Although the 2022 European LeukemiaNet (ELN) genetic-risk stratification accurately reflects outcomes with respect to complete remission (CR) and relapse rates, disease-free survival (DFS), and overall survival (OS) in patients with de novo acute myeloid leukemia (AML), it is not an improvement over the 2017 ELN stratification, according to a study published in Leukemia.
Ann-Kathrin Eisfeld, MD, of The Ohio State University College of Medicine, and colleagues conducted an analysis of 1,637 adult patients diagnosed with de novo AML between 1986 and 2013. They analyzed the correlation between genetic-risk stratification and patient outcomes, compared performance of the 2017 and 2022 ELN stratification in age and ethnicity cohorts, and evaluated the prognostic potential of additions to the criteria used by the 2022 ELN genetic-risk stratification.
Researchers found a strong association between the 2022 ELN genetic-risk groups and outcomes. Specifically, the 2022 ELN stratification was found to reflect better outcomes of patients classified in the favorable risk group compared with those in the intermediate and adverse risk groups, and in the intermediate risk group compared with the adverse risk group with regard to CR (p<0.001) and relapse rates (p<0.001), DFS (five-year rates, p<0.001), and OS (five-year rates, p<0.001). However, researchers found little difference in the predictive ability of the 2022 and 2017 ELN genetic-risk stratifications regarding CR (area under the curve [AUC] p=0.44) and relapse rates (p=0.74), DFS (p=0.74), or OS (p=0.15).
With regard to age and ethnicity cohorts, researchers found there was little difference in outcomes between intermediate and adverse groups in older patients (60 years or older) except in CR rates. As such, data support the need to separate younger from older adults in future ELN recommendations for AML classification, they noted. Moreover, with the 2022 ELN guidelines, the DFS of African American patients who were younger than 60 was not statistically different between favorable and intermediate groups (p=0.42), nor was there a significant difference between intermediate and adverse groups in DFS (p=0.30, p=0.42) or OS (p=0.46, p=0.67) in African American or Hispanic patients.
“What people need to understand is that ELN guidelines are mainly reflective of patients younger than 60 years and of Central European ancestry,” Dr. Eisfeld said.
Finally, patients with myelodysplasia-related gene mutations, who were added to the 2022 ELN adverse-risk group, had similar CR rates (p=0.75) and DFS (p=0.10) as other patients in the adverse risk group but longer OS (p=0.005). Moreover, outcomes of patients in the favorable risk group were not adversely affected by the presence of myelodysplasia-related gene mutations, except in patient with NPM1-mutated/FLT3-ITD-negative disease and whose CR (p=0.02), DFS (p=0.03), and OS (p=0.005) were worse than those of patients without myelodysplasia-related mutations. This affected group had outcomes similar to those in the ELN 2022 intermediate risk group, underscoring that co-occurring myelodysplasia-related mutations affect favorable risk patient subsets differently.
Study findings indicate a need to modify risk assignment and to confirm results in larger patient cohorts. Additionally, “we need additional studies to validate some of the molecular changes [in ELN 2022 classification], and of course, always see the context of the patient,” Dr. Eisfeld said.
The study was limited in the size of some patient subgroups in the 2022 ELN stratification, as well as its inability to evaluate outcomes of patients with such newly added cytogenetic markers as t(8;16)/KAT6A::CREBBP, t(3;v)(q26.2;v)/MECOM(EVI1)-rearranged, or hyperdiploid complex karyotypes without structural abnormalities, which occurred in too few patients for meaningful analyses, calling for increased collaboration among large AML study groups.
Any conflicts of interest declared by the authors can be found in the original article.
Mrózek K, Kohlschmidt J, Blachly JS, et al. Outcome prediction by the 2022 European LeukemiaNet genetic-risk classification for adults with acute myeloid leukemia: an Alliance study [published online ahead of print, 2023 Feb 23]. Leukemia. doi: 10.1038/s41375-023-01846-8.