PMID- 35439292
OWN - NLM
STAT- MEDLINE
DCOM- 20230306
LR  - 20230317
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 7
IP  - 5
DP  - 2023 Mar 14
TI  - HLA-DR expression on monocytes and outcome of anti-CD19 CAR T-cell therapy for 
      large B-cell lymphoma.
PG  - 744-755
LID - 10.1182/bloodadvances.2021006563 [doi]
AB  - Despite their unprecedented success in relapsed/refractory (R/R) large B-cell 
      lymphoma (LBCL), anti-CD19 CAR T cells are associated with significant toxicity, 
      and more than half of patients relapse. As monocytes emerged as key players in 
      CAR therapy, we sought to evaluate the evolution of HLA-DR expression on 
      monocytes (mHLA-DR) before and after commercial anti-CD19 CAR T-cell infusion in 
      a large cohort (n = 103) of patients with R/R LBCL and its association with 
      adverse events and treatment response. Cy-Flu-based lymphodepletion (LD) 
      upregulated mHLA-DR in 79% of the cases, whereas in 2l% of cases (15 patients), 
      the mHLA-DR level decreased after LD, and this decrease was associated with 
      poorer outcome. Low mHLA-DR at day minus 7 (D-7) (<13 500 antibodies per cell) 
      before CAR T-cell infusion correlated with older age, poorer performance status, 
      higher tumor burden, and elevated inflammatory markers. With a median follow-up 
      of 7.4 months, patients with low mHLA-DR D-7 exhibited a poorer duration of 
      response and survival than the higher mHLA-DR D-7 group. For toxicity management, 
      tocilizumab was more frequently used in the low-mHLA-DR D-7 group. These data 
      suggest that monocyte dysregulation before LD, characterized by the 
      downregulation of mHLA-DR, correlates with an inflammatory and immunosuppressive 
      tumor environment and is associated with failure of anti-CD19 CAR T cells in 
      patients with R/R LBCL. Modulation of these myeloid cells represents a promising 
      field for improving CAR therapy.
CI  - (c) 2023 by The American Society of Hematology. Licensed under Creative Commons 
      Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), 
      permitting only noncommercial, nonderivative use with attribution. All other 
      rights reserved.
FAU - Bourbon, Estelle
AU  - Bourbon E
AD  - Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, 
      Pierre-Benite, France.
AD  - Universite Claude Bernard-Lyon 1, Lyon, France.
FAU - Sesques, Pierre
AU  - Sesques P
AUID- ORCID: 0000-0001-8264-822X
AD  - Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, 
      Pierre-Benite, France.
AD  - Universite Claude Bernard-Lyon 1, Lyon, France.
FAU - Gossez, Morgane
AU  - Gossez M
AUID- ORCID: 0000-0003-1930-8956
AD  - Universite Claude Bernard-Lyon 1, Lyon, France.
AD  - Department of Clinical Immunology, Hospices Civils de Lyon, Edouard Herriot 
      Hospital, Lyon, France.
AD  - Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Centre 
      National de la Recherche Scientifique (CNRS), Unite Mixte de Recherche (UMR) 
      5308, Ecole Normale Superieure de Lyon, Universite Claude Bernard-Lyon 1, Lyon, 
      France.
FAU - Tordo, Jeremie
AU  - Tordo J
AUID- ORCID: 0000-0003-4934-283X
AD  - Department of Nuclear Medicine, Hospices Civils de Lyon, Lyon Sud Hospital, Lyon, 
      France.
FAU - Ferrant, Emmanuelle
AU  - Ferrant E
AD  - Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, 
      Pierre-Benite, France.
FAU - Safar, Violaine
AU  - Safar V
AD  - Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, 
      Pierre-Benite, France.
FAU - Wallet, Florent
AU  - Wallet F
AUID- ORCID: 0000-0003-3174-6246
AD  - Department of Critical Care, Hospices Civils de Lyon, Lyon Sud Hospital, Lyon, 
      France.
FAU - Aussedat, Guillaume
AU  - Aussedat G
AD  - Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, 
      Pierre-Benite, France.
AD  - Universite Claude Bernard-Lyon 1, Lyon, France.
FAU - Maarek, Alizee
AU  - Maarek A
AD  - Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, 
      Pierre-Benite, France.
AD  - Universite Claude Bernard-Lyon 1, Lyon, France.
FAU - Bouafia, Fadhela
AU  - Bouafia F
AD  - Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, 
      Pierre-Benite, France.
FAU - Karlin, Lionel
AU  - Karlin L
AD  - Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, 
      Pierre-Benite, France.
FAU - Ghergus, Dana
AU  - Ghergus D
AD  - Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, 
      Pierre-Benite, France.
FAU - Golfier, Camille
AU  - Golfier C
AD  - Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, 
      Pierre-Benite, France.
AD  - Universite Claude Bernard-Lyon 1, Lyon, France.
FAU - Lequeu, Helene
AU  - Lequeu H
AD  - Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, 
      Pierre-Benite, France.
FAU - Lazareth, Anne
AU  - Lazareth A
AD  - Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, 
      Pierre-Benite, France.
FAU - Schwiertz, Verane
AU  - Schwiertz V
AUID- ORCID: 0000-0002-6521-8815
AD  - Department of Pharmacy, Hospices Civils de Lyon, Lyon Sud Hospital, Lyon, France.
FAU - Viel, Sebastien
AU  - Viel S
AUID- ORCID: 0000-0002-5085-443X
AD  - Universite Claude Bernard-Lyon 1, Lyon, France.
AD  - Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Centre 
      National de la Recherche Scientifique (CNRS), Unite Mixte de Recherche (UMR) 
      5308, Ecole Normale Superieure de Lyon, Universite Claude Bernard-Lyon 1, Lyon, 
      France.
AD  - Department of Biological Immunology, Hospices Civils de Lyon, Lyon Sud Hospital, 
      Lyon, France.
FAU - Idlhaj, Maryam
AU  - Idlhaj M
AD  - Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, 
      Pierre-Benite, France.
FAU - Ghesquieres, Herve
AU  - Ghesquieres H
AD  - Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, 
      Pierre-Benite, France.
AD  - Universite Claude Bernard-Lyon 1, Lyon, France.
AD  - EA LIB (Lymphoma Immunobiology), Universite Claude Bernard-Lyon 1, Lyon, France.
FAU - Monneret, Guillaume
AU  - Monneret G
AUID- ORCID: 0000-0002-9961-5739
AD  - Universite Claude Bernard-Lyon 1, Lyon, France.
AD  - Department of Clinical Immunology, Hospices Civils de Lyon, Edouard Herriot 
      Hospital, Lyon, France.
FAU - Bachy, Emmanuel
AU  - Bachy E
AUID- ORCID: 0000-0003-2694-7510
AD  - Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, 
      Pierre-Benite, France.
AD  - Universite Claude Bernard-Lyon 1, Lyon, France.
AD  - EA LIB (Lymphoma Immunobiology), Universite Claude Bernard-Lyon 1, Lyon, France.
FAU - Venet, Fabienne
AU  - Venet F
AUID- ORCID: 0000-0003-0462-4235
AD  - Universite Claude Bernard-Lyon 1, Lyon, France.
AD  - Department of Clinical Immunology, Hospices Civils de Lyon, Edouard Herriot 
      Hospital, Lyon, France.
AD  - Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Centre 
      National de la Recherche Scientifique (CNRS), Unite Mixte de Recherche (UMR) 
      5308, Ecole Normale Superieure de Lyon, Universite Claude Bernard-Lyon 1, Lyon, 
      France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 0 (HLA-DR Antigens)
SB  - IM
MH  - Humans
MH  - *Monocytes
MH  - Immunotherapy, Adoptive/adverse effects
MH  - Neoplasm Recurrence, Local
MH  - HLA-DR Antigens
MH  - *Lymphoma, Large B-Cell, Diffuse/therapy
PMC - PMC9989525
COIS- Conflict-of-interest disclosure: P.S. received honoraria from and served in 
      advisory and consultancy roles for Janssen, Roche, Novartis and Kite/Gilead. E.F. 
      received honoraria from and served in advisory and consultancy roles for 
      Kite/Gilead, Janssen, and AbbVie. V.S. received honoraria from Roche. F.W. 
      received honoraria from and served in advisory and consultancy roles for Novartis 
      and Kite/Gilead. E. Bachy received honoraria from and served as a consultant for 
      Gilead, Novartis, Roche, Amgen, Janssen, Sanofi, and AbbVie. H. Ghesquieres 
      received honoraria from and served in advisory and consultancy roles for Gilead 
      Sciences, Celgene, Roche, Janssen, and Takeda. The remaining authors declare no 
      competing financial interests.
EDAT- 2022/04/20 06:00
MHDA- 2023/03/07 06:00
PMCR- 2022/04/20
CRDT- 2022/04/19 17:11
PHST- 2022/03/29 00:00 [accepted]
PHST- 2021/08/11 00:00 [received]
PHST- 2022/04/20 06:00 [pubmed]
PHST- 2023/03/07 06:00 [medline]
PHST- 2022/04/19 17:11 [entrez]
PHST- 2022/04/20 00:00 [pmc-release]
AID - 484970 [pii]
AID - 10.1182/bloodadvances.2021006563 [doi]
PST - ppublish
SO  - Blood Adv. 2023 Mar 14;7(5):744-755. doi: 10.1182/bloodadvances.2021006563.