Dr Riedell on the Rationale for Evaluating Rapcabtagene Autoleucel in R/R DLBCL

“In diffuse large B-cell lymphoma, CAR T-cell therapy has been heavily utilized and now adopted in the treatment paradigm. However, there are some challenges that exist in operationalizing this therapy, and one of them is we’ve seen patients have relapsed or refractory disease to CAR T-cell therapy based on components of the composition of the CAR T-cell product.”

Peter Riedell, MD, associate professor of medicine, Section of Hematology/Oncology, the University of Chicago, highlights the rationale for evaluating the CAR T-cell therapy rapcabtagene autoleucel (YTB323) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in a phase 2 study (NCT03960840).

In the DLBCL treatment paradigm, the utility of CAR T-cell therapy has been established and commonly utilized, Riedell begins. However, patients can still experience relapse and become refractory to CAR T-cell therapy, which could potentially be based on the components and composition of the CAR T-cell product, he explains. Better persistence and proliferation were associated with products enriched in stem-like T-cells, he adds.

Findings from an interim analysis of the phase 2 study presented at the 2024 ASH Annual Meeting showed that at a median follow-up of 16.4 months, data from an interim analysis in the phase 2 study demonstrated an overall response rate of 88.3% (95% CI, 77.4%-95.2%) and a complete response (CR) rate of 65.0% (95% CI, 51.6%-76.9%). Of note, CR rates at 3, 6, and 12 months were 54.6%, 56.8%, and 47.4%, respectively.

Another challenge that contributed to the rationale of the study included disease progression during the manufacturing process of the CAR T-cell product, Riedell emphasizes. He notes that the utilization of the T-charge platform helps by harvesting T-cells within 48 hours of culture and can lead to improvements in turnaround time regarding the vein-to-door time. Based on the interim analysis from the study, the median vein-to-door time was 13 days globally and 9 days in the United States, which compares favorably to other available commercial products, Riedell concludes.