Evolution of Survival Disparities Among Adolescents and Young Adults with AML in the US

Title: Evolution of Survival Disparities among Adolescents and Young Adults with AML in the US

Introduction: Prior work has shown survival disparities across social determinants of health amongst adolescents and young adults (AYAs) with acute myeloid leukemia (AML), particularly affecting minoritized groups. However, less is known about how these disparities have changed over time particularly in the rarer entity of AML amongst AYAs and in the context of significant advances over the past several decades. Therefore, we used the US national cancer database to examine changes in survival disparities over time amongst AYA patients with AML.

Methods: The National Cancer Database records approximately 70% of cancer diagnoses in the US. We used the AML database from 2004-2021 to evaluate racial and sex disparities in survival amongst patients aged 15-39 and across two eras (2004-2013 and 2014-2021). Multivariable Cox survival models defined hazard ratios according to sex and race (White, Black, Native American, South Asian, Southeast Asian, East Asian, Hawaiian/Pacific Islander). Interaction term analysis evaluated whether the degree of disparities has changed over time. Multivariable models were adjusted for relevant clinical and patient-level factors. Level of significance for p-interaction value is set to <0.1. All analyses were conducted using STATA 17.

Results: There were 17,710 AYA patients (51.2% female) with AML (Median age 30, interquartile range is 25-35). Out of all AYA patients with known race/ethnicity, 80.4% were White, 14.4% were Black, 1.55% were East Asian, 1.28% were South Asian, 1.17% were Southeast Asian, 0.66% were Native American, and 0.46% were Hawaiian/Pacific Islander. In a sample of 13,886 AYA patients with complete survival data, Black patients had worse survival compared to White patients (HR 1.21 95% CI 1.1-1.30). All other races demonstrate no significant difference in survival outcomes compared to White patients. Females had improved survival compared to males (HR 0.86 95% CI 0.82-0.91). Noninsurance and greater comorbidity were also independently associated with worse survival.

In the first treatment era (2004-2013), survival was better for females vs. males (female 5yr OS 57.1%, 95%CI 0.56-0.59, vs male 5yr OS 54.4%, 95%CI 0.53-0.56; HR 0.89, 95%CI 0.83-0.95, p=0.001). In the second era (2014-2021), survival was better for females than for males (female 5yr OS 68.9%, 95%CI 0.67-0.70, vs male 5yr OS 64.1%, 95% CI 0.62-0.66; HR 0.80, 95%CI 0.73-0.88). The degree of difference in survival by sex was greater in 2014-2021 than in 2004-2013 (p-interaction 0.082).

In contrast, 5yr OS for Black populations in the first era was 48.2% (95% CI 0.45-0.51) compared to White 57.1% (95% CI 0.56 – 0.58) with HR of 1.17 (95% CI 1.07-1.29, p=0.001). In the second era, 5yr OS for Black patients was 59.3% (95% CI 0.56-0.62) vs White 67.4 % (95% CI 0.66 – 0.69) with HR of 1.25 (95% CI 1.12-1.41). The degree of difference in survival by sex showed no change over time (p-interaction 0.234).

Discussion: Our study found significant changes in the difference in outcomes by sex. Although outcomes have improved for both sexes, the degree of improvement has been greater for AYA females versus males. In contrast, we found no significant change in disparities amongst race in AYAs with AML over decades with Black populations continuing to show poorer outcomes compared to White populations. Benefit related to advances in care over time may not have been equitably distributed amongst races, evidenced by the persistence in racial disparities in survival outcomes.

Conclusion: Our study of the evolution of disparities among AYAs with AML in the past two decades has shown no significant improvement and the persistence of worse outcomes of Black populations vs. White populations. However, we have seen a significant improvement in the outcomes of female vs. male AYAs. We encourage further studies to elucidate factors leading to improvements in outcomes for females AYAs with AML in order to better understand and explore how these advances can be equitably accessed among other groups.