Photo Credit: Nemes Laszlo

A new classification model called AML60+ improved risk stratification for older adults with acute myeloid leukemia, which can improve clinical decision making.

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A new risk stratification system aims to improve decision making on which older patients with acute myeloid leukemia (AML) will benefit most from intensive treatment, according to findings published in the Journal of Clinical Oncology.

“As there are age-dependent differences in the frequencies of genetic changes in AML and in toxicity profiles to intensive therapy, there is a need for prognostic risk classification for older, intensively treated patients with AML,” wrote Jurjen Versluis, MD, PhD, and colleagues. “Recently, a risk model for older patients with AML was developed, but this did not address which patients would optimally benefit from allogeneic hematopoietic cell transplantation (allo-HCT).”

Selecting Patients With AML

The study authors gathered clinical and genetic data from the NCRI-AML18 trial and four HOVON-SAKK trials. The overall cohort included 1,910 intensively treated patients aged 60 years and older who had newly diagnosed AML and high-risk myelodysplastic syndrome (HR-MDS).

The average age was 67 (range, 60-84), and most patients with AML were considered adverse risk according to the European Leukemia Network (ELN) 2022 classification. Patients had International Prognostic Scoring System (IPSS) scores of 1.5 or more, revised IPSS greater than 4.5, or excess blasts of 10% or more.

The researchers used machine learning to develop the new classification model in a subset of patients recruited between 2007 and 2016, deemed the AML development cohort (n=1,204; 63.0%). Then, the authors evaluated the model in a subgroup that received subsequent treatment between 2017 and 2018, referred to as the AML validation cohort (n=491; 25.7%), as well as an HR-MDS cohort (n=215; 11.2%).

AML60+ Classification & Prognostic Factors

Significant variables included:

• TP53 mutations (HR, 2.42)
• Monosomal karyotype (HR, 2.06)
• Age older than 65 years (HR, 1.50)
• White blood cell count greater than 20x10e9/L
• Male sex
• FLT3 internal tandem duplication
• DNMT3A, ASXL1, and RUNX1 mutations

The researchers used these variables to assign risk scores based on HRs, where TP53 mutations and monosomal karyotype were worth three points, age greater than 65 years two points, and the remaining variables one point each. The study authors grouped patients into four risk categories based on their total scores: favorable (0-1 points), intermediate (2-3 points), poor (4-6 points), and very poor (7-10 points).

The favorable-risk group had a significantly higher complete remission rate (90.3%) than the very poor-risk group (57.3%). Transplant rates followed a similar trend, with 45% of patients in the favorable group undergoing allo-HCT compared with 33.2% in the intermediate group, 24.5% in the poor group, and 29.4% in the very poor group.

In all cohorts, OS at 4 years progressively decreased across the risk groups. In the AML development cohort, OS rates were 54%, 38%, 21%, and 4%, in the favorable, intermediate, poor, and very poor groups, respectively. The researchers noted similar trends in the AML validation (52%, 43%, 27%, and 4%) and HR-MDS test cohorts (54%, 33%, 14%, and 0%). These patterns persisted even when censored for allo-HCT.

The AML60+ classification also showed that allo-HCT significantly improved OS in the intermediate-risk (51% vs 39%, P=0.01) and very poor-risk (12% vs 2%, P=0.03) subgroups compared with patients who did not receive allo-HCT. However, there was no significant OS difference in the favorable-risk (62% vs 53%, P=0.24) and poor-risk (35% vs 22%, P=0.07) groups.

Comparing Prognostic Models

The AML60+ revealed significant heterogeneity within each ELN 2022 risk group. Per the findings, 37% of patients considered adverse risk by ELN 2022 were reclassified to favorable or intermediate risk with the AML60+. In addition, 75% of patients with ELN 2022 favorable risk fell into intermediate or higher-risk categories under the new model.

The AML60+ model also improved OS stratification across all ELN 2022 risk groups. In the ELN 2022 favorable-risk group, where the 4-year OS was 53%, AML60+ further divided patients into subgroups with OS rates ranging from 66% (favorable) to 43% (poor). AML60+ also refined prognoses in the ELN 2022 intermediate- and adverse-risk groups. Of note, AML60+ identified a subgroup within the ELN2022 adverse-risk group that had markedly better outcomes (48% 4-year OS), as well as a very poor-risk subgroup with only a 3% 4-year OS.

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