Narrow eligibility criteria may contribute to underrepresentation of racial and ethnic subgroups in cancer clinical trials of new medical treatments for multiple myeloma.
This conclusion is based on the result of a retrospective study of pooled analysis of multi-center, global clinical trials published in Blood, a peer-reviewed publication published by the American Society of Hematology (ASH).
The study results suggest that, for clinical trials of new treatments for multiple myeloma (a type of blood cancer), one reason for this underrepresentation may be that the parameters set to determine who can – and cannot – enroll in trials disproportionately exclude minority patients. [1]
“Our study suggests that, in multiple myeloma clinical trials, some eligibility criteria specified in trial protocols may be contributing to racial and ethnic disparities in enrollment,” said Bindu Kanapuru, MD, a medical officer with the U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research and first author of the study.
“We found that, compared with white patients, those who were Black or of other races (American Indians, Alaska Natives, Native Hawaiians, and other Pacific Islanders) were more likely to be deemed ineligible for trial enrollment.”
Selection criteria
“All clinical trials set criteria that patients must satisfy to enroll,” she said.
“For example, patients may be required to have already been treated unsuccessfully with specific medications, received a minimum number of prior treatments, have blood cell counts above or below a specified level, or not have other health conditions such as heart disease or a history of asthma,” Kanapuru said.
“To our knowledge, this is the first study to evaluate trial eligibility criteria as a potential barrier to the enrollment of patients from underrepresented racial and ethnic subgroups into clinical trials for multiple myeloma,” Kanapuru added.
Incidence
Multiple myeloma is the second most common type of blood cancer in the United States. According to the American Cancer Society about 35,730 new cases of multiple myeloma will be diagnosed (estimated at 19,860 in men and 15,870 in women) in 2023, while about 12,590 deaths are expected to occur (7,000 in men and 5,590 in women).
“In the United States, Black people are twice as likely as whites to be diagnosed with multiple myeloma and have the highest rates of death from the disease, followed by American Indians and Alaska Natives. Yet Black patients comprise less than 5% of those enrolled in clinical trials that are intended to lead to the approval of new treatments for multiple myeloma,” Kanapuru said, “While the proportion of American Indians and Alaska Natives who are enrolled is even smaller,” she added.
For this study, Kanapuru and her colleagues analyzed information submitted to the FDA for 9,325 patients who were evaluated for enrollment in 16 clinical trials of novel treatments for multiple myeloma that were performed between 2006 and 2019.
Twelve percent of the patients were evaluated in the United States and 88% in other countries. Eighty-three percent of the patients were white, 7% Asian, 4% Black, 4% of unknown race, and 2% of “other” races (which included American Indians, Alaska Natives, Native Hawaiians, and other Pacific Islanders). Four percent of patients reported being of Hispanic ethnicity.
Ineligibility rate
Overall, 17% of the evaluated patients were deemed ineligible for trial enrollment. The ineligibility rate was highest for Black patients (24%), followed by those of ‘other’ races (23%). Seventeen percent of white patients were deemed ineligible. Patients of Asian heritage had the lowest rate of ineligibility (11%).
The study results showed that Black patients were most likely to be considered ineligible because of their blood cell counts or because they had not previously received specific treatments or a minimum number of prior treatments. In contrast, white patients were most likely to be ineligible due to not meeting specific disease-related criteria.
“Previous studies in patients with multiple myeloma have shown that ‘normal’ levels of neutrophils (a type of white blood cell) may be lower among Black patients than whites and that Black patients have higher rates of anemia (a shortage of red blood cells) than whites,” Kanapuru explained.
“This suggests that trials should set criteria for blood counts that take racial and ethnic variations into account,” she added.
Other studies, Kanapuru said, have shown that Black patients with multiple myeloma are less likely to receive certain standard therapies.
“This can result in a cycle in which Black patients aren’t enrolled in trials because they haven’t previously received certain treatments, which in turn means there’s a lack of evidence to show whether or not those treatments are effective in Black patients,” Kanapuru added.
“One notable finding from the current study is that a subset of Black patients were enrolled in trials despite not meeting some of the eligibility criteria such as low blood counts,” said Kanapuru said
“This suggests that some physicians may already be factoring in racial and ethnic variations in things like blood counts when they evaluate patients for trial eligibility. While this is encouraging, the actions of individual physicians are unlikely to be enough to solve the problem of racial and ethnic disparities in trial enrollment,” Kanapuru observed.
Guidance for Industry
“The FDA has published guidance for industry on strategies for increasing the enrollment of underrepresented racial and ethnic groups in clinical trials,” Kanapuru noted. [3]
A limitation of the study findings, she said, is that because so few patients from racial and ethnic minorities were evaluated for trial enrollment, the researchers could not perform a rigorous statistical analysis to determine with greater precision why patients were deemed ineligible.
“The very small numbers of minority patients who were evaluated makes it impossible for us to draw definitive conclusions,” she said.
“However, we hope that our study will raise awareness of this issue,” she concluded
Reference
[1] Kanapuru B, Fernandes L, Baines AC, Ershler R, Bhatnagar V, Pulte E, Gwise T, Theoret MR, Pazdur R, Fashoyin-Aje LA, Gormley N. Eligibility criteria and Enrollment of a Diverse Racial and Ethnic population in Multiple Myeloma Clinical Trials. Blood. 2023 May 4:blood.2022018657. doi: 10.1182/blood.2022018657. Epub ahead of print. PMID: 37140031.
[2] Key Statistics About Multiple Myeloma. American Cancer Society (ACS). Online. Last accesses on May 4, 2023.
[3] Diversity Plans to Improve Enrollment of Participants From Underrepresented Racial and Ethnic Populations in Clinical Trials; Draft Guidance for Industry; Availability
Draft Guidance for Industry, U.S. Food and Drug Administration. April 2022. Online. Las assessed on May 4, 2023
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