Clinical trials for cancer drugs often exclude individuals with the Duffy-null phenotype, a common genetic trait among people of African and Middle Eastern descent, according to a study published in JAMA Network Open. This exclusion is due to the fact that individuals with the Duffy-null phenotype tend to have lower neutrophil counts, which are misinterpreted as a sign of increased risk of infection during cancer treatment. This practice leads to health inequity in cancer treatment and research.
The Duffy-Null Phenotype and Neutrophil Levels
The Duffy-null phenotype results in naturally lower levels of neutrophils in the blood. Neutrophils are white blood cells crucial for fighting infections, and their levels are closely monitored during cancer treatment, especially with chemotherapy, which can further reduce these counts. Clinical trials often set a minimum neutrophil count threshold for participation to ensure patient safety. However, these thresholds are typically based on studies of European descent populations, where the Duffy-null phenotype is rare.
"People with the Duffy-null phenotype are equally able to fight off infections compared to others," said Andrew Hantel of Dana-Farber Cancer Institute. "The concern is that they've been excluded from clinical trials because the neutrophil blood levels that are normal for them can fall below the cut-off points for trial participation. In this study, we explored the extent to which this occurs."
Exclusion Rates in Clinical Trials
The study examined 289 Phase III clinical trials for the five most prevalent cancers in the U.S. and the U.K.: prostate, breast, colorectal, lung cancer, and melanoma. The researchers found that 76.5% of these trials excluded patients whose neutrophil counts were within the normal range for individuals with the Duffy-null phenotype. Colorectal cancer trials had the highest exclusion rate at 86.4%.
Impact on Treatment Regimens
The researchers also reviewed 71 clinical trials that led to National Comprehensive Cancer Network (NCCN) recommended treatment regimens. They discovered that over half of these trials required reducing the drug dose, delaying administration, or stopping treatment if a participant's neutrophil count fell below a level considered normal for people with the Duffy-null phenotype. This can lead to less effective treatment for these patients.
"The effect of these recommendations is to inappropriately reduce the intensity of treatment for patients who would likely tolerate regular doses," Hantel explained.
Recommendations for Change
The study authors recommend that clinical trials of cancer drugs should allow entry to patients with neutrophil counts that are normal for individuals with the Duffy-null phenotype. They suggest that everyone being screened for trial entry should be tested for the Duffy-null phenotype, and if they are Duffy-null and their counts are within the reference range for that group, they should be admitted.
Stephen Hibbs of Queen Mary University of London emphasized the need to re-examine how neutrophil count misinterpretation affects patient care, stating, "Neutrophil criteria for clinical trials and dose modifications are a hidden contributor to inequity that can be rectified. Now, action to amend these criteria is needed to ensure Duffy-null patients are not disadvantaged."
