Research led by the Dana-Farber Cancer Institute shows people with African or Middle Eastern ancestry may miss out on being included in cancer trials because of their Duffy blood group status.
The Duffy blood group refers to antigens found on the surface of red blood cells. Most people of European ancestry have Duffy antigens, but amongst people of African of Middle Eastern ancestry as many as two-thirds do not have these antigens on their red blood cells and are Duffy-null.
People who are Duffy-null often have low levels of neutrophils, a type of white blood cell, when their blood is tested. However, this is not damaging for them as they tend to have more of these cells in other tissues.
Having a low neutrophil count can exclude possible participants from cancer trials though, as this is added into most trials as a safety measure to ensure patients can be safely treated with chemotherapy and other anti-cancer drugs that may increase infection risk. If a person’s level is below a certain threshold value they are likely to be excluded from a clinical trial.
“People with the Duffy-null phenotype are equally able to fight off infections compared to others,” said lead author Andrew Hantel, a physician at the Dana-Farber Cancer Institute in Boston, in a press statement.
“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.”
In this study, published in JAMA Network Open, Hantel and colleagues assessed 289 Phase III clinical trials in adults for the five most common cancers in the U.S., namely, prostate, breast, melanoma, colorectal and lung cancer. They evaluated whether the trials automatically excluded people with neutrophil levels in the range normal for those with the Duffy null phenotype or whether anticancer therapy dose modifications are made for these individuals.
The results showed that 76.5% of the trials included in the study automatically excluded people with Duffy null blood neutrophil levels from participating. The highest exclusion rates were in colorectal cancer trials at 86.4% and the lowest in prostate cancer trials at 47.8%.
“The treatment guidelines set by the National Comprehensive Cancer Network, or NCCN, are based on the clinical trials in which those drugs were tested,” Hantel explained. “If a trial stipulates that the dosage should be lowered or delayed if a patient’s blood neutrophil count is below a certain level, doctors often use those modifications once the drug is approved as standard therapy. We know that in many cases, survival rates are lower for patients who receive lowered or delayed doses.”
The authors conclude that these practices “structurally discriminate against patients of African and Middle Eastern ancestry.” They concede that while finding the appropriate systemic anticancer therapy dose for people with the Duffy null phenotype requires more investigation, the exclusion criteria that stops these individuals from accessing cancer clinical trials should be changed.
