ASH Study Examines Racial Disparities in AML Clinical Trials

Abby Statler, PhD

Closing the racial gap for patients in acute myeloid leukemia (AML) clinical trials could lead to better medications to treat the debilitating disease.

During the American Society of Hematology (ASH) 2019 annual meeting in Orlando, a team of investigators, led by Abby Statler, PhD, MPH, Cancer Biostatistics, the Cleveland Clinic, explored the validity of potential bias within acute myeloid leukemia (AML) and characterized the comorbidity profile, while comparing outcomes between African Americans and white patients with AML.

Minority patients are often underrepresented in clinical trial. For example, the amount of minority patients in cancer studies has decreased recently, especially among African Americans.

However, 1 reason to increase minority patients in clinical trials is that the minority patient populations generally have higher rates of comorbidities and restrictive eligibility criteria could possibly contribute to systematic exclusion from studies.

The study included 1040 adults with AML who receive chemotherapy at Cleveland Clinic from 2003-2019. Of the patients included in the study, 939 (90.3%) were white and 101 (9.7%) were African American.

The investigators analyzed age, sex, self-reported race, insurance, etiology of AML, comorbidities, hepatic/renal functioning tests, left ventricular ejection fraction (LVEF), and corrected QT interval (QTc).

AML risk was categorized according to the 2017 European LeukemiaNet (ELN) risk stratification and organ dysfunction was defined as ≥ grade 1 per the Common Terminology for Adverse Events.

The team also used multivariable logistic and Cox regression analyses to identify prognostic factors for response status per International Working Group criteria and overall survival.

Age, AML etiology, and AML risk were balanced between the 2 groups. Insurance coverage was different, with African Americans were more likely to have Medicaid (11.9% vs 5.1%), and less likely to have private insurance (16.8% vs 34.6%), (P <.001).

A total of 868 (83.5%) of the patients were treated with intensive, cytarabine-based treatment, while 172 (16.5%) of patients were treated with non-intensive regimens—low-dose cytarabine or hypomethylating agents.

The 2 groups were equally likely to receive intensive therapy (P = .68).

African American patients presented similar frequencies of both overall and specific comorbidities. Liver function laboratory values (AST/ALT/bilirubin) and cardiac test results (QTc/LVEF) at baseline were also similar, but a greater proportion of African American patients presented renal dysfunction when compared to white patients as measured by creatinine (48.5% vs. 36.5%, P = .01) or creatinine clearance by Cockcroft-Gault (CrCl; 55.4% vs. 47.3%, P = .01).

The median follow-up 12.73 months and the median overall survival for the cohort was 14.75 months and did not differ by race.

“Overall, the complete response (CR) rate was 44.2%, which also did not differ by race: (AA vs whites: 37.6% vs 44.9%, P = .19),” the author wrote. “When adjusting for other known predictors, in a multivariable analysis, there was no difference in OS between AAs and whites (HR, 1.20; P = .16); additionally, there was no association between comorbidities/organ dysfunction and OS, with the exception of liver comorbidities (HR, 2.03; P = .002) and bilirubin (>1.5 x ULN vs. normal: HR, 1.69; P = .01).”

With exception of liver comorbidities (OR, .17; P = .01), the analysis failed to identify significant evidence of association between response and comorbidities and organ dysfunction.

African Americans were also less likely to achieve a clinical response (AA vs. whites: OR, .56, P =.05), there was no association between response and creatinine/CrCl abnormalities, regardless of severity.

Overall, the investigators found some reasons why there is a discrepancy between the races for clinical trial enrollment.

“Within this cohort, renal function eligibility criteria may be an important barrier to enrollment, specifically within the AA population,” the authors wrote. “Since there is no association between clinically insignificant renal laboratory values and OS or response, the liberalization of such criterion may be justified.”

The investigators suggest that future trials should broaden the renal function eligibility criterion to potentially accrue more diverse patient populations, which could reduce recruitment racial disparities and improve the generalizability of the trials’ results.