Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
In an analysis of previous trials, CAR-T therapy showed moderate efficacy in patients with CLL, but questions remain about the durability of responses.
Who Performed the Research and Where Was it Presented:
Dr. Jaison Lawrence Alexander Santhi from Mercy Catholic Medical Center and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting in 2025.
Background:
Chimeric antigen T cell receptor (CAR-T) therapy is a cellular immune therapy that takes T cells (a type of white blood cell) from a patient’s blood and reengineers them ex vivo (outside the body) to recognize and attack cancer cells. CAR-T cell therapy has revolutionized the treatment of several B-cell cancers. Still, its clinical development for chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) has faced hurdles due to inferior response rates, higher risk of side effects, and shorter response duration compared with other B-cell cancers. For this study, researchers analyzed published clinical trials of CAR-T therapy for CLL to evaluate the overall efficacy of CAR-T therapy.
Methods and Participants:
Researchers performed a type of study known as a meta-analysis, which is basically a way of analyzing multiple studies together to get an idea of overall efficacy. Researchers identify relevant published clinical trials, synthesize the quantitative data from these studies, and analyze the combined data set. A total of six clinical trials investigating CAR-T cell therapies for CLL were included in this analysis. This study primarily included phase 1 and 2 trials.
Results:
- 262 patients from six studies were included in the analysis.
- The overall response rate (how many people had their disease shrink) was 61%.
- The complete response rate (how many people had all blood counts and lymph nodes return to normal) was 29%.
- The undetectable measurable residual disease (uMRD) rate was 71%.
- The median duration of response was 19 months.
- The median progression-free survival (how long before the disease gets worse) was 12 months.
- The median overall survival (how long patients are alive) was 43 months.
Conclusions:
The authors concluded that CAR-T therapy showed moderate efficacy based on the overall response rate and complete response rate. While the percentage of patients reaching uMRD was promising, there are questions about the durability of response, as the median progression-free survival was only 12 months. Previous research has also suggested that CAR-T works well for some patients, but it does not work for all patients.
While there are still questions about the role of CAR-T therapy in CLL, in 2024, liso-cel became the first CAR-T product approved for use in relapsed / refractory CLL / SLL, specifically for patients who have already been treated with a BTK inhibitor and a BCL2 inhibitor. An analysis of real-world data found that patients with CLL treated with liso-cel have response rates that are just as good or even higher than those seen in clinical trials. Additionally, combining liso-cel with a BTK inhibitor improved patient outcome. CAR-T therapy is an option for some patients with CLL, and we continue to learn more about the best way to use it.
Links and Resources:
You can read the actual ASH abstract here: Efficacy of CAR-T cell therapy in chronic lymphocytic leukemia: A meta-analysis
Take care of yourself first.
Ann Liu, PhD
