Dr Lori Muffly Spotlights Disparities in Clinical Trial Enrollment, Patient Outcomes in Pediatric ALL

Lori Muffly, MD, associate professor of medicine, Blood & Marrow Transplantation, Stanford University, discusses findings of her study showing disparities in clinical trial enrollment and patient outcomes for at-risk pediatric minority populations with acute lymphoblastic leukemia (ALL).

Investment, further research, and interventions are warranted to address disparities in acute lymphoblastic leukemia (ALL) clinical trial participation that underrepresents at-risk adolescent and young adult (AYA) Hispanic and Black patients, said Lori Muffly, MD, associate professor of medicine, Blood & Marrow Transplantation, Stanford University.

Muffly is lead author of the abstract, “Enrollment Characteristics and Outcomes of Hispanic and Black AYA ALL Patients Enrolled on a U.S. Intergroup Clinical Trial: A Comparison of the CALGB 10403 (Alliance) Cohort With U.S. Population-Level Data," presented at the 63rd Annual American Society of Hematology Meeting and Exposition.


With minority populations known to be historically underrepresented in clinical trials, can you speak on the investigative targets of abstract 337 and how the study was conducted?

We made an observation that in the largest prospective trial in recent years in the United States that focused on AYAs, which was the intergroup CALGB 10403 trial that was conducted between 2008 and 2012, that the number of enrollees who were reported to be of Hispanic ethnicity was relatively low compared with what had been reported in population data, which estimates that approximately 40% or higher of AYA ALL in the United States is in Hispanic people.

That was sort of the starting point of our study. We were trying to uncover any potential explanations on anything that we could find, because we know that enrollment among different populations in this country is quite a complex topic. But we really focused in on the geographical location of trial enrollees and how the enrollment patterns on study may have impacted the low proportion of Hispanic patients.

We found that on trial, approximately 17% of the trial enrollees were reported to be Hispanic. Again, that's relative to the 42% population estimate. And so we did an analysis of the geography of AYA ALL patients per state in the United States and found that AYA ALL is most common among states in the West, the South. Texas, Florida, California are probably the big 3.

Then we looked at each state, the proportion of Hispanic AYA ALL patients, and we found a very similar pattern. California, Texas, Florida, and some other states in the South. And then we looked at where the enrollees on the trial came from. We found that the majority of the enrollees came from midwestern states, and so we mapped geographically these differences and pretty strikingly pattern recognition differences between where these Hispanic patients live and where the trial enrolled.

We came to the conclusion that likely thinking about a priori when a trial is designed, thinking about how site location may impact the distribution of different subgroups within the trial, I think, is really important.

What notable differences by race/ethnicity were observed in clinical trial participation and patient outcomes for AYAs given the pediatric-inspired ALL regimen in the study? How may findings influence future clinical trial enrollment criteria for these patient populations?

We then looked at outcomes on study based on background. So, we looked at the Hispanic AYAs enrolled on study relative to the non-Hispanic White population, which was a much larger population relative to the non-Hispanic Black AYAs who enrolled on trial. In population data in the United States, and this has been shown in a multitude of ways, in in AYA ALL, Hispanic and Black populations tend to do significantly worse than non-Hispanic White populations.

There's been a lot of reasons, including ALL biology that had been posited to explain this difference. In our study, we actually found that the Hispanic patients on trial did as well as the non-Hispanic White patients. It's difficult to compare trial data to population-based data, but the trial outcomes for the Hispanic population were better than what would be expected based on the population estimate.

So, we made a somewhat of a leap to say it's possible that if these patients can get onto clinical trials—and this was a big clinical trial and led to really a treatment change in this country for young adults—then the potential to do better is possibly there.

What efforts should be considered to improve access and uptake to cancer clinical trials in underserved communities, and what further research is warranted specific to ALL and other cancers known to have great impact on minority populations?

This is an area of great interest to me. I have been studying patterns of care and access to care in AYA ALL for a while. One of our studies from a couple of years ago, what we noted is that there's great dispersion of care for this potentially curable leukemia in this country.

So, if you're under the age of 18, about 90% of that population is treated at centers that have access to clinical trials that have designation from the Children's Oncology Group or the NCI [National Cancer Institute] as being a specialty cancer center. However, once you get over the age of 18 in the state I live in, California, that flips dramatically and over half of the patients are treated at centers that don't have ALL-specific clinical trials or readily accessible studies.

I think it speaks to sort of the patterns of treatment in this country, and I think that we need to start looking more at how outcomes differ based on where patients are treated for curable diseases in young people, because our studies in the past have shown that there is a difference in outcome. I also think that people, like investigators and companies planning clinical trials, the only way to make this geographical alignment better is to think about it in the beginning, to make it a priority. So, if you're running an ALL trial, to have some idea of what the cancer incidence is in the areas in which you're planning to open the trial, because there's no surprise that if you go to places that have very low rates of Hispanic people that your trial is not going to look like the true ALL population in this country.

I think this is a very important topic right now. I've been sitting at ASH and hearing all of these abstracts on similar topics, and I think the time is now. We need to invest in ways, research, and interventions to really change this, because there are things that we can do that are not so hard, and I think it's just time that we really [need to] invest in to make it a priority.