PMID- 36033121
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220830
IS  - 2155-0417 (Electronic)
IS  - 2155-0417 (Linking)
VI  - 12
IP  - 4
DP  - 2021
TI  - Efficacy and Safety of Innovative Experimental Chimeric Antigen Receptor (CAR) 
      T-cells versus Axicabtagene ciloleucel (Yescarta) for the Treatment of 
      Relapsed/Refractory Large B-Cell Lymphoma (LBCL): Matching Adjusted Indirect 
      Comparisons (MAICs) and Systematic Review.
LID - 10.24926/iip.v12i4.4345 [doi]
AB  - Despite favorable results of CAR T-cell therapy for relapsed/refractory large 
      B-cell lymphoma (R/R LBCL), several challenges remain, including incomplete 
      response, immune-mediated toxicity, and antigen-loss relapse. We delineated the 
      relative clinical benefit of the novel approaches compared to the currently 
      approved CAR T-cell therapies. In the absence of head-to-head comparisons and 
      randomized controlled trials, we performed Matching Adjusted Indirect Comparisons 
      to quantify the relative efficacy and safety of experimental CARs against 
      Axicabtagene ciloleucel (Yescarta), the first FDA-approved CAR. A total of 
      182 R/R LBCL patients from 15 clinical trials with individual patient data (IPD) 
      were pooled into eight populations by their CAR T-cell constructs and +/- ASCT 
      status. The study endpoints were Progression-Free Survival (PFS), grade >/= 3 
      cytokine release syndrome (CRS), and grade >/= 3 neurotoxicity (NT). Tandem 
      CD19.CD20.4-1BBzeta CARs indicated favorable efficacy and safety, whereas the 
      co-infusion of CD19 & CD20 with 4-1BBzeta showed no clinical benefit compared to 
      Yescarta. Third generation CD19. CD28. 4-1BBzeta, and sequential administration of 
      autologous stem cell transplantation (ASCT) and CD19. CARs presented 
      statistically insignificant yet improved PFS and safety except for ASCT combined 
      intervention which had suggestively higher NT risk than Yescarta. CARs with 
      modified co-stimulatory domains to reduce toxicity (Hu19. CD8.28Zzeta and CD19. 
      BBz.86zeta) presented remarkable safety with no severe adverse events; however, both 
      presented worse PFS than Yescarta. Third-generation CARs demonstrated 
      statistically significantly lower NT than Yescarta. CD20. 4-1BBzeta data suggested 
      targeting CD20 antigen alone lacks clinical or safety benefit compared to 
      Yescarta. Further comparisons with other FDA-approved CARs are needed.
CI  - (c) Individual authors.
FAU - Weinstein, Bayarmagnai
AU  - Weinstein B
AD  - Principles and Practice of Clinical Research (PPCR) Program, ECPE, Harvard T.H. 
      Chan School of Public Health, USA.
AD  - Department of Environmental Health Sciences, School of Public Health, University 
      at Albany, USA.
AD  - Co-first authors.
FAU - Muresan, Bogdan
AU  - Muresan B
AD  - Co-first authors.
AD  - Health Sciences Unit, University of Groningen, University Medical Center 
      Groningen, Groningen, The Netherlands.
FAU - Solano, Sara
AU  - Solano S
AD  - Principles and Practice of Clinical Research (PPCR) Program, ECPE, Harvard T.H. 
      Chan School of Public Health, USA.
FAU - de Macedo, Antonio Vaz
AU  - de Macedo AV
AD  - Principles and Practice of Clinical Research (PPCR) Program, ECPE, Harvard T.H. 
      Chan School of Public Health, USA.
AD  - Hematology Clinic, Hospital da Policia Militar, Belo Horizonte, MG, CEP, Brazil.
FAU - Lee, YoonJung
AU  - Lee Y
AD  - Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University 
      Health Sciences Center, USA.
FAU - Su, Yu-Chen
AU  - Su YC
AD  - Inari Medical, Biostatistics and Programming Dept, USA.
FAU - Ahn, Yeseul
AU  - Ahn Y
AD  - Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University 
      Health Sciences Center, USA.
AD  - These authors contributed equally to this work.
FAU - Henriquez, Gabriela
AU  - Henriquez G
AD  - These authors contributed equally to this work.
AD  - Principles and Practice of Clinical Research (PPCR) Program, ECPE, Harvard T.H. 
      Chan School of Public Health, USA.
AD  - Iberoamerican University, Santo Domingo 10203, Dominican Republic.
FAU - Camargo, Cristina
AU  - Camargo C
AD  - School of Medicine, Univesida de Sao Paulo, Brazil.
FAU - Kim, Gwang-Jin
AU  - Kim GJ
AD  - Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of 
      Medicine, University of Freiburg, Germany.
FAU - Carpenter, David O
AU  - Carpenter DO
AD  - Department of Environmental Health Sciences, School of Public Health, University 
      at Albany, USA.
AD  - Institute for Health and the Environment, University at Albany, Rensselaer, NY, 
      USA.
LA  - eng
PT  - Journal Article
DEP - 20210922
PL  - United States
TA  - Innov Pharm
JT  - Innovations in pharmacy
JID - 101574764
PMC - PMC9401376
OTO - NOTNLM
OT  - Axicabtagene ciloleucel (Yescarta)
OT  - Chimeric Antigen Receptor (CAR)
OT  - Comparative Effectiveness Study
OT  - Diffuse Large B Cell Lymphoma (DLBCL)
OT  - Lymphoma
OT  - Matching Adjusted Indirect Comparison
OT  - Systematic Literature Review
EDAT- 2022/08/30 06:00
MHDA- 2022/08/30 06:01
PMCR- 2021/09/22
CRDT- 2022/08/29 04:50
PHST- 2022/08/29 04:50 [entrez]
PHST- 2022/08/30 06:00 [pubmed]
PHST- 2022/08/30 06:01 [medline]
PHST- 2021/09/22 00:00 [pmc-release]
AID - 10.24926/iip.v12i4.4345 [doi]
PST - epublish
SO  - Innov Pharm. 2021 Sep 22;12(4):10.24926/iip.v12i4.4345. doi: 
      10.24926/iip.v12i4.4345. eCollection 2021.