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Prognostic Impact of the AML60+ Score for Elderly Patients with Acute Myeloid Leukemia Treated with Hypomethylating Agents: A Retrospective Multicentric Analysis
by
, , ,
Verena Petermichl
1,†, 
Stefan Fuchs
2,†,
Matthias Weber
3,
Katrin Gobat
4,
Charlotte Micheloud
4,
Lukas Graf
5,
Yannick Gerth
5,
Jeroen S. Goede
6,
Thomas Lehmann
1,3,
Christoph Driessen
1,
Ulrich J. M. Mey
7,
Richard Cathomas
7,
Sergio Cogliatti
3 and
Tobias Silzle
1,7,* 1
Clinic for Medical Oncology and Hematology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
2
Department of Internal Medicine, Cantonal Hospital Graubünden, 7000 Chur, Switzerland
3
Institute of Pathology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
4
Swiss Cancer Institute, Statistics Unit, 3008 Bern, Switzerland
5
Center for Laboratory Medicine, St. Gallen, 9007 St. Gallen, Switzerland
6
Medical Oncology and Hematology, Cantonal Hospital Winterthur, 8400 Winterthur, Switzerland
7
Department of Medical Oncology and Hematology, Cantonal Hospital Graubünden, 7000 Chur, Switzerland
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2025, 17(16), 2658; https://doi.org/10.3390/cancers17162658
Submission received: 29 June 2025
/
Revised: 3 August 2025
/
Accepted: 11 August 2025
/
Published: 14 August 2025
(This article belongs to the Special Issue The New Challenge of Curing AML: Analysis of Mechanisms of Resistance of Target Drugs and Future Perspectives)
Simple Summary
The treatment of acute myeloid leukemia (AML) in elderly patients has changed significantly with the introduction of venetoclax in combination with hypomethylating agents (HMA). The AML60+ score was developed to identify elderly patients who would benefit from intensive chemotherapy and allogeneic stem cell transplantation. The aim of our retrospective and multicenter study was to determine whether the AML60+ is also helpful in assessing the prognosis of elderly AML patients receiving HMA-based therapy. Patients with lower risk according to AML60+ lived significantly longer than those within the higher risk categories. The C-index, as a comparative measure of prognostic significance, was higher for AML60+ than for the two indices used for comparison, the molecular Prognostic Scoring System and the European Leukemia Net 2022 classification. Given the small sample size, analyses of larger cohorts are needed to confirm our observation.
Abstract
Background: The AML60+ score has been proposed for risk stratification in intensively treated elderly patients with acute myeloid leukemia (AML) or high-risk myelodysplastic neoplasms (MDS). Its prognostic impact in patients treated with hypomethylating agents (HMA) is unknown. Methods: Patients ≥ 60 years of age diagnosed with AML or MDS/AML according to ICC2022 were eligible for this retrospective and multicenter chart review if they had received at least one cycle of HMA-based treatment. Results: A cohort of 142 patients was analyzed. During follow-up (median 8 months), 114 patients died. The molecular Prognostic Score (mPRS) was available for 121 patients, the European Leukemia Net (ELN) 2022 classification for 117 patients, and the AML60+ for 105 patients. According to AML60+, 33 patients (31.4%) were classified as very poor risk, 36 (34.3%) as poor risk, and 34 (32.4%) as intermediate risk. Two patients (1.9%) were classified as favorable. Median overall survival (OS) was 21.7 months (mo) for the combined intermediate/favorable group, 7 mo for the poor risk group and 3 mo for the very poor risk group (p < 0.0001). Cox regression analysis (reference category: very poor) showed a significantly lower risk of death for both intermediate/favorable risk patients (HR 0.17, 95% CI 0.10–0.31, p < 0.001) and poor risk patients (HR 0.47, 95% CI 0.28–0.78, p = 0.004). The concordance score was 0.67 for AML60+, 0.60 for mPRS, and 0.58 for ELN2022. Conclusions: The AML60+ may represent a useful prognostic tool for elderly AML patients treated with HMA-based therapies. In particular, it could help to identify a group with a relatively favorable prognosis that is not clearly identified by the ELN2022 or the mPRS risk classification. However, analyses of larger cohorts are necessary to confirm our findings.
Keywords:
acute myeloid leukemia; prognostication; hypomethylating agents; venetoclax; ELN2022; mPRS; AML60+
