CAR-T ‘can still be an effective choice’ for patients excluded from pivotal trials
Click Here to Manage Email Alerts
Key takeaways:
- Patients who would not have been eligible for pivotal CAR-T trials may still derive benefit from the therapy.
- Efforts to improve recruitment of more diverse patients are essential.
SAN DIEGO — Patients underrepresented in pivotal trials of anti-CD19 chimeric antigen receptor T-cell therapy may still derive benefit from the treatment modality, according to a speaker at ASH Annual Meeting and Exposition.
During his talk in an ASH special interest session, Daniel Goyco Vera, MD, hematology/oncology fellow at UT Southwestern and former internal medicine resident at Baylor College of Medicine, discussed findings from a study he led that analyzed the first 61 patients with lymphoma treated with CAR T cells at Baylor College of Medicine’s Center for Cell and Gene Therapy.
Fewer than half of those individuals would have met inclusion criteria to participate in pivotal trials for commercially available CAR-T products.
However, in this small sample size, anti-CD19 CAR T-cell therapy effectively treated patients with chemotherapy-resistant diffuse large B-cell lymphoma or follicular lymphoma regardless of whether they would have been eligible for pivotal CAR-T trials.
Goyco Vera discussed how nonwhite individuals were underrepresented in pivotal trials of CAR T-cell therapies. For example, they accounted for only 11% of participants in ZUMA-1 — the pivotal trial of axicabtagene ciloleucel (Yescarta; Kite Pharma/Gilead Sciences) — even though researchers enrolled patients from several large centers.
“We can do a better job in the recruitment of underrepresented minority patients,” Goyco Vera told Healio. “We can find minority patients who will meet the medical criteria, and we’re starting to get traction addressing these things. Building trust with patients is important.”
Comparable outcomes
The study Goyco Vera led at Baylor examined CAR-T outcomes among patients with chemotherapy-refractory DLBCL or follicular lymphoma.
Baylor College of Medicine has a diverse catchment area, and about 65% of residents in its catchment area identify as underrepresented minorities, Goyco Vera said.
“Our hypothesis was that CAR-T can still be an effective choice for those patients who would have been excluded from the trials for being too sick, for example, or for being underrepresented minorities,” he said.
Of the 61 patients evaluated, 18 (30%) were Hispanic, seven (11%) were Black and five (8%) were Asian.
Only 24 (39%) patients in the analysis would have met inclusion criteria for initial CAR-T trials.
The other 37 (61%) would have been excluded. The primary reasons for exclusion would’ve been insufficient bone marrow reserve (n = 14), recent systemic or radiation therapy (n = 11) or insufficient renal function (n = 7). Sixteen of the 37 excluded patients would have been excluded based on two or more criteria.
At the time of data analysis, 37 participants (61%) had experienced disease progression and 22 (36%) had died. The researchers observed no difference between groups in rates of grade 3 or higher immune effector mediated toxicity (13% for those who met trial eligibility vs. 14% for those who did not; 10% for underrepresented minorities vs. 16% for white patients).
Although researchers found no statistical differences in PFS between those who would have and would not have met trial eligibility criteria, a lower percentage patients who would have been excluded from clinical trials achieved 1-year OS (82% for those who met criteria vs. 59% for those who did not; P = .034).
“This isn’t very surprising, since patients who would have been excluded are generally sicker and have more comorbidities,” Goyco Vera said.
Underrepresented minority patients had similar rates of PFS, as well as a similar 1-year OS rate as white patients (65% vs. 71%).
Building trust
Inclusion criteria for early-phase studies are aimed at enrolling participants whose outcomes are likely to support the approval of the drug, Goyco Vera said.
“At the beginning of drug development, the goal is to get the product approved,” he said. “If you bring in sicker people, it’s less likely those results are going to reflect good outcomes. In the real world, we have to consider that not everyone is an ideal patient.”
Similarly, trials in which minority patients are underrepresented are unlikely to capture the most accurate data about outcomes after CAR-T in these groups.
Efforts to improve recruitment of more diverse patient populations will be essential, Goyco Vera said.
He highlighted the need to address potential medical mistrust, which has deep roots in the United States due to the Tuskegee syphilis study and other examples of deception or mistreatment.
“We should be focused on building trust and acknowledging our wrongdoing,” Goyco Vera said.
Having racially concordant researchers on staff of clinical trials is another strategy that may improve recruitment, Goyco Vera said. Taking steps to overcome language barriers is a potential step.
“Especially now, in an era of so much mistrust and misinformation, people are going to trust people who have the same background as them,” Goyco Vera said. “Talking to a Hispanic patient in Spanish makes them feel more represented and understood than using a translator.”
The “resources are there” for institutions to improve the diversity of clinical trial enrollment, Goyco Vera said.
The effort required to eliminate barriers and ensure equitable access may not be easy, but it will be worth the effort, Goyco Vera added.
“We want to be able to say with certainty that these results are generalizable to the real-world population,” he said.
Reference:
- Goyco Vera D. Outcomes of patients underrepresented in pivotal trials of CAR T-cell therapy. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2024; San Diego.
- Goyco Vera D, et al. Transplant Cell Ther. 2024;doi:10.1016/j.jtct.2023.12.246.
For more information:
Daniel Goyco Vera, MD, can be reached at danielgv95@gmail.com.
Collapse
Healio Interviews
Click Here to Manage Email Alerts