Pivotal Multiple Myeloma, Leukemia Trials May Not Represent the Populations They Serve


Investigators identified underrepresentation and imbalances in demographic and geographic representation in clinical trials leading to FDA approvals.

Mycal Casey, DO, MPH

Mycal Casey, DO, MPH

Compared with the real-world populations most affected by leukemias and multiple myelomas, participants enrolled in clinical trials informing FDA approvals between 2011 and 2021 underrepresent key demographic and geographic populations, according to an analysis published in the Journal of Clinical Oncology.1

According to the analysis, 67.2% of trials which informed FDA approvals reported race (n = 41) and 48.8% (n = 20) reported ethnicity. In total the sample included 13,731 patients, of whom 11,209 (81.6%) were White and 524 patients were Black (3.8%). The percentage of Asian-Pacific Islander, American Indian/Alaskan Native, or other, were 9.1% (n = 1243), 0.12% (n = 16), and 1.5% (n = 199), respectively.

For trials that reported ethnicity, 4.7% (n = 358) were Hispanic; for acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) trials, the rates of Hispanic participation were 11.5% and 7.6%, respectively.

In terms of representation, Black patients and Asian-Pacific Islander patients had the greatest representation in CML trials at 12.7% (n = 147) and 5.3% (n = 61), respectively; and their lowest representation in chronic lymphocytic leukemia (CLL) at 3% (n = 55) and 1.1% (n = 20), respectively.

Overall, Black, Native American, and Hispanic individuals were underrepresented in the trials compared with their corresponding proportions in the general population. In acute myeloid leukemia (AML), women were also unrepresented (44.7% vs 60.5%; P < .0001), and men were underrepresented in multiple myeloma (55.3% vs 60.2%; P < .0001) and in CML (55.2% vs 62.9%; P < .0001).

“Our analysis shows that, over the past 10 years, participation in pivotal [clinical trials] investigating therapies for leukemias and [multiple myeloma] is unrepresentative of the US population,” Mycal Casey, DO, MPH, an internal medicine specialist at Medical College of Georgia at Augusta University, and co-investigators, wrote in the study. “Efforts to increase representation of minorities and disadvantaged populations in [clinical trials] should be prioritized.”

Hematologic malignancies represented approximately 10% of cancer cases and deaths in the United States. Although there have been multiple advances across the hematologic oncology space, and many new agents have consequently been approved by the FDA, study authors sought to understand whether the clinical trials informing these advances were representative of the populations most afflicted.1

Investigators reviewed 2 FDA databases—the Oncology/Hematologic Malignancies Approval Notifications, and the Novel Drug Approvals—for leukemia or multiple myeloma trials which led to a drug approval between January 1, 2022, and October 1, 2021. A total of 61 clinical trials were identified. The largest proportion of trials were for multiple myeloma, followed by CLL, and ALL.

Of the 41 trials that reported on race, 29 (70.7%) reported race data on ClinicalTrials.gov. Ethnicity data was reported in 20 (48.8%) of the 41 trials, and information regarding sex was available for 39 of the trials (95.1%). Across all the trials, patients were mostly men (54.8%) and the average age range was 41.7 to 67.3 years.

In multiple myeloma specifically, 16 out of 41 trials reported on race, this accounted for 7287 patients. Among these, 778 patients (10.7%) were Black, 339 (4.7%) were Asian-Pacific Islander, and 5852 (80.3%) were White. Half of the trials reported on ethnicity, and the percentage of Hispanic participants was 3.8% (n = 113).

AML had 5 informative trials during this period, representing 1629 patients. Among these, 3.8% were Black (n = 62), 8.8% (n = 144) were Asian-Pacific Islander, and 79.6% were White (n = 1296). Ethnicity was reported in 3 of the trials, and 6.3% (n = 75) of participants were reported to be Hispanic. White individuals accounted for 90.5% of patients (n = 1673). Ethnicity was available for 4 out of the 6 trials, and seventy participants were Hispanic (5.1%).

Four CML trials were included in the analysis. There were 1157 patients enrolled in CML trials, of which 5.3% (n = 61) were Black, 12.7% (n = 147) were Asian-Pacific Islander, and 76.7% (n = 887) were White. For ALL, there were 6 trials, with 1,119 patients. This included 25 Black patients (2.2%), 81 Asian-Pacific Islander patients (7.2%), and 886 White patients (79.2%). Two of these trials reported on ethnicity and 11.5% (n = 54) of participants were Hispanic.

These proportions were found to be significantly lower across all 5 malignancies than the corresponding SEER data. Conversely, White individuals were found to be overrepresented in trials for multiple myeloma, (80.3% vs 68.7%; P < .0001), AML (79.6% vs 77.3%; P = .0389), and CLL (90.5% vs 82.5%; P < .0001).

Moreover, participation of women was greater in multiple myeloma (44.7% vs 41.7%; P < .0001) and CML (44.7% v 39.5%, P = .0009), but under-represented in AML (44.7% vs 60.5%; P < .0001).

Geographic Distribution

The 41 trials that reported on race spanned across 990 cities, 301 (30.4%) of which were within the United States. Trials were generally cloistered in the Northeast, Southeast, and eastern side of the Midwest regions. Neither Delaware nor Wyoming had any participating cities. Multiple myeloma trials generally followed this site distribution.

AML has demonstrated county-level mortality rates nation-wide, but the Midwest states of Nebraska, South Dakota, Idaho, Minnesota, and Wisconsin did not have any sites participating in the trial. Moreover, the trial sites were primarily clustered in the Northeast, but Alabama, Mississippi, South Georgia, and the East of the Carolinas represent the counties with the highest AML mortality, low access to trials, and high minority representation.

CLL had few trials. In these trials, the count-level mortality rates were high in counties covering pats of the Midwest region, including Nebraska, South Dakota, Idaho, Minnesota, and Wisconsin. Counties located in the American Black Belt had high mortality, low trial access, and high minority representation.

The CML trials did not include representation from the Midwestern states with high county-level mortality rates and no high minority group representation. The southern counties with high mortality and minority representation were also shown to have low access to these trials.

Lastly, the ALL trials lack representation from the counties with high mortality and high minority representation across the American Black Belt, the South Appalachia region, and in Texas.

Focus on Disparities

The study authors noted that Black patients were consistently underrepresented across all the included malignancies. For example, Black individuals represent approximately 27.4% of US multiple myeloma diagnoses, yet only 4.7% were included in these multiple myeloma clinical trials. Moreover, publicly available information on ClinicalTrials.gov lacks sufficient demographic reporting. Twelve trials did not include ethnicity data even when they did provide information on race. In some trials, race was reported in a binary manor (eg, White vs other), creating ambiguity, and others provided more concise reporting.

There are efforts to diversity clinical trial representation and improve research that are underway. In 2021, ASCO released the New Equity, Diversity, and Inclusion Action plan for better representation in research. The goal of this plan is to create better concordance between research participants and disease populations, education to foster an oncology care workforce that represents the population, and to decrease barriers to care to improve care delivery.2

Similarly, in 2014, the FDA released Section 907 action Plan Inclusion of Demographic Subgroups in clinical trials. This action plan is designed to address 3 priorities, quality of data, participation improvement alleviating barriers to enrollment, and transparency of data to decrease underreporting in clinical trials. 3

Nevertheless, according to study authors, improving health care continues to represent a priority for researchers.

“There are demographic and geographic under-representations in pivotal [clinical trials] leading to drug approval for leukemias and [multiple myeloma],” study authors concluded. “Trials should represent the population with the disease and should be within reach of patients in areas of need. These disparities within cancer research need to be addressed to make results applicable to all populations.”


  1. Casey M, Odhiambo L, Aggarwal N, et al. Are pivotal clinical trials for drugs approved for leukemias and multiple myeloma representative of the population at risk? J Clin Oncol. 2022;40(32):3719-3729. doi:10.1200/JCO.22.00504
  2. ASCO unveils new equity, diversity, and inclusion action plan. American Society of Clinical Oncology. January 25, 2022. Accessed January 25, 2023. https://bit.ly/3H42OH6
  3. FDASIA Section 907: Inclusion of Demographic Subgroups in Clinical Trials. FDA. March 28, 2018. Accessed January 24, 2023. https://bit.ly/40bP31M

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