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Product attributes of CAR T-cell therapy differentially associate with efficacy and toxicity in second-line large B-cell lymphoma (ZUMA-7).

Simone FilostoSaran VardhanabhutiMiguel A CanalesXavier PoireLazaros J LekakisSven de VosCraig A PortellZixing WangChristina ToMarco SchuppSoumya PoddarTan TrinhCarmen M WarrenEthan G AguilarJustin BudkaPaul ChengJustin ChouAdrian BotRhine R ShenJason R Westin
Published in: Blood cancer discovery (2023)
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.
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