Locally manufactured versus commercial CAR T therapy for large B-cell lymphoma : a multi-center propensity score-matched analysis
Year: 2025
Type: article
Study design: Observational Study
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.
Source: Haematologica
Authors: Ronit Marcus, Abraham Avigdor, Uri Greenbaum, Samantha Brown, Shalev Fried, Noa Golan-Accav, Noga Shem-Tov, Ronit Yerushalmi, Ivetta Danylesko, Elad Jacoby, Arnon Nagler, Avichai Shimoni, Orit Itzhaki, Jonathan Esensten, Ori Ben Valid, Annamaria Ballweg, Xavier Deschênes-Simard, Efrat Luttwak, Gunjan Shah, Michael Scordo, Parastoo Dahi, Miguel-Angel Perales, Tsila Zuckerman, Sean M. Devlin, Dana Yehudai-Ofir, Hazim Khatib, Nivin Shibly, Roni Shouval, Ofrat Beyar-Katz
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,157
OpenAlex ID: W7117151602
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