TY - JOUR
T1 - Product Attributes of CAR T-cell Therapy Differentially Associate with Efficacy and Toxicity in Second-line Large B-cell Lymphoma (ZUMA-7)
AU - Filosto, Simone
AU - Vardhanabhuti, Saran
AU - Canales, Miguel A.
AU - Poiré, Xavier
AU - Lekakis, Lazaros J.
AU - de Vos, Sven
AU - Portell, Craig A.
AU - Wang, Zixing
AU - To, Christina
AU - Schupp, Marco
AU - Poddar, Soumya
AU - Trinh, Tan
AU - Warren, Carmen M.
AU - Aguilar, Ethan G.
AU - Budka, Justin
AU - Cheng, Paul
AU - Chou, Justin
AU - Bot, Adrian
AU - Shen, Rhine R.
AU - Westin, Jason R.
N1 - Publisher Copyright:
© 2024 American Association for Cancer Research Inc.. All rights reserved.
PY - 2024/1
Y1 - 2024/1
N2 - 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 (LBCL) 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.
AB - 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 (LBCL) 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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U2 - 10.1158/2643-3230.BCD-23-0112
DO - 10.1158/2643-3230.BCD-23-0112
M3 - Article
C2 - 37983485
AN - SCOPUS:85181852641
SN - 2643-3230
VL - 5
SP - 21
EP - 33
JO - Blood cancer discovery
JF - Blood cancer discovery
IS - 1
ER -