Locally manufactured versus commercial CAR T therapy for large B-cell lymphoma : a multi-center propensity score-matched analysis

Abstract

Locally manufactured chimeric antigen receptor T-cell (CAR T) therapy enables rapid manufacturing and a substantially shorter vein-to-vein time. However, its clinical efficacy compared to commercial CAR T products remains unclear. This retrospective study compared outcomes in patients with Large B-cell lymphoma (LBCL) treated with a CD19-directed autologous locally manufactured CAR T product (CD28-based co-stimulation) versus axicabtagene-ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) across three academic centers. All patients had received at least two prior lines of therapy. Propensity score analysis for CAR T product adjusted for age, karnofsky performance status, lactate dehydrogenase (LDH) level, primary refractory disease, and transformed histology were performed to account for underlying differences in treatment groups. Among 330 patients (132 axi-cel, 104 tisa-cel, 94 locally manufactured), those treated with locally manufactured CAR T were younger, had higher performance status, and were more likely to present with elevated LDH and primary refractory disease. Median time from apheresis to CAR T infusion was significantly shorter with locally manufactured CAR T (11 days) than with axi-cel (38 days) or tisa-cel (44 days) (p<0.001). In adjusted analyses for progression-free survival (PFS), there was a trend to improved PFS in locally manufactured versus axi-cel (weighted hazard ratio [WHR], 1.54; 95% CI, 1.00–2.37; p=0.051) and no significant difference between locally manufactured versus tisa-cel (HR 0.71, 95% CI 0.45–1.11; p=0.13). Overall survival was comparable across groups: locally manufactured vs axi-cel (HR 1.35, 95% CI 0.87–2.10; p=0.18) and locally manufactured vs tisacel (HR 0.85, 95% CI 0.53–1.34; p=0.48). Rates of grade ≥2 cytokine release syndrome were lower with locally manufactured CAR T. These findings support locally manufactured CAR T as a clinically comparable alternative to commercial products in LBCL, with the potential advantage of rapid availability for patients with aggressive disease.