The parameters set to determine which patients can enroll in clinical trials testing new multiple myeloma treatments may disproportionately exclude patients from racial and ethnic minority groups, according to a new study published by Kanapuru et al in the journal Blood.
Background
Multiple myeloma is the second most common type of blood cancer in the United States—with about 34,500 new cases diagnosed in 2022. Black individuals may be twice as likely to be diagnosed with multiple myeloma compared with White individuals and have the highest rate of mortality from the disease, followed by American Indians and Alaska Natives. However, Black patients comprise less than 5% of those enrolled in clinical trials designed to test new multiple myeloma treatments with the goal of U.S. Food and Drug Administration (FDA) approval. The proportion of American Indians and Alaska Natives who are enrolled in these trials is even smaller. Previous studies have shown a history of minority underrepresentation in multiple myeloma clinical trials.
“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,” explained lead study author Bindu Kanapuru, MD, a medical officer in the Division of Hematology Products in the Office of Hematology and Oncology Products at the Center for Drug Evaluation and Research at the FDA. “We found that, compared with White patients … Black [patients] or [those] of other races—American Indians, Alaska Natives, Native Hawaiians, and other Pacific Islanders—were more likely to be deemed ineligible for trial enrollment,” she added.
All clinical trials set criteria that patients must satisfy to enroll. For example, patients may be required to have already been treated unsuccessfully with specific medications, have received a minimum number of prior treatments, have blood cell counts above or below a specified level, or not have comorbidities such as heart disease or a history of asthma.
“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,” Dr. Kanapuru noted.
Study Methods and Results
In the new study, the investigators analyzed the data of 9,325 patients who were evaluated for enrollment in 16 clinical trials of novel treatments for multiple myeloma from 2006 to 2019. Among the patients, 83% of them identified as White, 7% identified as Asian, 4% identified as Black, 4% were of unknown race, and 2% identified as other—which included American Indians, Alaska Natives, Native Hawaiians, and other Pacific Islanders. Additionally, 4% of the patients reported being of Hispanic ethnicity.
After conducting their research, the investigators discovered that 17% of the patients were deemed ineligible for trial enrollment. The ineligibility rate was highest among Black patients at 24%, followed by patients who identified as other races at 23%, compared with 17% among White patients. Patients of Asian heritage had the lowest rate of ineligibility at 11%.
The investigators revealed that Black patients were most often excluded as a result of their blood cell counts or because they had not previously received specific treatments or a minimum number of prior therapies. White patients were most often excluded because they did not meet specific disease-related criteria.
“Previous studies in patients with multiple myeloma have shown that ‘normal’ levels of neutrophils may be lower among Black patients than White [patients] and that Black patients have higher rates of anemia than White [patients],” Dr. Kanapuru stressed. “This suggests that trials should set criteria for blood counts that take racial and ethnic variations into account,” she emphasized.
These studies have also 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,” Dr. Kanapuru underscored.
Conclusions
The investigators noted that one of the findings from the new study included that a subset of Black patients were enrolled in multiple myeloma clinical trials despite not meeting some of the eligibility criteria such as low blood counts.
“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,” suggested Dr. Kanapuru. “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,” she advised.
In April 2022, the FDA published draft guidance on strategies that may increase the enrollment of underrepresented racial and ethnic groups in clinical trials. Nevertheless, because so few patients from racial and ethnic minorities were evaluated for trial enrollment, the investigators in the current trial were not able to 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. However, we hope that our study will raise awareness of this issue,” Dr. Kanapuru concluded.
Disclosure: For full disclosures of the study authors, visit ashpublications.org.
