Clinical Context

In the United States in 2021, hematologic malignancies accounted for ~ 10% of all cancer incidence and deaths. Healthcare disparities in blood cancers are an ongoing problem.

Race, ethnicity, and age are linked to survival differences, partly because of health care-related barriers experienced by racial minorities and older adults. Unequal distribution of trial sites warrants examination of their geographic accessibility.

Study Synopsis and Perspective

Black and minority groups are significantly underrepresented in major drug trials for leukemias and multiple myeloma (MM) compared with the proportions of these groups in the broader patient population, a new study concludes.

“Our analysis shows that, over the past 10 years, participation in pivotal clinical trials investigating therapies for leukemias and MM is unrepresentative of the US population,” said the authors, led by Jorge E. Cortes, MD, of the Georgia Cancer Center at Augusta University, Augusta, Georgia.

“Trials should represent the population with the disease,” they commented.

The study was published online August 9 in the Journal of Clinical Oncology.^[1]

“This study confirms that the US cancer population for select hematologic malignancies was inadequately racially and ethnically represented in studies leading to drug approval,” commented the authors of an accompanying editorial.^[2]

“The results from this study should lead to questions about the generalizability of drug safety and efficacy in populations we serve as medical hematologists and oncologists,” said Mikkael A. Sekeres, MD, along with Namrata S. Chandhok, MD, both of the division of hematology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida.

They posed the question, for instance, that as physicians practicing in South Florida, where most of their patients are Hispanic, “can we apply the results of these pivotal studies -- and drug labels -- to them, without any sense of whether they metabolize the drug the same way as those included in the study or have the same biologic targets?”

For their study, Cortes and colleagues analyzed 61 pivotal trials for leukemia and MM leading to approval of the drugs from the FDA between 2011 and 2021.

They found that only two-thirds (67.2%) of these trials reported data pertaining to race, whereas about half (48.8%) reported on ethnicity.

The trials that did report data on race involved a total of 13,731 patients. The vast majority (81.6%) were White, and Black patients represented only 3.8%. Asian/Pacific Islanders made up 9.1%, and American Indians or Alaskan Natives made up just 0.12% of participants, with 1.5% categorized as other.

Among the trials reporting on ethnicity, 4.7% of patients were Hispanic, with 11.5% being Hispanic in acute lymphoblastic leukemia (ALL) trials and 7.6% Hispanic in chronic myeloid leukemia (CML) trials.

Slightly more than half (54.8%) of all trial participants were male, and patients’ average ages ranged from 41.7 to 70.1 years across all malignancies.

Of the minority groups, Asian/Pacific Islanders and Blacks had the highest representation in trials involving CML, at 12.7% and 5.3%, respectively.

Their lowest representation was in chronic lymphocytic leukemia (CLL), at 3% and 1.1%, respectively.

Among the trials reporting ethnicity, Hispanics were the highest representation, with percentages ranging from 2.9% of MM trials to 11.5% in ALL trials.

Next, the researchers compared the proportions of race/ethnic groups that were found among the participants of these pivotal trials with the proportions that would be expected in patient populations for each of these blood cancers (according to the US Surveillance, Epidemiology, and End Results [SEER] database).

For example, Whites made up 80.3% of participants in clinical trials of MM, whereas they represent 68.7% of patients with MM, a difference that was statistically significant (P < .0001).

The finding was similar for CLL, with Whites accounting for 90.5% of participants in clinical trials vs 82.5% of the patient population (P < .0001).

For AML, the difference was smaller, with respective percentages of 79.6 vs 77.3% (P = .0389).

For Blacks, Asian/Pacific Islanders and Hispanics, across all 5 cancer types that were analyzed, the proportion of participants in clinical trials was significantly lower than the proportion in the patient population.

The analysis also showed that female persons were overrepresented in clinical trials for 2 blood cancers. For MM, trial participation was 44.7%, whereas disease incidence was 41.7% (P < .0001), and for CML, the proportions were 44.7% vs 39.5% (P = .0009); however, female persons were underrepresented in a third blood cancer: In AML, the proportions were 44.7% vs 60.5% (P < .0001).

The study also highlighted an obstacle to minorities participating in clinical trials: geography.

For AML, they found mortality rates were high across the whole of the United States, but centers conducting AML clinical trials were primarily in the Northeast, with no centers in the Midwest.

Key regions with high rates of AML mortality, low access to trials, and high minority representation were notably clustered in areas including east of the Carolinas, south Georgia, Alabama, and Mississippi, the authors noted.

“In many instances, trials were absent in areas with high mortality,” they reported. “This makes access to clinical trials difficult, if not impossible, to patients who do not have the financial means for travel.”

Racial and ethnic disparities in clinical trials have been widely reported in numerous previous studies, the authors noted.

For oncology, the American Society of Clinical Oncology (ASCO^®) has also taken steps with the release of the new Equity, Diversity, and Inclusion Action Plan in 2021 to improve representation of minorities in research.

Cortes and colleagues suggested another step that is needed is standardized reporting of demographics of clinical trial participants.

“More importantly, efforts to increase representation of minorities and disadvantaged populations in clinical trials should be prioritized,” they said.

Cortes reports a consulting role and receiving research funding from many pharmaceutical companies. No other coauthors have financial disclosures. Chandhok reports honoraria from Clinical Care Options and Healio and a consulting role with SERVIER. Sekeres reports a consulting role with Celgene Corporation; Kurome Therapeutics; Millennium Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Pfizer, Inc.; and Syros Pharmaceuticals and institutional research funding from Actuate Therapeutics, Inc. (Inst); Bio-Path Holdings, Inc. (Inst); Bristol-Myers Squibb Company; Pfizer, Inc.; SELLAS Life Sciences Group (Inst), and Takeda Pharmaceuticals North America, Inc.

Clinical Implications

• There are significant demographic and geographic underrepresentation and imbalances in pivotal clinical trials leading to drug approvals for blood cancers compared with affected populations.
• These disparities must be addressed to ensure applicability of results to all relevant populations.
• Implications for the Healthcare Team: Drug safety and efficacy data may not be generalizable to minority populations; therefore healthcare team members must be aware of current disparities with clinical trials in hematologic malignancies to prevent disparities in future population outcomes.

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