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. 2024 Oct 22;8(20):5297-5305.
doi: 10.1182/bloodadvances.2024013685.

Beat-AML 2024 ELN-refined risk stratification for older adults with newly diagnosed AML given lower-intensity therapy

Fieke W Hoff  1 , William G Blum  2 , Ying Huang  3 , Rina Li Welkie  3 , Ronan T Swords  4 , Elie Traer  4 , Eytan M Stein  5 , Tara L Lin  6 , Kellie J Archer  7 , Prapti A Patel  1 , Robert H Collins  1 , Maria R Baer  8 , Vu H Duong  8 , Martha L Arellano  2 , Wendy Stock  9 , Olatoyosi Odenike  9 , Robert L Redner  10 , Tibor Kovacsovics  11 , Michael W Deininger  12 , Joshua F Zeidner  13 , Rebecca L Olin  14 , Catherine C Smith  14 , James M Foran  15 , Gary J Schiller  16 , Emily K Curran  17 , Kristin L Koenig  3 , Nyla A Heerema  18 , Timothy Chen  3 , Molly Martycz  3 , Mona Stefanos  3 , Sonja G Marcus  19 , Leonard Rosenberg  19 , Brian J Druker  4 , Ross L Levine  5 , Amy Burd  19 , Ashley O Yocum  19 , Uma M Borate  3 , Alice S Mims  3 , John C Byrd  17 , Yazan F Madanat  1
Affiliations

Beat-AML 2024 ELN-refined risk stratification for older adults with newly diagnosed AML given lower-intensity therapy

Fieke W Hoff et al. Blood Adv. .

Abstract

Although the 2022 European LeukemiaNet (ELN) acute myeloid leukemia (AML) risk classification reliably predicts outcomes in younger patients treated with intensive chemotherapy, it is unclear whether it applies to adults ≥60 years treated with lower-intensity treatment (LIT). We aimed to test the prognostic impact of ELN risk in patients with newly diagnosed (ND) AML aged ≥60 years given LIT and to further refine risk stratification for these patients. A total of 595 patients were included: 11% had favorable-, 11% intermediate-, and 78% had adverse-risk AML. ELN risk was prognostic for overall survival (OS) (P < .001) but did not stratify favorable- from intermediate-risk (P = .71). Within adverse-risk AML, the impact of additional molecular abnormalities was further evaluated. Multivariable analysis was performed on a training set (n = 316) and identified IDH2 mutation as an independent favorable prognostic factor, and KRAS, MLL2, and TP53 mutations as unfavorable (P < .05). A "mutation score" was calculated for each combination of these mutations, assigning adverse-risk patients to 2 risk groups: -1 to 0 points ("Beat-AML intermediate") vs 1+ points ("Beat-AML adverse"). In the final refined risk classification, ELN favorable- and intermediate-risk were combined into a newly defined "Beat-AML favorable-risk" group, in addition to mutation scoring within the ELN adverse-risk group. This approach redefines risk for older patients with ND AML and proposes refined Beat-AML risk groups with improved discrimination for OS (2-year OS, 48% vs 33% vs 11%, respectively; P < .001), providing patients and providers additional information for treatment decision-making.

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Conflict of interest statement

Conflict-of-interest disclosure: W.G.B. has served on advisory boards of AbbVie and Syndax; and has received research funding from Immune-Onc Therapuetics, Meryx, and Nkarta. E.T. has participated in advisory boards and/or consulting for AbbVie, Astellas, Daiichi Sankyo, Servier, and Rigel; and has received research funding from Prelude Therapeutics, Schrodinger, Incyte, and AstraZeneca. E.M.S. has served on the advisory boards of Astellas Pharma, AbbVie, Genentech, Daiichi Sankyo, Novartis, Amgen, Seattle Genetics, Syros Pharmaceuticals, Syndax Pharmaceuticals, Agios Pharmaceuticals, and Celgene; and is an equity holder in Auron Therapeutics. T.L.L. has received research funding from BioPath Holdings, Astellas Pharma, Celyad Oncology, Aptevo Therapeutics, Cleave Biosciences, CicloMed, Jazz Pharmaceuticals, and Kura Oncology; and serves on the advisory board of Servier. P.A.P. has served on the advisory board of Agios Pharmaceuticals. M.R.B. has received institutional funding from AbbVie, Ascentage Pharma, Astellas, Gilead, Kura, and Takeda Pharmaceuticals. O.O. has served on the advisory boards of Servier, Rigel, AbbVie, Incyte; and the data safety monitoring board for Treadwell Therapeutics. T.K. has served on advisory boards of Astellas, Rigel, and Takeda; has received honoraria/consulting fees from Servier; and has received institutional research funds from AbbVie, Gilead, Novartis, and Syndax Pharmaceuticals. M.W.D. is a paid consultant for Novartis, Takeda Pharmaceuticals, Blueprint, Incyte, Dava Oncology, CTI BioPharma, Syneos, Cogent, Pfizer, and Dispersol. J.F.Z. has received honoraria from advisory boards from AbbVie, Bristol Myers Squibb (BMS), Daiichi Sankyo, Gilead, Immunogen, Servier, and Shattuck Labs; has received consulting fees from AbbVie, Foghorn, Novartis, Gilead, Sellas, Servier, and Sumitomo Dainippon Pharma; and has received research funding from AbbVie, Arog, Astex, Jazz, Gilead, Merck, Newave, Shattuck Labs, Stemline Therapeutics, Sumitomo Dainippon Pharma, and Takeda Pharmaceuticals. R.L.O. has received research funds from Cellectis; and consulted for Actinium, Astellas, AbbVie, Rigel, and Servier. C.C.S. has received research funds from AbbVie, BMS, Erasca, Revolution Medicines, and Zentalis Pharmaceuticals; and served on advisory boards for AbbVie, Genentech, and Astellas. G.J.S. has commercial interests in BMS, Amgen, and Johnson & Johnson; has received fees from AbbVie, Agios, Amgen, Astellas, BMS, Incyte, Janssen, Jazz, Karyopharm, Kite, Pharmacyclics, Sanofi/Genzyme, and Stemline Therapeutics; and has received research funds from AbbVie, Actinium, Actuate, Arog, Astellas, AltruBio, AVM Biotechnology, BMS/Celgene, Celator, Constellation, Daiichi Sankyo, Deciphera, Delta-Fly, Forma, Fujifilm, Gamida, Genentech-Roche, Glycomimetics, Geron, Incyte, Karyopharm, Kiadis, Kite/Gilead, Kura, Marker, Mateon, Onconova Therapeutics, Pfizer, Precog, REGiMMUNE, Samus, Sangamo Therapuetics, SELLAS, Stemline Therapeutics, Syros, Takeda Pharamceuticals, Tolero, Trovagene, Agios, Amgen, Jazz, Orca, ONO PHARMA -UK, and Novartis. M.S. has been a consultant for Eilean Therapeutics. B.J.D. has served on the scientific advisory boards for Adela Bio, Aileron Therapeutics (inactive), Therapy Architects/ALLCRON (inactive), Cepheid, Labcorp, Nemucore Medical Innovations, Novartis, and the RUNX1 Research Program; has served on the scientific advisory boards and holds stock in Aptose Biosciences, Blueprint Medicines, Enliven Therapeutics, Iterion Therapeutics, GRAIL, and Recludix Pharma; has served on boards of directors and holds stock in Amgen and Vincerx Pharma; has served on boards of directors for Burroughs Wellcome Fund and CureOne (inactive); has participated in the joint steering committee of Leukemia & Lymphoma Society’s Beat acute myeloid leukemia trial; has served on advisory committee for Multicancer Early Detection Consortium; is the founder of VB Therapeutics; has sponsored research agreements in AstraZeneca, DELiver Therapeutics, ImmunoForge, Terns, Enliven Therapeutics (inactive), and Recludix Pharma (inactive); has received clinical trial funding from Novartis and AstraZeneca; has received royalties from patent 6958335 (Novartis exclusive license) and Oregon Health & Science University and the Dana-Farber Cancer Institute (1 Merck exclusive license, 1 CytoImage, Inc exclusive license, 1 DELiver Therapeutics nonexclusive license, and 1 Sun Pharma Advanced Research Company nonexclusive license); and holds US Patents 4326534, 6958335, 7416873, 7592142, 10473667, 10664967, and 11049247. R.L.L. is on the supervisory board of Qiagen; is a scientific adviser to Imago, Mission Bio, and Syndax; receives equity support from Zentalis, Ajax, Bakx, Auron, Prelude, C4 Therapeutics, and IsoPlexis; receives research support from Ajax and AbbVie; has consulted for Incyte, Janssen, MorphoSys, and Novartis; and has received honoraria from AstraZeneca and Kura for invited lectures and from Gilead for grant reviews. U.M.B. has been a consultant for Genentech, Daiichi Sankyo, Takeda, Pfizer, AbbVie/Genentech, and Novartis. A.S.M. has served on the advisory boards of AbbVie/Genentech, Novartis, Ryvu Therapeutics, Rigel Therapeutics, Treadwell Therapeutics, and Foghorn Therapeutics. J.C.B. is a current equity holder in Vincerx Pharma Inc (a publicly traded company), Eilean Therapeutics, and Kurome Therapeutics; holds membership on the boards of directors or advisory committees of Vincerx, Newave, Eilean, Kartos, and Orange Grove Bio; and has been a consultant for and received honoraria from Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, and Syndax. Y.F.M. has received honoraria/consulting fees from BMS, Kura Oncology, Blueprint Medicines, Geron, OncLive, MD Education, VJHemOnc, and Medscape Live; has participated in advisory boards and received honoraria from Sierra Oncology, Stemline Therapeutics, Blueprint Medicines, MorphoSys, Taiho Oncology, Sobi, Rigel Pharmaceuticals, Geron, Cogent Biosciences, and Novartis; and has received travel reimbursement from Blueprint Medicines, MD Education, and MorphoSys. None of these relationships were related to this work. The remaining authors declare no competing financial interests.

The current affiliation for P.A.P. is Servier Pharmaceuticals, Boston, MA.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
ELN risk classification. (A) Proportion of patients (n = 595) with ELN favorable risk (blue), intermediate risk (yellow), and adverse risk (purple). The dashed fill shows the 2017 ELN classifications, and solid fill shows the 2022 ELN classification. (B) Alluvial plot comparing 2017 ELN (left) with 2022 ELN (right).
Figure 2.
Figure 2.
Distribution of the 10 gene mutations most significantly associated with 2022 ELN risk. Colors indicate the 2022 ELN risk groups: favorable risk (blue), intermediate risk (yellow), and adverse risk (purple).
Figure 3.
Figure 3.
Survival analysis by ELN risk. Survival analysis in patients with ND AML aged ≥60 years treated with LIT by (A) 2022 ELN and by (B) the Beat-AML 2024 ELN-refined risk.
See this image and copyright information in PMC

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