Clinical trials of new cancer drugs may be inadvertently excluding individuals with the Duffy-null phenotype, which is more common in people of African or Middle Eastern descent. This phenotype results in lower levels of white blood cells called neutrophils in the blood, although these cells are often located in other body tissues. Current eligibility tests for clinical trials and dosing recommendations for cancer drugs are based on white blood cell levels and may not be appropriate for individuals with the Duffy-null phenotype.
Existing tests that measure neutrophil levels in the blood are used to determine whether patients can safely receive chemotherapy or other anti-cancer drugs. However, individuals with the Duffy-null phenotype may have lower levels of neutrophils in their blood but higher levels in other tissues. This can lead to the misinterpretation of neutrophil counts and exclusion of potentially eligible participants from clinical trials, as levels below a certain threshold may disqualify them from the trial.
The researchers analyzed major phase III trials for the five most prevalent cancers in the US and UK and found that a significant portion of these trials excluded patients with normal neutrophil counts for those with the Duffy-null phenotype. Furthermore, clinical trial protocols often require the modification of drug doses based on neutrophil levels, leading to lower or delayed doses for some individuals who could tolerate regular doses. Survival rates may be lower for patients receiving modified doses of cancer drugs.
Based on their findings, the researchers recommend that clinical trials of cancer drugs allow entry for patients with normal-for-them neutrophil counts, considering their Duffy-null phenotype. Individuals should be tested for this phenotype during screening, and if their counts are within the reference range for the Duffy-null group, they should be admitted to the trial. Similarly, dosing modifications should be based on the individual’s phenotype and neutrophil counts to ensure they receive appropriate treatment.
The study was funded by several organizations, including the National Institutes of Health and the Wellcome Trust. The researchers stress the importance of addressing inequities in cancer treatment and research, with a particular focus on hidden contributors such as neutrophil criteria for clinical trials and dose modifications. They call for action to amend these criteria to ensure that individuals with the Duffy-null phenotype are not disadvantaged in accessing potentially beneficial cancer therapies. Follow-up studies are needed to assess the safety and effectiveness of administering full doses to individuals with this phenotype and lower neutrophil counts.
