medwireNews: A single dose of rapcabtagene autoleucel has achieved “high response rates” over a median 16 months of follow-up in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), say researchers.
Findings from the interim analysis of a phase 2 trial were presented in a poster at the EHA2025 Congress in Milan, Italy, by Mi Kwon, from Hospital General Universitario Gregorio in Marañón, Madrid, Spain, and colleagues.
“Rapcabtagene autoleucel [YTB323] is a next-generation CD19-directed chimeric antigen receptor (CAR) T-cell therapy that utilizes the T-chargeTM [Novartis, Basel, Switzerland] platform to preserve T-cell stemness by rapidly manufacturing product (<2 days),” the researchers explain.
Among 63 patients (median age 64 years) who received a single infusion of 12.5 x 106 cells of the therapy, 60 patients were followed up for at least 28 days, with an overall response rate at 12 months of 88.3% and a complete response (CR) rate of 65.0%.
The investigators note that the “responses were durable,” with a median duration of 15.2 months, and CR rates at 3, 6, and 12 months of 55%, 57%, and 47%, respectively.
Moreover, most subgroups of patients achieved a CR at 3 months, including 89% of 19 patients with prior hematopoietic cell transplant; 64% of 29 patients older than 65 years, 53% of 17 who had received at least three prior therapies; 46% of 24 patients with an International Prognostic Index (IPI) score of 3 or more points; 46% of 13 individuals refractory to all prior lines of treatment; and 44% of 26 patients who relapsed after their last line of therapy.
However, the 27 patients with a lactate dehydrogenase level above the upper limit of normal before infusion had a lower CR rate than other participants, at 29%.
Median progression-free survival (PFS) for the full study group was 11.9 months, with PFS unreached in those with a CR after 3 months of follow-up. The corresponding 12-month PFS rates in these groups were 48.2% and 79.9%.
Median overall survival (OS) was unreached in the full study population and in those with a CR at 3 months, and the respective 12-month OS rates were 83% and 100%.
Kwon and colleagues note that 60.3% of patients received bridging therapy before CAR-T cell therapy.
Forty-four percent of patients received low-dose fludarabine plus cyclophosphamide lymphodepletion (LD, 25/50 mg/m2 for 3 days) and 52.4% received high-dose LD (30/500 mg/m2 for 3 days).
Patients given low-dose LD had better CR rates than those given high-dose LD after both 3 months (61 vs 44%) and 6 months (61 vs 47%) of follow-up.
However, there were “notable differences” between the low-dose and high-dose LD groups at baseline, the researchers say, including the proportion of patients who were at least 65 years old (57 vs 36%), had elevated lactate dehydrogenase (36 vs 49%), had an IPI score of at least 3 points (43 vs 30%), and who were refractory to last therapy (57 vs 61%).
Overall, 84% of patients had grade 3 or more severe adverse events including neutropenia (62%), anemia (33%), infection (27%), thrombocytopenia (25%), and lymphopenia (16%), but “low rates” of cytokine release syndrome (CRS; 6%), and immune effector cell-associated neurotoxicity syndrome (ICANS; 5%), the investigators point out.
There were six deaths from disease progression and six deaths from adverse events, none of which were considered related to the study treatment.
Patients given low-dose LD had a lower rate of grade 3 and more severe CRS than their high-dose LD counterparts (4 vs 9%) and a comparable rate of neutropenia (68 vs 67%), but higher rates of infection (32 vs 24%) and ICANS (7 vs 3%).
“Risk-benefit analyses support use of the lower-dose LD regimen before infusion,” comment Kwon et al.
The investigators conclude that “rapcabtagene autoleucel showed promising efficacy and a favorable safety profile,” adding that “continued assessment of long-term efficacy and safety outcomes is needed.”
