In 2010 the European LeukemiaNet (ELN) organization convened a panel to address and develop guidelines for the diagnosis and management of acute myeloid leukemia (AML). The guidelines have since evolved, with the most recent updates being in 2017 and 2022 (ELN- 2022). The latest set of guidelines introduced changes to the stratification of risk methodology, including additional myelodysplasia-related mutations as adverse-risk markers, which has increased the number of patients who are classified as adverse-risk.
The Prognostic Significance of Guideline Changes
Since the ELN guidelines for AML have been applied to numerous practices in Europe and beyond, the study and validation of the 2022 changes were undertaken by Klaus H. Metzeler, MD, and colleagues. The research team conducted a study to determine the applicability and value of the guideline changes, the findings of which were published in Leukemia.
“While the proposed changes [in the ELN-2022 guidelines] individually are supported by published data, the effects of these modifications on overall risk stratification have not yet been validated in large and homogeneously treated cohorts,” Dr. Metzeler and colleagues wrote. They clarified the focus of their work by saying, “We set out to test the prognostic relevance of the ELN-2022 classification in intensively treated AML patients and to compare this revised risk stratification to the prior ELN-2017 system.”
Agreement Between Guidelines Was Observed in 85% of Patients
The study included 1,138 patients with a recent diagnosis of AML and a median age of 58 years (range, 18-86 years). A total of 1,118 patients were grouped based on their risk according to ELN-2022. About 32% (n=363) were categorized as having favorable risk, 27% (n=302) as having intermediate risk, and 41% (n=453) as having adverse risk. Similar to ELN-2017, older age was associated with increased risk in patients according to ELN-2022. Patients younger than 60 (n=600) were categorized as 39% favorable, 30% intermediate, and 31% as adverse-risk, whereas patients older than 60 (n=518) were categorized as 25%, 24%, and 52%, respectively (P<0.0001 for ELN favorable/intermediate vs adverse). Male sex (P=0.003) and secondary AML (P=0.0006) were also associated with increased risk.
Substantial agreement between the ELN-2017 and ELN- 2022 guidelines was observed in that 85% of patients remained in the same risk group under both guidelines. This was confirmed by Cohen’s kappa (unweighted kappa, 0.73; 95% CI, 0.77-0.80; weighted kappa, 0.84; 95% CI, 0.87-0.89).
Further Refinement of ELN-2022 Would Be Feasible by Using Existing Markers
The outcomes of patients reclassified from ELN- 2017 versus ELN-2022 shed light on the viability of the updated guidelines (Figure). Patients who were reclassified from the ELN-2017 favorable-risk category to the ELN-2022 intermediate-risk category (n=61) had a numerically higher 5-year overall survival (OS) rate compared with ELN-2022 intermediate- risk patients (48% vs 33%; P=0.307). Patients who were reclassified from the ELN-2017 adverse-risk category to the ELN-2022 intermediate- risk category (n=21) had a worse 5-year OS than other intermediate-risk patients (10% vs 33%; P=0.068); this reclassified group also had a significantly worse OS than patients reclassified from the ELN-2017 favorable-risk category to the ELN-2022 intermediate-risk category (P=0.016). Patients who were reclassified from ELN-2017 intermediate-risk category to the ELN-2022 adverse- risk category (n=68) achieved significantly improved 5-year OS than other adverse-risk patients (25% vs 12%; P=0.007).
“Our data suggest the [myelodysplasia-related] mutations newly classified as adverse-risk markers drive this change and should be more appropriately included in the intermediate-risk category,” Dr. Metzeler and colleagues wrote. “Further refinement of ELN-2022, especially to emphasize the unmet need of patients with a very poor prognosis, would be feasible by using markers already included in the classifier.”
