Summary
Socioeconomic status has been identified for the first time as a key contributor to disparities among children with acute myeloid leukemia (AML) who were enrolled in clinical trials. Children from poorer neighborhoods were 2.4 times more likely to die during treatment for AML than children from middle- and high-income neighborhoods in a study that analyzed nearly 1,500 clinical trial participants (Abstract 703).
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Original Article
Socioeconomic Disparities Affect Survival of Children in AML Clinical Trials
Oncology Times
By Mark L. Fuerst
Socioeconomic status has been identified for the first time as a key contributor to disparities among children with acute myeloid leukemia (AML) who were enrolled in clinical trials. Children from poorer neighborhoods were 2.4 times more likely to die during treatment for AML than children from middle- and high-income neighborhoods in a study that analyzed nearly 1,500 clinical trial participants (Abstract 703).
Previous research has pointed to racial disparities in cancer survival, but the new findings are especially alarming given that clinical trials are designed to provide consistent treatment across all participant groups. The fact that disparities were found despite the rigorous setting of clinical trials suggests that these disparities arise from factors outside of the specific chemotherapy used.
“Adult single center and registry studies have evaluated socioeconomic status as a predicator of survival in AML with conflicting results, showing from 15 percent to 33 percent increased risk of death among patients from the poorest neighborhoods. Lack of insurance and public insurance have also been associated with inferior survival,” said lead author Lena E. Winestone, MD, a pediatric hematologist and oncologist at the UCSF Benioff Children’s Hospital in San Francisco, at a press briefing at the 2019 ASH Annual Meeting.
“We expected there to be a difference, but the degree of difference is quite substantial. The more people are cognizant about the disparities that exist, the better positioned we will be to ameliorate them.”
Study Details
In the study, researchers at UCSF Benioff Children’s Hospital and the Children’s Hospital of Philadelphia examined data from children enrolled in the two most recent Children’s Oncology Group (COG) phase III clinical trials for AML, AAML1031 and AAML0531, and used U.S. Census data to determine the median income and educational attainment in patients’ neighborhoods. Of 2,387 patients enrolled in the two studies, 1,726 patients met inclusion criteria for the overall analysis. Due to missing covariate data, 1,467 patients were included in the final model.
The researchers found that neighborhood socioeconomic factors were significant predictors of survival, even after accounting for insurance type, race, and known biologic risk factors. Race/ethnicity differed significantly by area-based income, area-based education, and insurance type, with a higher proportion of black and Hispanic patients living in poverty, low income, and low education areas, and having Medicaid-only insurance. Lower area-based income was associated with lower overall survival (OS) (43% in poverty vs. 61% in low income vs. 68% in middle/high income) and event-free survival (EFS) (34% in poverty vs. 46% in low income vs. 54% in middle/high income).
A significantly higher proportion of Black and Hispanic patients lived in poverty, low income, and low education areas. Researchers found that the racial disparity persisted even after accounting for neighborhood socioeconomic factors, suggesting black patients face a significantly higher risk of death than white children living in areas of the same socioeconomic level.
Lower area-based educational attainment was also associated with lower OS, with 58 percent OS in Quartile 4 (lower education) versus 70 percent in Quartile 1 (higher education) and also lower EFS (44% in Quartile 4 vs. 54% in Quartile 1). Patients with Medicaid-only insurance had lower OS (59% vs. 66%), but similar EFS (48% vs. 50%). In a full multivariable model, the researchers found differences in survival by area-based educational attainment and insurance type resolved, suggesting that observed crude associations were explained by confounding by area-based income combined with established risk factors.
“Higher income children have 27 percent lower risk of dying. Disparities among black patients persist after accounting for socioeconomic status,” said Winestone. Similar differences by income were found in EFS.
There was no meaningful confounding of the income-survival association detected as evidenced by unchanged magnitudes of association following adjustment for area-based education, insurance, and established risk factors. Area-based low income was associated with both higher risk of early death and treatment-related mortality on therapy compared to area-based middle/high income.
The study did not determine the reasons behind the increased risk of death. One possibility is that toxic stress, which has been linked with lower socioeconomic status, may impact responses to chemotherapy or immune recovery following chemotherapy, said Winestone. The researchers plan to further examine when patients died and the cause of death in the hopes of gaining insights as to whether the risks are connected to treatment-related causes or to the cancer itself.
The researchers concluded: “Lower area-based income and education were associated with significantly inferior EFS and OS among patients with AML on the last two phase III COG trials. Moreover, zip code-based low socioeconomic status is an independent risk factor for mortality in pediatric AML. Additional studies to understand mechanisms of observed socioeconomic disparities in treatment outcomes will inform interventions that may mitigate these inequities.”
In addition to drawing attention to persistent racial and socioeconomic disparities in cancer outcomes, the results also highlight potential additional data to be collected as part of clinical trials. Rather than relying on neighborhood data as a proxy, Winestone said it would be helpful if future clinical trials collected individual data on participants’ socioeconomic status at the time of enrollment. “If we could gather that information, it would allow us to dig deeper into the question of how someone’s circumstances outside of the clinical aspects of their disease impact their health outcomes.”
In conclusion Winestone said, “This is the first national evaluation of socioeconomic status in pediatric AML. We found increased mortality among those from low income areas. Greater frequency of complications following chemotherapy accounts for some of the increased mortality.”
Mark L. Fuerst is a contributing writer.