In a study of children with KMT2A-rearranged (KMT2A-r) acute myeloid leukemia (AML), the presence of flow cytometry-based measurable residual disease (flow-MRD) appeared to be a prognostic factor when detected at end of induction 2 (EOI2). Study findings were presented in the Journal of Clinical Oncology.
This retrospective study was conducted by the International Berlin-Frankfurt-Münster Study Group and included patients younger than 19 years old who had received a diagnosis of KMT2A-r AML between 2005 and 2016. Patients were stratified for analyses by risk status based on KMT2A fusion partners.
In this analysis, the research team had an aim of identifying the prognostic value of flow-MRD status when measured at EOI2. They additionally had a goal of assessing the benefit of allogeneic stem cell transplantation (allo-SCT) in first complete remission (CR1). Flow-MRD status was considered positive at a level of ≥0.1%. Clinical outcomes evaluated in this study included 5-year probabilities of event-free survival (EFS), cumulative incidence of relapse (CIR), and overall survival (OS).
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A total of 1130 patients were included in the study, with 728 (64.4%) being in the non-high-risk group and 402 (35.6%) being in the high-risk group. Median patient ages at diagnosis were 2.7 years in the non-high-risk group and 3.0 years in the high-risk group.
Overall, the 5-year EFS rate was 45.3%, the 5-year CIR rate was 44.0%, and the 5-year OS rate was 62.8%. Risk status was associated with EFS, CIR, and OS outcomes. The EFS rate for patients in the high-risk group was 30.3%, compared with 54.0% for the non–high-risk group (P <.0001). The CIR was 59.7% for the high-risk group, in comparison with 35.2% for the non-high-risk group (P <.0001). OS rates were 49.2% for high-risk patients and 70.5% for non-high-risk patients (P <.0001).
EOI2 flow-MRD negativity also appeared to be prognostic in this population. Patients showing flow-MRD negativity at EOI2 had an EFS of 47.6%, compared with 16.3% in patients showing flow-MRD positivity at EOI2 (P <.0001).
The OS rate was 66.0% with flow-MRD negativity, while it was 27.9% with flow-MRD positivity (P <.0001). The CIR values were 46.1% with flow-MRD negativity and 65.4% with flow-MRD positivity (P =.016). Multivariable analyses showed EOI2 flow-MRD positivity and high-risk status to each be factors independently associated with poorer EFS, CIR, and OS.
OS did not appear improved with allo-SCT in CR1 for the population overall (HR, 1.0; 95% CI, 0.7-1.3; P =.99) or within risk groups. However, in the high-risk patients of this study, allo-SCT in CR1 was associated with a significantly lower CIR (HR, 0.5; 95% CI, 0.4-0.8; P =.00096). For the non-high-risk patients, allo-SCT in CR1 did not significantly affect CIR (HR, 0.6; 95% CI, 0.4-1.0; P =.058).
“We conclude that EOI2 flow-MRD response and fusion partner-based risk group should be included as risk stratification factors in childhood KMT2A-r AML,” the study investigators wrote in their report. They also emphasized a need for novel approaches to treating high-risk patients.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.
Reference
van Weelderen RE, Klein K, Harrison CJ, et al. Measurable residual disease and fusion partner independently predict survival and relapse risk in childhood KMT2A-rearranged acute myeloid leukemia: a study by the International Berlin-Frankfurt-Münster Study Group. J Clin Oncol. Published online March 30, 2023. doi:10.1200/JCO.22.02120
