Survival Outcomes in Young ALL Vary by Race/Ethnicity

While survival outcomes for children and young adults with acute lymphocytic leukemia (ALL) have improved significantly over the last several decades, substantial differences in outcomes by race and ethnicity continue to persist, a secondary analysis of eight Children’s Oncology Group (COG) trials showed.

Among over 21,000 eligible children, adolescents, and young adults who participated in COG trials from 2004 through 2019, the 5-year event-free survival (EFS) rate was 87.4% among white patients compared with 82.8% among Hispanic patients (HR 1.37, 95% CI 1.26-1.49, P<0.0001) and 81.8% among Black patients (HR 1.45, 95% CI 1.28-1.65, P<0.0001), reported Sumit Gupta, PhD, of the Hospital for Sick Children in Toronto, and colleagues.

In addition, 5-year overall survival (OS) rates were superior among Asian patients (93.6%) and white patients (93.3%) compared with Hispanic patients (89.9%), Black patients (89.7%), and non-Hispanic “other” patients (88.9%; P<0.0001 for all), they noted in Lancet Haematology.

In an audio conversation accompanying the study, Gupta explained that past studies have hypothesized that these disparities are linked to imbalances in disease prognosticators, socioeconomic status, or both.

Multivariable models of EFS and OS that included different combinations of race/ethnicity, insurance status, and disease prognosticators showed different patterns of risk attenuation depending on the group.

For example, the increased risk of an event among Hispanic patients was partly attenuated by adjusting for disease prognosticators (adjusted HR 1.17, 95% CI 1.06-1.29, P=0.0001) or insurance status (aHR 1.30, 95% CI 1.19-1.42, P<0.0001), and largely attenuated by both (aHR 1.11, 95% CI 1.00-1.22, P=0.045).

“So those two concepts of disease prognosticators and insurance status did account for some of that risk, but not all of it,” Gupta said.

However, the increased risk for Black patients was only minimally attenuated by adjusting for insurance status and disease prognosticators, decreasing to a HR of 1.32 (95% CI 1.14-1.52, P<0.0001), “suggesting that especially in children of Black race, there is something else going on in addition to those factors,” he added.

Of note, survival disparities were limited to patients with B-cell ALL, with no differences in EFS or OS observed among patients with T-cell ALL — “a novel finding that suggests that mechanisms related to the care received during the maintenance phase of therapy are notable in explaining outcome disparities given the larger role of maintenance in B-cell acute lymphoblastic leukemia,” Gupta and team wrote.

Furthermore, the wider disparities observed for OS compared with EFS “suggest disparities might be greater in the setting of relapsed disease versus newly diagnosed disease, hence access to or quality of treatments for relapsed disease are important,” they noted.

“Future research elucidating the mechanisms underlying these disparities should include studies of access to and quality of care, particularly during maintenance therapy and among relapsed patients,” they concluded.

In a commentary accompanying the study, Nada Hamad, MBBS, of St. Vincent’s Hospital in Sydney, Australia, noted that nearly two-thirds of the patients in the COG trials were white and that the other racial and ethnic groups were much smaller and therefore less likely to accurately represent real-world settings.

“If the goal is to cure acute lymphocytic leukemia in all children, it is necessary to design research questions that specifically redress unanswered questions for children of all ethnicities represented in our communities,” she wrote.

She suggested that clinical trials should not only prioritize the enrollment of diverse populations, but that “data on social determinants of health, ethnicity, gender, and other intersectional characteristics should be collected uniformly, organ function variables that are inclusive of ethnic variances should be used, and pharmacogenomics studying efficacy and toxicity have to become the new normal.”

This analysis included 21,152 patients up to age 30 with available race and ethnicity data (56% male) from eight completed COG trials. White patients comprised the largest racial/ethnic group (65.6%), followed by Hispanic patients (20.6%), Black patients (7.2%), Asian patients (5.1%), and non-Hispanic “other” patients (1.6%).

Insurance status varied by race and ethnicity, with approximately half of Hispanic and Black patients insured by Medicaid versus 18.6% of white patients.

In discussing study limitations, Gupta and team noted that “barriers to either clinical trial enrollment or to the accurate reporting of demographic factors that vary by race and ethnicity hinder understanding of the full spectrum of disease and outcomes across the population.”