Risk stratification in older intensively treated patients with AML

Versluis, Jurjen, Metzner, Marlen, Wang, Ariel, Gradowska, Patrycja, Thomas, Abin ORCID: https://orcid.org/0000-0002-8283-6762, Jakobsen, Niels Asger, Kennedy, Alison, Moore, Rachel, Boertjes, Emma, Vonk, Christian M., Kavelaars, Francois G., Rijken, Melissa, Gilkes, Amanda, Schwab, Claire, Beverloo, H. Berna, Manz, Markus, Visser, Otto, Van Elssen, Catharina H.M.J., de Weerdt, Okke, Tick, Lidwine W., Biemond, Bart J., Vekemans, Marie-Christiane, Freeman, Sylvie D., Harrison, Christine J., Cook, Jonathan A., Dennis, Mike, Knapper, Steven ORCID: https://orcid.org/0000-0002-6405-4441, Thomas, Ian, Craddock, Charles, Ossenkoppele, Gert J., Löwenberg, Bob, Russell, Nigel, Valk, Peter J.M. and Vyas, Paresh 2024. Risk stratification in older intensively treated patients with AML. Journal of Clinical Oncology 10.1200/JCO.23.02631

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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.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Medicine Centre for Trials Research (CNTRR)
Publisher:	American Society of Clinical Oncology
ISSN:	0732-183X
Date of First Compliant Deposit:	13 September 2024
Date of Acceptance:	9 July 2024
Last Modified:	16 Sep 2024 11:45
URI:	https://orca.cardiff.ac.uk/id/eprint/172099

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