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Updated: Jul 6, 2026
A Syngeneic Mouse B-Cell Lymphoma Model for Pre-Clinical Evaluation of CD19 CAR T Cells
Published on: October 16, 2018
Locally manufactured versus commercial CAR T therapy for large B-cell lymphoma: a multicenter propensity scorematched
Ronit Marcus1, Abraham Avigdor1, Uri Greenbaum2
1Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, HaShomer, Israel; School of Medicine, Faculty of Medical and Health Sciences, Aviv University, Aviv.
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 was performed to account for underlying differences in treatment groups. Among 330 patients (132 axi-cel, 104 tisa-cel, 94 locally manufactured products), 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. The 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 analysis, a trend to improved progression-free survival with axi-cel was found when comparing locally manufactured products versus axi-cel (weighted hazard ratio [WHR]=1.54; 95% confidence interval [95% CI]: 1.00-2.37; P=0.051) and no difference between those given a locally manufactured product versus tisa-cel (WHR=0.71; 95% CI: 0.45-1.11; P=0.13). Overall survival was comparable across treatment groups: locally manufactured product versus axi-cel (WHR=1.35, 95% CI: 0.87-2.10; P=0.18) and locally manufactured product versus tisa-cel (WHR=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 for LBCL, with the potential advantage of rapid availability for patients with aggressive disease.
