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. 2023 Apr;37(4):788-798.
doi: 10.1038/s41375-023-01846-8. Epub 2023 Feb 23.

Outcome prediction by the 2022 European LeukemiaNet genetic-risk classification for adults with acute myeloid leukemia: an Alliance study

Krzysztof Mrózek #  1 , Jessica Kohlschmidt #  2   3 , James S Blachly  4   5 , Deedra Nicolet  2   3 , Andrew J Carroll  6 , Kellie J Archer  7 , Alice S Mims  4   5 , Karilyn T Larkin  2   4   5 , Shelley Orwick  4   5 , Christopher C Oakes  4   5 , Jonathan E Kolitz  8 , Bayard L Powell  9 , William G Blum  10 , Guido Marcucci  11 , Maria R Baer  12 , Geoffrey L Uy  13 , Wendy Stock  14 , John C Byrd  15 , Ann-Kathrin Eisfeld  16   17   18
Affiliations

Outcome prediction by the 2022 European LeukemiaNet genetic-risk classification for adults with acute myeloid leukemia: an Alliance study

Krzysztof Mrózek et al. Leukemia. 2023 Apr.

Abstract

Recently, the European LeukemiaNet (ELN) revised its genetic-risk classification of acute myeloid leukemia (AML). We categorized 1637 adults with AML treated with cytarabine/anthracycline regimens according to the 2022 and 2017 ELN classifications. Compared with the 2017 ELN classification, 2022 favorable group decreased from 40% to 35% and adverse group increased from 37% to 41% of patients. The 2022 genetic-risk groups seemed to accurately reflect treatment outcomes in all patients and patients aged <60 years, but in patients aged ≥60 years, relapse rates, disease-free (DFS) and overall (OS) survival were not significantly different between intermediate and adverse groups. In younger African-American patients, DFS and OS did not differ between intermediate-risk and adverse-risk patients nor did DFS between favorable and intermediate groups. In Hispanic patients, DFS and OS did not differ between favorable and intermediate groups. Outcome prediction abilities of 2022 and 2017 ELN classifications were similar. Among favorable-risk patients, myelodysplasia-related mutations did not affect patients with CEBPAbZIP mutations or core-binding factor AML, but changed risk assignment of NPM1-mutated/FLT3-ITD-negative patients to intermediate. NPM1-mutated patients with adverse-risk cytogenetic abnormalities were closer prognostically to the intermediate than adverse group. Our analyses both confirm and challenge prognostic significance of some of the newly added markers.

Trial registration: ClinicalTrials.gov NCT00048958 NCT00899223 NCT00900224.

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Conflict of interest statement

JSB is a consultant for and reported honoraria from KITE, INNATE, AstraZeneca and AbbVie. ASM received research funding from Leukemia and Lymphoma Society’s Beat AML clinical study, Aptevo, Daiichi Sankyo, Glycomemetics, Kartos Pharmaceuticals, Xencor and Genentech; and is a consultant for Aptevo, Abbvie, BMS, Glycomemetics, Jazz Pharmaceuticals, Kura Oncology, and Syndax Pharmaceuticals. BLP is a consultant for Cornerstone Pharmaceuticals and reported research funding from Ambit Biosciences, Cornerstone, Genentech, Hoffman LaRoche, Jazz Pharmaceuticals, Novartis and Pfizer. WGB reported honoraria from Abbvie, Syndax, and AmerisourceBergen and research funding from Celyad Oncology, Nkarta, Xencor, Forma Therapeutics and Leukemia and Lymphoma Society. GLU is a consultant for AbbVie, Agios, Jazz, GlaxoSmithKline, Genentech, and Novartis; reported honoraria from Astellas and research funding from Macrogenics. JCB consults for Astellas, AstraZeneca, Novartis, Pharmacyclics, Syndax and Trillium; receives honoraria from Astellas, AstraZeneca, Novartis, Pharmacyclics, Syndax and Trillium; he is a Chairman of the Scientific Advisory Board of Vincerx Pharmaceuticals and a member of advisory committee of Newave; and is a current equity holder of Vincerx Pharmaceuticals. A-KE is the spouse of Christopher J. Walker who is currently employed by Karyopharm Therapeutics. The remaining authors declare no competing financial interests.

Figures

Fig. 1
Fig. 1. Distribution of the genetic-risk groups and outcome of all patients with de novo acute myeloid leukemia categorized into the three genetic-risk groups according to the 2022 European LeukemiaNet (ELN) recommendations.
a Bar charts depicting the distribution of the genetic-risk groups in all patients categorized according to the 2022 ELN classification and of those grouped according to the 2017 ELN guidelines. b Disease-free survival and c overall survival of all patients classified according to the 2022 ELN guidelines.
Fig. 2
Fig. 2. Distribution of the genetic-risk groups and outcome of younger adults under the age of 60 years with de novo acute myeloid leukemia categorized into the three genetic-risk groups according to the 2022 European LeukemiaNet (ELN) recommendations.
a Bar charts depicting the distribution of the genetic-risk groups in younger patients categorized according to the 2022 ELN classification and of those grouped according to the 2017 ELN guidelines. b Disease-free survival and c overall survival of younger patients classified according to the 2022 ELN guidelines.
Fig. 3
Fig. 3. Distribution of the genetic-risk groups and outcome of older patients aged 60 years or older with de novo acute myeloid leukemia categorized into the three genetic-risk groups according to the 2022 European LeukemiaNet (ELN) recommendations.
a Bar charts depicting the distribution of the genetic-risk groups in older patients categorized according to the 2022 ELN classification and of those grouped according to the 2017 ELN guidelines. b Disease-free survival and c overall survival of older patients classified according to the 2022 ELN guidelines.
Fig. 4
Fig. 4. Outcomes of patients with de novo acute myeloid leukemia categorized according to the presence or absence of myelodysplasia-related mutations.
a Disease-free survival and b overall survival of patients with myelodysplasia-related mutations with and those without favorable-risk AML subtypes, and of patients in the 2022 ELN adverse group who do not harbor myelodysplasia-related mutations. c Disease-free survival and d overall survival of patients in the 2022 ELN favorable group with myelodysplasia-related mutations and favorable-risk AML subtypes, and of patients in the 2022 ELN favorable group who do not have myelodysplasia-related mutations. e Disease-free survival and f overall survival of patients in the 2022 ELN favorable group with NPM1 mutations, no FLT3-ITD and myelodysplasia-related mutations, and of patients in the 2022 ELN favorable group with NPM1 mutations without FLT3-ITD or myelodysplasia-related mutations.
Fig. 5
Fig. 5. Outcomes of patients with de novo acute myeloid leukemia categorized according to the criteria newly introduced by the 2022 European LeukemiaNet recommendations.
a Disease-free survival and b overall survival of patients with NPM1 mutations and no FLT3-ITD categorized according to the presence or absence of adverse-risk cytogenetic features. Outcomes of patients classified in the 2022 ELN favorable and adverse (excluding NPM1-mutated patients with adverse-risk cytogenetic features) groups are shown for comparison. c Disease-free survival and d overall survival of intermediate-risk patients who harbor FLT3-ITD, compared with other patients included in the intermediate group and of patients in the adverse group.
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