Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN
- Study type
- Clinical guideline
- Study name
- ELN 2022 (AML)
- Design
- Recommendations of an international expert panel (consensus, based on published evidence)
- Source
- Blood · 2022
In plain words
The ELN is the most important European reference for diagnosing and treating acute myeloid leukaemia. According to this guideline, full genetic testing (including FLT3, NPM1 and several other genes) should be done at diagnosis, because the results determine both how serious the disease is (low, intermediate or high risk) and the type of treatment (for example, adding a targeted drug or the need for a bone marrow transplant). For patients who cannot tolerate intensive chemotherapy, there are also effective gentler treatments.
Key guideline recommendations
- Panel consensus (not graded)
Favourable risk group: t(8;21)(q22;q22.1)/RUNX1::RUNX1T1; inv(16)(p13.1q22) or t(16;16)(p13.1;q22)/CBFB::MYH11; mutated NPM1 without FLT3-ITD; in-frame bZIP mutation of CEBPA.
- Panel consensus (not graded)
Intermediate risk group: mutated NPM1 with FLT3-ITD; wild-type NPM1 with FLT3-ITD (without adverse-risk genetic lesions); t(9;11)(p21.3;q23.3)/MLLT3::KMT2A; and cytogenetic or molecular abnormalities not classified as favourable or adverse. In ELN 2022, the FLT3-ITD allelic ratio is no longer considered in assigning the risk group.
- Panel consensus (not graded)
Adverse risk group: t(6;9)/DEK::NUP214; KMT2A rearrangements other than MLLT3::KMT2A; t(9;22)/BCR::ABL1; inv(3) or t(3;3)/GATA2, MECOM and other MECOM rearrangements; −5 or del(5q), −7, −17/abn(17p); complex or monosomal karyotype; mutations in ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1 and/or ZRSR2; and TP53 mutation (variant allele frequency at least 10%).
- Panel consensus (not graded)
At diagnosis, genetic work-up including karyotype and molecular testing of key genes (including FLT3, NPM1, CEBPA, IDH1 and IDH2, myelodysplasia-related genes and TP53) should be performed; results of therapeutically actionable tests such as FLT3 should be available quickly so that targeted therapy can be started in time.
- Panel consensus; based on the phase 3 RATIFY trial
In patients with FLT3 mutation who are fit for intensive therapy, adding midostaurin to "7+3" induction (cytarabine + anthracycline) and consolidation is recommended.
- Panel consensus; based on the phase 3 VIALE-A and AGILE trials
In patients who are not candidates for intensive chemotherapy, venetoclax with a hypomethylating agent (azacitidine or decitabine) is the standard first-line treatment; in patients with IDH1 mutation, ivosidenib with azacitidine is another option.
- Panel consensus (not graded)
Monitoring of measurable residual disease (MRD) by molecular methods (qPCR) in patients with NPM1 mutation or CBF fusions, and by multiparameter flow cytometry in other patients, is part of response assessment and is used in decisions on allogeneic transplantation.
Study population
Adults with acute myeloid leukaemia (AML); covering diagnosis, genetic risk classification, response criteria, monitoring of measurable residual disease (MRD) and treatment.
Clinical significance and place in guidelines
The ELN 2022 genetic risk classification is the basis for decisions on allogeneic transplantation in first remission and for the design of new trials. The guideline incorporates approved targeted therapies (midostaurin, venetoclax with a hypomethylating agent, IDH inhibitors) into the treatment algorithm. Since its publication, newer drugs such as quizartinib (QuANTUM-First) and menin inhibitors (revumenib) have been approved and are not covered in this edition; in 2024 the ELN also proposed a separate risk classification for patients receiving less intensive therapy.
Limitations
The recommendations are based on expert consensus and have no formal grading of the level of evidence. This edition was published before the approval of quizartinib and menin inhibitors. The full text of the paper was not available for this summary; the recommendations were compiled from the ELN 2022 risk classification table (which has also been reproduced in open-access secondary sources) and its well-known treatment recommendations, and should be checked against the original text.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.