PMID- 38498731
OWN - NLM
STAT- Publisher
LR  - 20240406
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Linking)
DP  - 2024 Mar 18
TI  - CAR19 monitoring by peripheral blood immunophenotyping reveals histology-specific 
      expansion and toxicity.
LID - bloodadvances.2024012637 [pii]
LID - 10.1182/bloodadvances.2024012637 [doi]
AB  - Chimeric antigen receptor (CAR) T cells directed against CD19 (CAR19) are a 
      revolutionary treatment for B-cell lymphomas. CAR19 cell expansion is necessary 
      for CAR19 function but is also associated with toxicity. To define the impact of 
      CAR19 expansion on patient outcomes, we prospectively followed a cohort of 236 
      patients treated with CAR19 (brexucabtagene autoleucel or axicabtagene 
      ciloleucel) for mantle cell (MCL), follicular (FL), and large B-cell lymphoma 
      (LBCL) over the course of five years and obtained CAR19 expansion data using 
      peripheral blood immunophenotyping for 188 of these patients. CAR19 expansion was 
      higher in patients with MCL compared to other lymphoma histologic subtypes. 
      Notably, patients with MCL had increased toxicity and required four-fold higher 
      cumulative steroid doses than patients with LBCL. CAR19 expansion was associated 
      with the development of cytokine release syndrome (CRS), immune effector cell 
      associated neurotoxicity syndrome (ICANS), and the requirement for granulocyte 
      colony stimulating factor (GCSF) after day 14 post-infusion. Younger patients and 
      those with elevated lactate dehydrogenase (LDH) had significantly higher CAR19 
      expansion. In general, no association between CAR19 expansion and LBCL treatment 
      response was observed. However, when controlling for tumor burden, we found that 
      lower CAR19 expansion in conjunction with low LDH was associated with improved 
      outcomes in LBCL. In sum, this study finds CAR19 expansion principally associates 
      with CAR-related toxicity. Additionally, CAR19 expansion as measured by 
      peripheral blood immunophenotyping may be dispensable to favorable outcomes in 
      LBCL.
CI  - Copyright (c) 2024 American Society of Hematology.
FAU - Hamilton, Mark P
AU  - Hamilton MP
AD  - Stanford University, Stanford, California, United States.
FAU - Craig, Erin
AU  - Craig E
AD  - Stanford University, Stanford, California, United States.
FAU - Gentille Sanchez, Cesar
AU  - Gentille Sanchez C
AUID- ORCID: 0000-0001-7643-8154
AD  - Stanford University School of Medicine, United States.
FAU - Mina, Alain
AU  - Mina A
AD  - Stanford University School of Medicine, United States.
FAU - Tamaresis, John
AU  - Tamaresis J
AD  - Stanford University, Stanford, California, United States.
FAU - Kirmani, Nadia
AU  - Kirmani N
AUID- ORCID: 0000-0003-0723-7919
AD  - Stanford University, Stanford, California, United States.
FAU - Ehlinger, Zachary
AU  - Ehlinger Z
AD  - Stanford Cancer Institute, Stanford, California, United States.
FAU - Syal, Shriya
AU  - Syal S
AUID- ORCID: 0009-0008-6992-8815
AD  - Stanford University, Palo Alto, California, United States.
FAU - Good, Zinaida
AU  - Good Z
AUID- ORCID: 0000-0003-2343-5771
AD  - Stanford University, Stanford, California, United States.
FAU - Sworder, Brian
AU  - Sworder B
AD  - Stanford University School of Medicine, Palo Alto, California, United States.
FAU - Schroers-Martin, Joseph
AU  - Schroers-Martin J
AD  - Stanford University School of Medicine, Stanford, California, United States.
FAU - Lu, Ying
AU  - Lu Y
AUID- ORCID: 0000-0002-7698-8962
AD  - Stanford University, Stanford, California, United States.
FAU - Muffly, Lori
AU  - Muffly L
AUID- ORCID: 0000-0002-9887-6136
AD  - Stanford University, Stanford, California, United States.
FAU - Negrin, Robert S
AU  - Negrin RS
AD  - Stanford University Medical Center, Stanford, California, United States.
FAU - Arai, Sally
AU  - Arai S
AUID- ORCID: 0000-0003-1993-4172
AD  - Stanford University, Stanford, California, United States.
FAU - Lowsky, Robert
AU  - Lowsky R
AD  - Stanford University School of Medicine, Stanford (CA), Stanford, California, 
      United States.
FAU - Meyer, Everett
AU  - Meyer E
AD  - Stanford University, Stanford, California, United States.
FAU - Rezvani, Andrew R
AU  - Rezvani AR
AD  - Stanford University, Stanford, California, United States.
FAU - Shizuru, Judith A
AU  - Shizuru JA
AD  - Stanford University Medical Center, Stanford, California, United States.
FAU - Weng, Wen-Kai
AU  - Weng WK
AD  - Stanford University School of Medicine, Palo Alto, California, United States.
FAU - Shiraz, Parveen
AU  - Shiraz P
AUID- ORCID: 0000-0002-6721-0358
AD  - Stanford University, Stanford, California, United States.
FAU - Sidana, Surbhi
AU  - Sidana S
AUID- ORCID: 0000-0003-3288-7614
AD  - Stanford University, Stanford, California, United States.
FAU - Bharadwaj, Sushma
AU  - Bharadwaj S
AD  - Stanford University School of Medicine, Palo Alto, California, United States.
FAU - Smith, Melody
AU  - Smith M
AUID- ORCID: 0000-0002-2702-0381
AD  - Stanford University, Stanford, California, United States.
FAU - Dahiya, Saurabh
AU  - Dahiya S
AD  - Stanford University, Stanford, California, United States.
FAU - Sahaf, Bita
AU  - Sahaf B
AD  - Stanford University School of Medicine, United States.
FAU - Kurtz, David M
AU  - Kurtz DM
AUID- ORCID: 0000-0002-6382-4651
AD  - Stanford University, Palo Alto, California, United States.
FAU - Mackall, Crystal L
AU  - Mackall CL
AUID- ORCID: 0000-0003-0359-9023
AD  - Stanford University, Stanford, California, United States.
FAU - Tibshirani, Robert
AU  - Tibshirani R
AD  - stanford, stanford, United States.
FAU - Alizadeh, Ash A
AU  - Alizadeh AA
AUID- ORCID: 0000-0002-5153-5625
AD  - Stanford University School of Medicine, Stanford, California, United States.
FAU - Frank, Matthew J
AU  - Frank MJ
AD  - Stanford University, Stanford, California, United States.
FAU - Miklos, David B
AU  - Miklos DB
AUID- ORCID: 0000-0003-0717-4305
AD  - Stanford University Medical School, Stanford, California, United States.
LA  - eng
GR  - T15 LM007033/LM/NLM NIH HHS/United States
PT  - Journal Article
DEP - 20240318
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
SB  - IM
EDAT- 2024/03/19 00:42
MHDA- 2024/03/19 00:42
CRDT- 2024/03/18 15:13
PHST- 2024/03/07 00:00 [accepted]
PHST- 2024/01/11 00:00 [received]
PHST- 2024/03/04 00:00 [revised]
PHST- 2024/03/19 00:42 [medline]
PHST- 2024/03/19 00:42 [pubmed]
PHST- 2024/03/18 15:13 [entrez]
AID - 515342 [pii]
AID - 10.1182/bloodadvances.2024012637 [doi]
PST - aheadofprint
SO  - Blood Adv. 2024 Mar 18:bloodadvances.2024012637. doi: 
      10.1182/bloodadvances.2024012637.