Real-world generalizability of clinical trial cytomolecular risk in pediatric acute myeloid leukemia: a report from the REAL-AML cohort.

Cytomolecular features critical for risk-stratified treatment determination in pediatric acute myeloid leukemia (AML) were expanded in Children's Oncology Group (COG) Phase III trial AAML1831 based on previous trials. It remains unknown whether the cytomolecular risk profiles are generalizable to the real-world. We addressed this knowledge gap using a nationally representative real-world cohort of 913 pediatric AML patients. Distributions of cytomolecular risk profiles and individual markers were comparable for trial-enrolled and non-enrolled patients, as well as across social drivers of trial enrollment (race/ethnicity, language, insurance, acuity). Compared to patients with only favorable cytomolecular markers (4-year overall survival [OS] = 89.48%; 95% CI = 84.46% to 92.95%), patients with both favorable and unfavorable (hazards ratio [HR] = 2.49, 95% CI = 1.18 to 5.23), neutral (HR = 4.33, 95% CI = 2.75 to 6.82), and only unfavorable (HR = 5.80, 95% CI = 3.70 to 9.11) markers all had increased hazards of death. Cytomolecular risk informed by trial data appears to be generalizable to the real-world setting in pediatric AML.