Baseline laboratory values for AML clinical trials are setting unnecessary restrictions for kidney function that excludes African American patients with AML when this comorbidity does not impact overall survival.
African American patients with Acute Myeloid Leukemia (AML) were more likely to have evidence of abnormal kidney functioning than white patients, which excluded them unnecessarily from clinical trials in AML, according to research presented at the 2019 American Society of Hematology (ASH) Annual Meeting.
African American patients with cancer are underrepresented in clinical trials for cancer, in part due to restrictive eligibility criteria that do not take into account minority patient populations tending to have higher rates of comorbidities. This does not accurately reflect the real-world population that will receive the drug for treatment, said researchers from the Cleveland Clinic in a press briefing at ASH.
“It’s important that we understand how drugs work in different patient populations in clinical trials, especially those that reflect the patients we will eventually treat with the drug,” said lead study author Abby Statler, PhD, from the Cleveland Clinic Cancer Center. “Designers of clinical trials can use data from studies like ours to inform future eligibility criteria in order to test drugs in more diverse populations.”
Researchers investigated 1,040 adult patients with AML who received chemotherapy at the Cleveland Clinic from 2003 to 2019. In that group, 90.3% identified as white and only 9.7% identified as African American. According to the liver function laboratory values assigned for clinical trials in the treatment of patients with AML, a greater proportion of the African American patients presented with renal dysfunction compared to white patients, based on the measures of abnormal creatinine and creatinine clearance. Meaning, these were signs that the kidneys were not clearing waste products from the bloodstream as well as they normally should. However, these signs were most likely benign, because previous research has shown African Americans typically have higher levels of creatinine than whites.
Researchers also concluded that minimal abnormal creatinine levels did not impact overall survival (OS), as patients with minimal abnormal creatine levels had similar OS rates to patients with normal creatinine levels. The outcomes from this research suggest that the laboratory value may falsely underestimate this population’s kidney function and that it is safe for the design of the study to include African Americans with abnormal creatinine levels to AML clinical trials.
The OS for the entire cohort was 14.75 months and the median OS did not significantly differ by race. No comorbidities, except liver functions, impacted OS for the entire cohort. Treatment approaches and rates of responsiveness to treatment were also examined by researchers and showed no significant differences between African Americans and whites, which suggests the treatment worked just as well in both patient groups.
63% of the African American patients in this cohort ultimately presented with a renal function abnormality that would have likely excluded them from a clinical trial, explained Statler in a presentation of the findings from this study at ASH. “Our outcomes suggest that renal function is not associated with clinical outcomes,” she said. “Therefore, these data allow us to provide recommendations regarding how future clinical trials may design future eligibility criteria [in AML]. We specifically recommend liberalizing renal function eligibility criteria as this might promote the recruitment of more African Americans to clinical AML trials.”
Statler believes liberalizing renal function eligibility in clinical trials could be a major step towards accruing a more diverse population for AML clinical trials, which could lead to a reduction in recruitment racial disparities overall. Opening up novel therapy clinical trials to a broader patient group could ensure that more patients with AML have access to the potential benefits of novel therapies, as well as ensuring the trial results have a greater impact in a real-world setting.