Potentially Modifiable Eligibility Criteria Drive Enrollment Disparities in AML Clinical Trials

Andrew Hantel, MD

Eligibility criteria for clinical trials in acute myeloid leukemia (AML) were found to disparately exclude individuals from minority populations, and some of the criteria driving these disparities were modifiable or removable, according to data from a multicenter cohort study presented at the 2024 ASCO Annual Meeting.

Andrew Hantel, MD, and colleagues evaluated data from 1283 real-world patients with newly diagnosed AML, including patients from the Non-Hispanic White population (n = 878) and patients from minoritized populations (n = 405). Findings showed that patients from minoritized populations were eligible for 6.8% fewer trials compared with the non-Hispanic White population (P < .001). Eligibility criteria such as prior malignancy (non-Hispanic White population, 22.5%; minoritized populations 17.5%; P = .04), prolonged QTc (20.5%; 12.8%; P < .001), and coronary artery disease (4.0%; 1.0%; P = .001) led to the largest disparities between the populations.

“We saw that there are a variety of criteria that are leading to [disparities in trial enrollment], adding up to these 5% to 15% differences [between non-Hispanic White and minority populations],” Hantel explained.

In an interview with OncLive^®, Hantel expanded on the goal of evaluating clinical trial eligibility criteria and their role in disparities in AML studies; discussed the importance of reevaluating eligibility criteria for future clinical trials; and highlighted the implications from this real-world study.

Hantel is an instructor in Medicine at Harvard Medical School and a faculty member in the Divisions of Leukemia and Population Sciences at Dana-Farber Cancer Institute and the HMS Center for Bioethics in Boston, Massachusetts.

OncLive: What was the rationale for evaluating eligibility criteria that contribute to racial and ethnic disparities in AML clinical trials?

Hantel: Some of our previous work looked to see if there were differences between the eligibility criteria that [have been] used in clinical trials in leukemia and the criteria that might have been put in place if those criteria were only based on the drug safety signals that we knew about at the time the trial was starting.

We previously found that there was a big gap. Trial criteria were a lot more restrictive than they needed to be, based on the known drug safety data at the time. Therefore, that provided a gap [for us to ask]: are those overly restrictive criteria leading to disparities in who's able to enroll in a clinical trial?

What methods were used during your investigation?

We took a cohort of [patients] from Dana-Farber Cancer Institute, as well as 6 other hospitals across the [greater] Chicago area, with newly diagnosed leukemia. We took those [previous trial enrollment] criteria that we knew about and applied them to that population to ask: if these were all newly diagnosed patients coming in the door, what would have happened to them? Would they have been eligible or deemed ineligible [for a trial] because of any of the criteria?

What key findings were derived from your investigation?

In this case, when we took those common criteria [from prior clinical trials] and applied them to [the study’s] population, we did see disparities by race and ethnicity, both for more intensive sets of criteria that are used for younger adults, as well as less intensive sets of criteria that are used in some of the trials for older adults. In both cases, we saw that non-Hispanic White populations had anywhere between a 5% and 20% higher likelihood of being eligible for a trial compared with minoritized groups. [The difference] varied by which [minority] group we were talking about, but [the differences were observed] across Hispanic, non-Hispanic Asian, and non-Hispanic Black [populations].

We also looked at which [eligibility] criteria seemed to be making the most difference [in terms of causing these disparities]. They varied a little bit depending on the group. Overall, there were lab values such as QTC [interval], which is one of the things that we need to check prior to somebody going on a trial, as well as prior [medical] conditions such as hepatitis B.

What are the implications of the findings from this study?

The FDA recently came out with some guidance about minimizing eligibility criteria when they don't need to be in place. [Findings from our study] are proof that there are disparities because of [these eligibility criteria]. If we're able to rationally liberalize the criteria, [without] putting patients [at risk] for any excess harm and [still] include as many people [from different] parts of the population in the studies as we can. [This will help better establish] the safety and efficacy of these drugs in the [real-world] populations they're eventually used in.

Reference

Hantel A, Wang Y, Abraham I, et al. Identifying eligibility criteria that perpetuate race/ethnic disparities in acute myeloid leukemia (AML) clinical trial participation. J Clin Oncol. 2024;42(suppl 16):1589. doi:10.1200/JCO.2024.42.16_suppl.1589