High early death rates, treatment resistance, and short survival of Black adolescents and young adults with AML

Abstract

Survival of patients with acute myeloid leukemia (AML) is inversely associated with age, but the impact of race on outcomes of adolescent and young adult (AYA, 18-39-year-old) patients is unknown. We compared survival of 89 Non-Hispanic Black AYA AML patients with survival of 566 Non-Hispanic White patients treated on frontline Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology protocols. Samples of 327 patients (50 Black and 277 White) were analyzed via targeted sequencing. Integrated genomic profiling was performed on select longitudinal samples. Black patients had worse outcomes, especially those aged 18-29 years, who had a higher early death rate (16% vs 3%, P=.002), lower complete remission rate (66% vs 83%, P=.01), and decreased overall survival (OS; 5-year rates: 22% vs 51%, P<.001) compared with White patients. Survival disparities persisted across cytogenetic groups: 18-29-year-old Black patients with non-core-binding-factor(CBF)-AML had worse OS than White patients (5-year rates: 12% vs 44%, P<.001), including patients with cytogenetically normal AML (13% vs 50%, P=0.003). Genetic features differed, including lower frequencies of normal karyotypes and NPM1 and bi-allelic CEBPA mutations, and higher frequencies of CBF rearrangements and ASXL1, BCOR, and KRAS mutations in Black patients. Integrated genomic analysis identified both known and novel somatic variants, and relative clonal stability at relapse. Reduced response rates to induction chemotherapy and leukemic clone persistence suggest a need for different treatment intensities and/or modalities in Black AYA patients with AML. Higher early death rates suggest a delay in diagnosis and treatment, calling for systematic changes to patient care.

Outcome prediction by the 2022 European LeukemiaNet genetic-risk classification for adults with acute myeloid leukemia: an Alliance study

“…We found no significant differences in survival between 2022 ELN favorable and intermediate and between intermediate and groups in patients of African-American ancestry, and no significant difference in DFS between favorable and intermediate groups in Hispanic patients. Although these results may be in part related to the relatively low number of patients we were able to analyze, previously identified racial/ ethnic differences in the distribution of genetic alterations and outcomes [49][50][51][52][53] warrant application of 2022 ELN criteria to larger cohorts of African-American and Hispanic patients to confirm or refute our observations. Among major aims of our study was evaluation of the new markers used for 2022 ELN group assignment.…”

Disparities in acute myeloid leukemia treatments and outcomes

“…When analyzing gene mutation frequencies of known AML-associated molecular lesions, the high frequency of core-binding factor (CBF) rearrangements and specifically t (8;21) in Black patients has been repeatedly reported [20]. Interestingly, this increased frequency seems to be especially pronounced in adolescent and young adult (AYA, aged 18–39 years) AML patients, in whom CBF-AML accounts for 37% of Black AML patients, compared to 22% of White patients in the same age group: in young Black patients t(8;21) accounted for 59% of CBF-AMLs, compared to 46% in White patients [36 ▪ ]. This predominance of t(8;21) was also seen in pediatric Black AML patients, in whom t(8;21) was twice as frequent compared to non-Hispanic Whites [37].…”

MatchMiner open‐source platform matches patients with cancer to precision medicine trials

“…Dr Klein is the senior author of a recent study describing MatchMiner and various aspects of its use, including an assessment of its clinical impact based on the speed with which patients consent to participating in precision medicine trials when MatchMiner is used in comparison with when it is not. 1…”

“…"For example, you can match patients to trials based on a specific amino acid alteration (e.g., KRAS G12C) and cancer type (e.g., non-small cell lung cancer), and also exclude specific alterations and cancer types from matching," says Dr Klein, adding that there is no limit to the number of inclusions or exclusions for a given trial curation.Dr Klein is the senior author of a recent study describing MatchMiner and various aspects of its use, including an assessment of its clinical impact based on the speed with which patients consent to participating in precision medicine trials when MatchMiner is used in comparison with when it is not. 1…”