CAR-T safe, effective for large B-cell lymphoma regardless of race or ethnicity
Click Here to Manage Email Alerts
CHICAGO — Axicabtagene ciloleucel exhibited comparable efficacy and safety for large B-cell lymphoma regardless of patients’ race or ethnicity, according to study results presented at ASCO Annual Meeting.
Data from a real-world analysis revealed some disparities in objective and complete response rates but no statistically significant differences in measures of treatment durability for this chimeric antigen receptor T-cell therapy.
Background
Thousands of patients with large B-cell lymphoma have been treated with axicabtagene ciloleucel (Yescarta, Kite Pharma/Gilead), often called axi-cel. However, limited data are available on treatment outcomes based on race or ethnicity, according to Frederick L. Locke, MD, co-leader of the immune-oncology program and vice chair of the department of blood and marrow transplant and cellular immunotherapy at Moffitt Cancer Center and member of the Healio | Cell Therapy Next Peer Perspective Board.
“Clinical trials that led to FDA approval of the therapy were based on a relatively small number of patients, which makes it difficult to draw any conclusions about the efficacy of the treatment in different populations,” Locke told Healio. "We looked to the [Center for International Blood & Marrow Transplant Research (CIBMTR)] Cellular Immunotherapy Data Resource — which oversees the post-approval safety study for commercial axi-cel — to determine outcomes based on race and ethnicity.”
Methodology
Locke and colleagues collected data from the post-authorization safety study on 1,389 patients (81% white, 11% Hispanic/Latino, 6% Asian and 5% Black) who received axi-cel for diffuse large B-cell lymphoma between October 2017 and August 2020.
Black patients trended to be younger than white patients (median age, 55.5 years vs. 62.8 years) and more likely to have pulmonary dysfunction (41% vs 28%). A higher percentage of Black patients than white patients received axi-cel 1 year or more after their diagnosis (71% vs. 59%).
Median follow-up was 12.7 months, with a data cutoff date of June 22, 2021. The response rate analysis included patients with at least 180 days of follow-up.
Key findings
Results showed no statistically significant differences in 12-month OS or PFS based on patients’ race or ethnicity.
White patients had the highest ORR (74%), followed by Hispanic/Latino (73%), Asian (67%) and Black patients (57%).
White patients achieved the highest complete response rate (57%), followed by Hispanic/Latino (55%), Asian (53%) and Black patients (45%).
A multivariate analysis showed Black patients had inferior ORRs (OR = 0.4; 95% CI, 0.24-0.69) and complete response rates (OR = 0.55; 95% CI 0.32-0.93) compared with white patients.
Asian patients achieved longer median duration of response than white patients (HR = 0.46; 95% CI 0.24-0.87) and Black patients (HR = 0.39; 95% CI 0.17-0.88).
Hispanic/Latino patients exhibited a lower risk for grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS) than non-Hispanic patients (OR = 0.51; 95% CI, 0.31-0.85). Likewise, Asian patients exhibited a lower risk for grade 3 or higher ICANS than white patients (OR = 0.52; 95% CI, 0.29-0.96).
Clinical implications
Locke said the goal of novel therapies is to extend OS and PFS, so he found the similar results across study groups encouraging. However, he noted more study is needed to determine why overall and complete response rates varied according to race in both numerical and multivariate analyses, and what if any biologic or socioeconomic factors may have contributed to the differences.
“For patients who have access to CAR T-cell therapy, the results are generally consistent for those who receive axicabtagene ciloleucel for diffuse large B-cell lymphoma, regardless of race or ethnicity,” Locke told Healio.
“The lower response rates in African-Americans warrants further investigation into the disease biology and immune state of patients with diffuse large B-cell lymphoma based on race and ethnicity,” he added. “Further analysis should focus on access to care to determine who isn't receiving this type of therapy when they should have.”
Perspective
Back to Top
Although there are many metrics to determine the clinical efficacy of a treatment, perhaps the most important one is survival. The results presented by Locke and colleagues suggest that — thus far — survival after CAR T-cell therapy is similar regardless of a patient's race or ethnicity. Longer follow-up of these patients will be needed to confirm, but so far, the lack of any disparity in survival is the key take-home message from this study.
Mount Sinai's geographic location in the greater New York City metro area means that we provide patients of diverse backgrounds with this type of therapy, and the results presented by Locke and colleagues line up quite well with what we have anecdotally observed: this type of therapy provides great benefit across all racial and ethnic groups. The remarkable efficacy of axi-cel shown across racial and ethnic groups in this study should reaffirm a push to provide CAR-T to all patients. There are some therapies that demonstrate different efficacy in a particular racial or ethnic group, but that does not appear to be the case for axi-cel.
Because some of the surrogate clinical endpoints in this analysis show differences for some groups, another year or so of follow-up would be optimal to confirm the overall survival results remain consistent across racial and ethnic groups.
Collapse
Locke FL, et al. Abstract 7571. Presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago.
Click Here to Manage Email Alerts