PMID- 37983485
OWN - NLM
STAT- MEDLINE
DCOM- 20240109
LR  - 20240229
IS  - 2643-3249 (Electronic)
IS  - 2643-3230 (Print)
IS  - 2643-3230 (Linking)
VI  - 5
IP  - 1
DP  - 2024 Jan 8
TI  - Product Attributes of CAR T-cell Therapy Differentially Associate with Efficacy 
      and Toxicity in Second-line Large B-cell Lymphoma (ZUMA-7).
PG  - 21-33
LID - 10.1158/2643-3230.BCD-23-0112 [doi]
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. SIGNIFICANCE: In ZUMA-7, the largest randomized CAR 
      T-cell trial in LBCL, a naive T-cell product phenotype (CCR7+CD45RA+) expressing 
      CD27 and CD28 associated with improved efficacy, decreased toxicity, and a lower 
      number of prior therapies, supporting earlier intervention with CAR T-cell 
      therapy. In addition, targets for improvement of therapeutic index are proposed. 
      This article is featured in Selected Articles from This Issue, p. 4.
CI  - (c)2023 The Authors; Published by the American Association for Cancer Research.
FAU - Filosto, Simone
AU  - Filosto S
AUID- ORCID: 0000-0002-7854-998X
AD  - Kite, a Gilead Company, Santa Monica, California.
FAU - Vardhanabhuti, Saran
AU  - Vardhanabhuti S
AUID- ORCID: 0000-0003-1558-2755
AD  - Kite, a Gilead Company, Santa Monica, California.
FAU - Canales, Miguel A
AU  - Canales MA
AUID- ORCID: 0000-0002-6550-2621
AD  - Clinica Universidad de Navarra, Pamplona, Spain.
FAU - Poire, Xavier
AU  - Poire X
AUID- ORCID: 0000-0003-1897-0227
AD  - Cliniques Universitaires St-Luc, Brussels, Belgium.
FAU - Lekakis, Lazaros J
AU  - Lekakis LJ
AUID- ORCID: 0009-0008-2077-7032
AD  - Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, 
      Florida.
FAU - de Vos, Sven
AU  - de Vos S
AUID- ORCID: 0000-0002-6715-4851
AD  - David Geffen School of Medicine, University of California Los Angeles, Los 
      Angeles, California.
FAU - Portell, Craig A
AU  - Portell CA
AUID- ORCID: 0000-0002-9487-8345
AD  - University of Virginia, Charlottesville, Virginia.
FAU - Wang, Zixing
AU  - Wang Z
AUID- ORCID: 0000-0002-3127-5280
AD  - Kite, a Gilead Company, Santa Monica, California.
FAU - To, Christina
AU  - To C
AUID- ORCID: 0000-0001-7164-8072
AD  - Kite, a Gilead Company, Santa Monica, California.
FAU - Schupp, Marco
AU  - Schupp M
AUID- ORCID: 0009-0007-5881-6765
AD  - Kite, a Gilead Company, Santa Monica, California.
FAU - Poddar, Soumya
AU  - Poddar S
AUID- ORCID: 0000-0002-9758-8722
AD  - Kite, a Gilead Company, Santa Monica, California.
FAU - Trinh, Tan
AU  - Trinh T
AUID- ORCID: 0009-0000-8980-3579
AD  - Kite, a Gilead Company, Santa Monica, California.
FAU - Warren, Carmen M
AU  - Warren CM
AUID- ORCID: 0009-0008-4421-9182
AD  - Kite, a Gilead Company, Santa Monica, California.
FAU - Aguilar, Ethan G
AU  - Aguilar EG
AUID- ORCID: 0000-0002-3600-0913
AD  - Kite, a Gilead Company, Santa Monica, California.
FAU - Budka, Justin
AU  - Budka J
AUID- ORCID: 0000-0003-0908-1508
AD  - Kite, a Gilead Company, Santa Monica, California.
FAU - Cheng, Paul
AU  - Cheng P
AUID- ORCID: 0000-0002-9436-7764
AD  - Kite, a Gilead Company, Santa Monica, California.
FAU - Chou, Justin
AU  - Chou J
AUID- ORCID: 0000-0002-7310-3225
AD  - Kite, a Gilead Company, Santa Monica, California.
FAU - Bot, Adrian
AU  - Bot A
AUID- ORCID: 0009-0006-3137-2271
AD  - Kite, a Gilead Company, Santa Monica, California.
FAU - Shen, Rhine R
AU  - Shen RR
AUID- ORCID: 0009-0000-8883-0727
AD  - Kite, a Gilead Company, Santa Monica, California.
FAU - Westin, Jason R
AU  - Westin JR
AUID- ORCID: 0000-0002-1824-2337
AD  - The University of Texas MD Anderson Cancer Center, Houston, Texas.
LA  - eng
GR  - N/A/
PT  - Journal Article
PL  - United States
TA  - Blood Cancer Discov
JT  - Blood cancer discovery
JID - 101764786
RN  - 0 (CD28 Antigens)
RN  - 0 (Receptors, CCR7)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
SB  - IM
MH  - Humans
MH  - *Immunotherapy, Adoptive/adverse effects
MH  - CD28 Antigens
MH  - Receptors, CCR7
MH  - *Lymphoma, Large B-Cell, Diffuse/therapy
MH  - Research Personnel
MH  - Cytokine Release Syndrome
MH  - Leukocyte Common Antigens
PMC - PMC10772511
EDAT- 2023/11/20 18:44
MHDA- 2024/01/09 06:42
PMCR- 2023/11/17
CRDT- 2023/11/20 15:02
PHST- 2023/06/30 00:00 [received]
PHST- 2023/10/05 00:00 [revised]
PHST- 2023/11/17 00:00 [accepted]
PHST- 2024/01/09 06:42 [medline]
PHST- 2023/11/20 18:44 [pubmed]
PHST- 2023/11/20 15:02 [entrez]
PHST- 2023/11/17 00:00 [pmc-release]
AID - 732332 [pii]
AID - BCD-23-0112 [pii]
AID - 10.1158/2643-3230.BCD-23-0112 [doi]
PST - ppublish
SO  - Blood Cancer Discov. 2024 Jan 8;5(1):21-33. doi: 10.1158/2643-3230.BCD-23-0112.