Publicaciones científicas
Product attributes of CAR T-cell therapy differentially associate with efficacy and toxicity in second-line large B-cell lymphoma (ZUMA-7)
Simone Filosto 1 , Saran Vardhanabhuti 2 , Miguel A Canales 3 , Xavier Poire 4 , Lazaros J Lekakis 5 , Sven de Vos 6 , Craig A Portell 7 , Zixing Wang 1 , Christina To 1 , Marco Schupp 1 , Soumya Poddar 8 , Tan Trinh 1 , Carmen M Warren 9 , Ethan G Aguilar 8 , Justin Budka 8 , Paul Cheng 10 , Justin Chou 8 , Adrian Bot 11 , Rhine R Shen 8 , Jason R Westin 12
Abstract
Treatment resistance and toxicities remain a risk following chimeric antigen receptor (CAR) T-cell therapy. Herein, we report pharmacokinetics, pharmacodynamics, and product and apheresis attributes associated with outcomes among patients with relapsed/refractory large B-cell lymphoma treated with axicabtagene ciloleucel (axi-cel) in ZUMA-7. Axi-cel peak expansion associated with clinical response and toxicity, but not response durability.
In apheresis material and final product, a naive T-cell phenotype (CCR7+CD45RA+) expressing CD27 and CD28 associated with improved response durability, event-free survival, progression-free survival, and a lower number of prior therapies.
This phenotype was not associated with high-grade cytokine release syndrome (CRS) or neurologic events. Higher baseline and postinfusion levels of serum inflammatory markers associated with differentiated/effector products, reduced efficacy, and increased CRS and neurologic events, thus suggesting targets for intervention.
These data support better outcomes with earlier CAR T-cell intervention and may improve patient care by informing on predictive biomarkers and development of next-generation products.
CITA DEL ARTÍCULO Blood Cancer Discov. 2023 Nov 20. doi: 10.1158/2643-3230.BCD-23-0112.
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