Risk Stratification in Older Intensively Treated Patients With AML-Reference-Cited by-同舟云学术

Risk Stratification in Older Intensively Treated Patients With AML

Published:2024-09-04 Issue: Volume: Page:
ISSN:0732-183X
Container-title:Journal of Clinical Oncology
language:en
Short-container-title:JCO

Author:

Versluis Jurjen¹^ORCID,Metzner Marlen²^ORCID,Wang Ariel³^ORCID,Gradowska Patrycja¹⁴,Thomas Abin⁵^ORCID,Jakobsen Niels Asger²^ORCID,Kennedy Alison²^ORCID,Moore Rachel²,Boertjes Emma¹^ORCID,Vonk Christian M.¹^ORCID,Kavelaars Francois G.¹,Rijken Melissa¹,Gilkes Amanda⁶^ORCID,Schwab Claire⁷,Beverloo H. Berna⁸^ORCID,Manz Markus⁹^ORCID,Visser Otto¹⁰,Van Elssen Catharina H.M.J.¹¹^ORCID,de Weerdt Okke¹²,Tick Lidwine W.¹³^ORCID,Biemond Bart J.¹⁴,Vekemans Marie-Christiane¹⁵,Freeman Sylvie D.¹⁶^ORCID,Harrison Christine J.⁷,Cook Jonathan A.¹⁷^ORCID,Dennis Mike¹⁸,Knapper Steven⁶^ORCID,Thomas Ian⁵,Craddock Charles¹⁹^ORCID,Ossenkoppele Gert J.²⁰,Löwenberg Bob¹^ORCID,Russell Nigel²¹^ORCID,Valk Peter J.M.¹^ORCID,Vyas Paresh²²²^ORCID

Affiliation:

1. Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, the Netherlands

2. MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom

3. Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom

4. HOVON Foundation, Rotterdam, the Netherlands

5. Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University, Cardiff, United Kingdom

6. School of Medicine, Cardiff University, Cardiff, United Kingdom

7. Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom

8. Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands

9. Department of Hematology, University Hospital Zurich, Zurich, Switzerland

10. Department of Hematology, Isala Hospital, Zwolle, the Netherlands

11. Maastricht University Medical Center, Maastricht, the Netherlands

12. Antonius Hospital, Nieuwegein, the Netherlands

13. Maxima Medical Center, Eindhoven, the Netherlands

14. Amsterdam UMC, Location AMC, Cancer Center Amsterdam, Amsterdam, the Netherlands

15. Cliniques Universitaires Saint-Luc, Brussels, Belgium

16. Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom

17. Oxford Clinical Trials Research Unit, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom

18. The Christie NHS Foundation Trust, Manchester, United Kingdom

19. Warwick Clinical Trials Unit, University of Warwick, Warwick, United Kingdom

20. Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, the Netherlands

21. Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom

22. Department of Haematology, Oxford University Hospitals NHS Trust and Oxford Biomedical Centre, Oxford, United Kingdom

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.

Publisher

American Society of Clinical Oncology (ASCO)

Link

https://ascopubs.org/doi/pdfdirect/10.1200/JCO.23.02631

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