PMID- 36724512
OWN - NLM
STAT- MEDLINE
DCOM- 20230619
LR  - 20240110
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 7
IP  - 12
DP  - 2023 Jun 27
TI  - Effective bridging therapy can improve CD19 CAR-T outcomes while maintaining 
      safety in patients with large B-cell lymphoma.
PG  - 2872-2883
LID - 10.1182/bloodadvances.2022009019 [doi]
AB  - The impact of bridging therapy (BT) on CD19-directed chimeric antigen receptor 
      T-cell (CD19CAR-T) outcomes in large B-cell lymphoma (LBCL) is poorly 
      characterized. Current practice is guided through physician preference rather 
      than established evidence. Identification of effective BT modalities and factors 
      predictive of response could improve both CAR-T intention to treat and clinical 
      outcomes. We assessed BT modality and response in 375 adult patients with LBCL in 
      relation to outcomes after axicabtagene ciloleucel (Axi-cel) or tisagenlecleucel 
      (Tisa-cel) administration. The majority of patients received BT with chemotherapy 
      (57%) or radiotherapy (17%). We observed that BT was safe for patients, with 
      minimal morbidity or mortality. We showed that complete or partial response to BT 
      conferred a 42% reduction in disease progression and death after CD19CAR-T 
      therapy. Multivariate analysis identified several factors associated with 
      likelihood of response to BT, including response to last line therapy, the 
      absence of bulky disease, and the use of polatuzumab-containing chemotherapy 
      regimens. Our data suggested that complete or partial response to BT may be more 
      important for Tisa-cel than for Axi-cel, because all patients receiving Tisa-cel 
      with less than partial response to BT experienced frank relapse within 12 months 
      of CD19CAR-T infusion. In summary, BT in LBCL should be carefully planned toward 
      optimal response and disease debulking, to improve patient outcomes associated 
      with CD19CAR-T. Polatuzumab-containing regimens should be strongly considered for 
      all suitable patients, and failure to achieve complete or partial response to BT 
      before Tisa-cel administration may prompt consideration of further lines of BT 
      where possible.
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 - Roddie, Claire
AU  - Roddie C
AUID- ORCID: 0000-0002-4901-5858
AD  - Department of Haematology, University College London Hospitals, London, United 
      Kingdom.
AD  - Research Department of Haematology, University College London Cancer Institute, 
      University College London, London, United Kingdom.
FAU - Neill, Lorna
AU  - Neill L
AD  - Department of Haematology, University College London Hospitals, London, United 
      Kingdom.
FAU - Osborne, Wendy
AU  - Osborne W
AD  - Department of Haematology, Freeman Hospital, Newcastle, United Kingdom.
FAU - Iyengar, Sunil
AU  - Iyengar S
AUID- ORCID: 0000-0003-4863-4160
AD  - Department of Haematology, Royal Marsden Hospital, London, United Kingdom.
FAU - Tholouli, Eleni
AU  - Tholouli E
AD  - Department of Haematology, Manchester Royal Infirmary, Manchester, United 
      Kingdom.
FAU - Irvine, David
AU  - Irvine D
AD  - Department of Haematology, Queen Elizabeth II Hospital, Glasgow, United Kingdom.
FAU - Chaganti, Sridhar
AU  - Chaganti S
AD  - Department of Haematology, Queen Elizabeth Hospital, Birmingham, United Kingdom.
FAU - Besley, Caroline
AU  - Besley C
AD  - Department of Haematology, University Hospital Bristol, Bristol, United Kingdom.
FAU - Bloor, Adrian
AU  - Bloor A
AUID- ORCID: 0000-0003-4550-220X
AD  - Department of Haematology, The Christie Hospital, Manchester, United Kingdom.
FAU - Jones, Ceri
AU  - Jones C
AD  - Department of Haematology, Cardiff University Hospital, Cardiff, United Kingdom.
FAU - Uttenthal, Ben
AU  - Uttenthal B
AD  - Department of Haematology, Addenbrookes Hospital, Cambridge, United Kingdom.
FAU - Johnson, Rod
AU  - Johnson R
AD  - Department of Haematology, St. James's Hospital, Leeds, United Kingdom.
FAU - Sanderson, Robin
AU  - Sanderson R
AUID- ORCID: 0000-0003-4915-2833
AD  - Department of Haematology, King's College Hospital, London, United Kingdom.
FAU - Cheok, Kathleen
AU  - Cheok K
AD  - Department of Haematology, University College London Hospitals, London, United 
      Kingdom.
AD  - Research Department of Haematology, University College London Cancer Institute, 
      University College London, London, United Kingdom.
FAU - Marzolini, Maria
AU  - Marzolini M
AD  - Department of Haematology, University College London Hospitals, London, United 
      Kingdom.
FAU - Townsend, William
AU  - Townsend W
AD  - Department of Haematology, University College London Hospitals, London, United 
      Kingdom.
FAU - O'Reilly, Maeve
AU  - O'Reilly M
AD  - Department of Haematology, University College London Hospitals, London, United 
      Kingdom.
FAU - Kirkwood, Amy A
AU  - Kirkwood AA
AD  - Cancer Research United Kingdom & University College London Cancer Trials Centre, 
      University College London Cancer Institute, University College London, London, 
      United Kingdom.
FAU - Kuhnl, Andrea
AU  - Kuhnl A
AD  - Department of Haematology, King's College Hospital, London, United Kingdom.
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 (Receptors, Chimeric Antigen)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antigens, CD19)
SB  - IM
MH  - Adult
MH  - Humans
MH  - *Receptors, Chimeric Antigen
MH  - Neoplasm Recurrence, Local
MH  - Bridge Therapy
MH  - Adaptor Proteins, Signal Transducing
MH  - Antigens, CD19/therapeutic use
MH  - *Lymphoma, Large B-Cell, Diffuse/drug therapy
PMC - PMC10300297
COIS- Conflict-of-interest disclosure: A.K., S.C., C.B, S.I., and C.R. have served on 
      advisory boards and received honoraria from Kite/Gilead, Novartis, and Bristol 
      Myers Squibb. A.A.K. received honoraria from Kite/Gilead. R.S., D.I., B.U., E.T., 
      C.J., and M.O. have served on advisory boards and received honoraria from 
      Kite/Gilead and Novartis. W.O. has served on advisory boards and received 
      honoraria from Kite/Gilead, Novartis, Bristol Myers Squibb, Janssen, Roche, 
      Servier, and Pfizer. W.T. has received honoraria and consultancy fees from Kite, 
      Bristol Myers Squibb, and Roche. The remaining authors declare no competing 
      financial interests.
EDAT- 2023/02/02 06:00
MHDA- 2023/06/19 13:08
PMCR- 2023/02/03
CRDT- 2023/02/01 17:42
PHST- 2023/01/21 00:00 [accepted]
PHST- 2022/09/26 00:00 [received]
PHST- 2023/06/19 13:08 [medline]
PHST- 2023/02/02 06:00 [pubmed]
PHST- 2023/02/01 17:42 [entrez]
PHST- 2023/02/03 00:00 [pmc-release]
AID - 494292 [pii]
AID - 10.1182/bloodadvances.2022009019 [doi]
PST - ppublish
SO  - Blood Adv. 2023 Jun 27;7(12):2872-2883. doi: 10.1182/bloodadvances.2022009019.