Why are African Americans Underrepresented in Myeloma Clinical Trials?

HealthTree for Multiple Myeloma has been one of the leading patient-centric organizations advocating for increased participation of African Americans in myeloma clinical trials.

A recent paper published in the Journal Blood, authored by a group of researchers from the US Food and Drug Administration (FDA), helps us to understand some of the reasons for such underrepresentation.

This team pooled information from sixteen global clinical trials (9,325 patients), including information on race, reasons for screen failures, and trial ineligibility. The National Cancer Institute (NCI) reports that the incidence rate of myeloma in the United States is twice as high for African Americans as it is for whites, yet this study reports that across these sixteen clinical trials, whites comprised 84% of patients screened for trial participation and deemed eligible to participate in these trials. This compares to 4% of Black patients screened and considered eligible for trial participation. 

The authors presented several conclusions and suggestions:

“Comparing the reasons for trial ineligibility for Blacks versus the White subgroup, a higher percentage of Blacks failed to meet treatment related (17%) and hematology lab related (19%) eligibility criteria compared to Whites (12%, 10%).” 

The authors noted, "Blacks were more likely to be ineligible for a trial due to failure to meet hematology lab criteria and protocol specified treatment related criteria. The higher ineligibility rates due to hematologic lab criteria and failure to meet treatment-related criteria for Blacks are not surprising. Evidence from the literature suggests that racial differences exist in levels of neutrophil counts (benign neutropenia) and the threshold for normal neutrophil counts may be lower in Blacks compared to whites. Rates of anemia have also been reported to be higher in African American [multiple myeloma] patients compared to whites.”

“Prior studies in patient populations with myeloma have identified differences in access and receipt of therapies by race and ethnicity.” For example, “In a study that evaluated 639 patients with newly diagnosed myeloma from the Multiple Myeloma Research Foundation (MMRF) CoMMpass registry, African Americans were less likely to receive standard triplet therapies—alkylator, proteasome, or immunomodulatory based— and first-line autologous stem cell transplant compared to whites.”

“Stringent eligibility criteria requirements for normal or adequate organ function (e.g., renal, hepatic, cardiac) and minimal comorbidities have previously been reported as a potential barrier to enrollment of racial and ethnic minority groups in cancer clinical trials.” This issue is not new. The National Cancer Institute has also reported, “In the Community Cancer Center Program, a higher proportion of Non-Hispanic Blacks evaluated for breast, colorectal and genitourinary trials did not meet eligibility criteria for enrollment due to co-morbidities compared to the other racial groups.”

The authors make several recommendations to ensure that ethnic disparities for enrollment into multiple myeloma clinical trials are reduced/eliminated:

• “Clinical trial eligibility criteria should likely consider potential variations of laboratory values that occur due to race or ethnicity and consider broadening eligibility criteria for hematologic function.” The same goes for co-morbidities that may preclude trial participation.
• “Clinical trials...designed to support regulatory approval of an indication in a particular patient population often include eligibility criteria requiring a minimum number of prior lines of therapy or receipt of specific therapies. As Black patients may not have received the specified treatments for enrollment, thus, a delay in receipt or lack of receipt of standard-of-care therapy... can result in ineligibility and increase racial disparities in clinical trial enrollment. This...reduces the evidence to offer newer therapies to the racial and ethnic minority groups, propagating a cycle.”
• The authors advocate that cancer trials should be designed to “include patients with organ dysfunction and prior or concurrent malignancies, and including this information in the labeling can facilitate the safe and effective use of these products across a broader patient population likely to use the drug in clinical practice.”

The important topic of ensuring diversity in clinical trial participation has been addressed by the United States FDA in two recent publications. A viewpoint paper outlines “… a framework for increasing diversity in clinical trials … and potentially serves to facilitate future enrollment strategies for underrepresented racial and ethnic subgroups.”

In addition, the FDA has also issued draft guidance to the industry recommending that companies “… prospectively define a plan that includes but not limited to enrollment goals for underrepresented racial and ethnic study population and study design features that will allow for an assessment of safety and effectiveness during the entire clinical development of the product.”

For more thoughts on clinical trial participation and what might make patients hesitant to join (or unable to qualify), read here: 

• Understanding Patient Perspectives Toward Participation in Multiple Myeloma Clinical Trials
• Debunking Clinical Trial Myths with Dr. Craig Cole