydrogenase; IVO, ivosidenib; MR, myelodysplasia-related; OS, overall survival; TP53, tumor protein p53; VEN, venetoclax. 

  1. Döhner H, DiNardo CD, Appelbaum FR, et al. Genetic risk classification for adults with AML receiving less-intensive therapies: the 2024 ELN recommendations. Blood. 2024;144(21):2169-2173. DOI: 10.1182/blood.2024025409

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