New Risk Stratification Model Provides Prognostic Data on Survival Post-AlloHCT for Older Patients With AML and High-Risk MDS

According to research published in the Journal of Clinical Oncology, a novel risk model, the AML60+ classification, provided prognostic information for intensively treated patients aged 60+ years with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (HR-MDS), while identifying patients who would benefit from intensive chemotherapy and allogeneic hematopoietic cell transplantation (alloHCT).

“Overall, the outcome of patients older than 60 years with AML remains poor compared with younger patients, despite treatment advances, with decreased morphological complete remission (CR) rates, shorter duration of CR, and poorer overall survival (OS),” stated lead study author Jurjen Versluis, MD, PhD, Erasmus University Medical Center Cancer Institute, Rotterdam, the Netherlands, and colleagues, explaining “Despite…the older age preponderance of patients with AML, prognostic models have been based on younger patients leading to uncertainty as to which older patients are optimally treated with intensive chemotherapy, with or without alloHCT.”

To attempt to address this issue, the new AML60+ risk stratification system identified 4 groups in patients aged 60+ with AML and HR-MDS and provides information on outcomes after intensive induction chemotherapy. Investigators examined 1,910 intensively treated patients aged 60+ years with AML and HR-MDS from 2 cohorts (NCRI-AML18 and HOVON-SAKK). Using a random survival forest as a predictive algorithm, clinical, molecular, and cytogenetic variables were evaluated in an AML development cohort (n = 1,204) for association with OS. Additionally, relative weights of selected variables determined the prognostic model, which was validated in the AML (n = 491) and HR-MDS cohorts (n = 215).

Study results demonstrated 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%). Additionally, 9 variables were used to construct the 4 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).

Study authors demonstrated a significant OS benefit of allo-HCT in the patients with AML assigned to the AML60+ intermediate- and very poor-risk group and an indication for better OS in the AML60+ poor-risk group. Although the OS benefit of allo-HCT in these older patients appeared to be relatively modest, the cumulative incidence of relapse was reduced by allo-HCT in all risk groups, which the study authors took to point to a strong graft-versus-leukemia effect.

On the other hand, since this benefit was counterbalanced by increased [non-relapse mortality] NRM in all risk groups, the investigators noted that this emphasizes the importance of patient-specific evaluation of NRM and deployment of existing, and new, strategies to reduce its risk.

Overall, “AML60+ provides a novel prognostic score that is easy to apply to current routine clinical practice and crucially provides information on survival post-alloHCT. By using AML60+, clinicians will better be able to assess the relative benefit from alloHCT and balance that against the potential NRM assessed by specific risk scores,” concluded Dr Versluis and colleagues.

“Similar to all prognostic classifications, AML60+ will have to be refined as optimal treatment evolves,” they added.

Source:

Versluis J, Metzner M, Wang A, et al. Risk stratification in older intensively treated patients with AML. Published online September 4, 2024. doi: 10.1200/JCO.23.02631