Dr Riedell on Efficacy and Safety of Rapcabtagene Autoleucel in R/R DLBCL

“There are a lot of attractive features in the context that [rapcabtagene autoleucel is] associated with high efficacy and also seems like a safe product. Therefore, it might certainly have further utilization, should we see some more mature data and further follow-up of these patients. [Rapcabtagene autoleucel] may be an attractive agent to consider in this space.”

Peter Riedell, MD, associate professor of medicine, Section of Hematology/Oncology, David and Etta Jonas Center for Cellular Therapy, the University of Chicago, provides an update on the efficacy and safety outcomes of rapcabtagene autoleucel (YTB323) in the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in a phase 2 trial (NCT03960840).

Data presented at the 2024 ASH Annual Meeting demonstrated that patients (n = 63) treated with rapcabtagene autoleucel—a next-generation CD19-directed CAR T-cell therapy—produced an overall response rate (ORR) of 88.3% (95% CI, 77.4%-95.2%), which included a complete response rate of 65.0% (95% CI, 51.6%-76.9%). The primary end point of best overall response of CR was met.

Additionally, the 12-month progression-free survival (PFS) rate was 48.2% in the overall population, and the median PFS was 11.9 months (95% CI, 5.6-not evaluable [NE]). In patients who achieved a CR (n = 30), the median PFS was NE (95% CI, 14.5-NE), and the 12-month PFS rate was 79.3%.

Safety data demonstrated that any-grade cytokine release syndrome (CRS) was reported in 44.4% of patients; however, most instances were low-grade, Riedell explains. Grade 3 and grade 4 CRS each occurred in 3.2% of patients, and no grade 5 events were reported. Immune effector cell–associated neurotoxicity syndrome (ICANS) was observed at grade 1 in 3.2% of patients, grade 3 in 3.2% of patients, and grade 4 in 1.6% of patients.

Riedell explains that these findings suggest that rapcabtagene autoleucel may offer a manageable safety profile compared with other CAR T-cell therapies, which have traditionally been associated with higher rates of severe CRS and ICANS. Ongoing follow-up analyses to assess the durability of these responses will be key to further elucidate what role rapcabtagene autoleucel could play in the relapsed/refractory DLBCL treatment paradigm, he concludes.