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Risk stratification in older intensively treated patients with AML
Versluis, J. Metzner, M. Wang, A. Gradowska, P. Thomas, A. Jakobsen, N. A. Kennedy, A. Moore, R. Boertjes, E. Vonk, C. M.
Versluis, J.
Metzner, M.
Wang, A.
Gradowska, P.
Thomas, A.
Jakobsen, N. A.
Kennedy, A.
Moore, R.
Boertjes, E.
Vonk, C. M.
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Abstract
PURPOSE: AML is a genetically heterogeneous disease, particularly in older patients. In patients older than 60 years, survival rates are variable after the most important curative approach, intensive chemotherapy followed by allogeneic hematopoietic cell transplantation (allo-HCT). Thus, there is an urgent need in clinical practice for a prognostic model to identify older patients with AML who benefit from curative treatment. METHODS: We studied 1,910 intensively treated patients older than 60 years with AML and high-risk myelodysplastic syndrome (HR-MDS) from two cohorts (NCRI-AML18 and HOVON-SAKK). The median patient age was 67 years. Using a random survival forest, clinical, molecular, and cytogenetic variables were evaluated in an AML development cohort (n = 1,204) for association with overall survival (OS). Relative weights of selected variables determined the prognostic model, which was validated in AML (n = 491) and HR-MDS cohorts (n = 215). RESULTS: The complete cohort had a high frequency of poor-risk features, including 2022 European LeukemiaNet adverse-risk (57.3%), mutated TP53 (14.4%), and myelodysplasia-related genetic features (65.1%). Nine variables were used to construct four groups with highly distinct 4-year OS in the (1) AML development, (2) AML validation, and (3) HR-MDS test cohorts ([1] favorable: 54% ± 4%, intermediate: 38% ± 2%, poor: 21% ± 2%, very poor: 4% ± 1%; [2] 54% ± 9%, 43% ± 4%, 27% ± 4%, 4% ± 3%; and [3] 54% ± 10%, 33% ± 6%, 14% ± 5%, 0% ± 3%, respectively). This new AML60+ classification improves current prognostic classifications. Importantly, patients within the AML60+ intermediate- and very poor-risk group significantly benefited from allo-HCT, whereas the poor-risk patients showed an indication, albeit nonsignificant, for improved outcome after allo-HCT. CONCLUSION: The new AML60+ classification provides prognostic information for intensively treated patients 60 years and older with AML and HR-MDS and identifies patients who benefit from intensive chemotherapy and allo-HCT.
Authors
Versluis, J.
Metzner, M.
Wang, A.
Gradowska, P.
Thomas, A.
Jakobsen, N. A.
Kennedy, A.
Moore, R.
Boertjes, E.
Vonk, C. M.
Kavelaars, F. G.
Rijken, M.
Gilkes, A.
Schwab, C.
Beverloo, H. B.
Manz, M.
Visser, O.
Van Elssen, C.
de Weerdt, O.
Tick, L. W.
Biemond, B. J.
Vekemans, M. C.
Freeman, S. D.
Harrison, C. J.
Cook, J. A.
Dennis, Mike
Knapper, S.
Thomas, I.
Craddock, C.
Ossenkoppele, G. J.
Löwenberg, B.
Russell, N.
Valk, P. J. M.
Vyas, P.
Metzner, M.
Wang, A.
Gradowska, P.
Thomas, A.
Jakobsen, N. A.
Kennedy, A.
Moore, R.
Boertjes, E.
Vonk, C. M.
Kavelaars, F. G.
Rijken, M.
Gilkes, A.
Schwab, C.
Beverloo, H. B.
Manz, M.
Visser, O.
Van Elssen, C.
de Weerdt, O.
Tick, L. W.
Biemond, B. J.
Vekemans, M. C.
Freeman, S. D.
Harrison, C. J.
Cook, J. A.
Dennis, Mike
Knapper, S.
Thomas, I.
Craddock, C.
Ossenkoppele, G. J.
Löwenberg, B.
Russell, N.
Valk, P. J. M.
Vyas, P.
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Date
2024
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Article
Citation
Versluis J, Metzner M, Wang A, Gradowska P, Thomas A, Jakobsen NA, et al. Risk Stratification in Older Intensively Treated Patients With AML. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2024 Dec;42(34):4084-94. PubMed PMID: 39231389. Pubmed Central PMCID: PMC11608593 manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Paresh Vyas Leadership: Auron Therapeutics Stock and Other Ownership Interests: Auron Therapeutics, Yellowstone Biosciences Honoraria: Celgene, Pfizer, Jazz Pharmaceuticals, AbbVie, Daiichi Sankyo, Astellas Pharma Research Funding: Celgene Patents, Royalties, Other Intellectual Property: Patent for flow cytometric detection of leukemic stem cells No other potential conflicts of interest were reported. Epub 2024/09/04. eng.