High Early Death Rates, Treatment Resistance and Short Survival of Black Adolescent and Young Adults (AYAs) with Acute Myeloid Leukemia (AML) (Alliance)

Background: AML is a highly aggressive hematologic malignancy. Patient (pt) outcomes are affected by disease-related factors including cytogenetic findings and gene mutations, as well as pt-related factors, such as age and race. Younger pts have superior survival: ~50% of pts diagnosed as AYAs (18-39 years) may be cured of their disease. However, the impact of race on the outcome and associated disease profiles in this pt population are unknown. Methods: We compared survival and molecular profiles of 655 Non-Hispanic Black and Non-Hispanic White (hereafter referred to as Black, n=89 and White, n=566) AYA AML pts treated on frontline Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology protocols based on standard intensity cytarabine/anthracycline induction therapy between 1986 and 2016. Three hundred ten pts were analyzed molecularly via targeted sequencing of 81 genes. Additionally, we performed integrated genomic profiling (whole-exome sequencing and transcriptome sequencing) and measured residual disease (MRD) in serial samples of 4 Black pts who relapsed with their disease. Results: A comparison of clinical characteristics of AYA AML pts by race revealed almost identical age and sex distribution, and we found no significant differences between clinical features at diagnosis. With regard to genetic profiles, 42% of White pts were cytogenetically normal, whereas only 18% of Black pts had cytogenetically normal AML (CN-AML; p