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Mutation testing in AML:
What you need to know
with Charles Craddock, Ralph Hills, and Gail Roboz
Wednesday, April 23, 2025
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ELN 2024 recommendations: Genetic risk stratification in patients with AML receiving less-intensive therapies
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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.
- 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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