Effective bridging therapy can improve CD19 CAR-T outcomes while maintaining safety in patients with large B-cell lymphoma.

Autor:	Roddie C; Department of Haematology, University College London Hospitals, London, United Kingdom.; Research Department of Haematology, University College London Cancer Institute, University College London, London, United Kingdom., Neill L; Department of Haematology, University College London Hospitals, London, United Kingdom., Osborne W; Department of Haematology, Freeman Hospital, Newcastle, United Kingdom., Iyengar S; Department of Haematology, Royal Marsden Hospital, London, United Kingdom., Tholouli E; Department of Haematology, Manchester Royal Infirmary, Manchester, United Kingdom., Irvine D; Department of Haematology, Queen Elizabeth II Hospital, Glasgow, United Kingdom., Chaganti S; Department of Haematology, Queen Elizabeth Hospital, Birmingham, United Kingdom., Besley C; Department of Haematology, University Hospital Bristol, Bristol, United Kingdom., Bloor A; Department of Haematology, The Christie Hospital, Manchester, United Kingdom., Jones C; Department of Haematology, Cardiff University Hospital, Cardiff, United Kingdom., Uttenthal B; Department of Haematology, Addenbrookes Hospital, Cambridge, United Kingdom., Johnson R; Department of Haematology, St. James's Hospital, Leeds, United Kingdom., Sanderson R; Department of Haematology, King's College Hospital, London, United Kingdom., Cheok K; Department of Haematology, University College London Hospitals, London, United Kingdom.; Research Department of Haematology, University College London Cancer Institute, University College London, London, United Kingdom., Marzolini M; Department of Haematology, University College London Hospitals, London, United Kingdom., Townsend W; Department of Haematology, University College London Hospitals, London, United Kingdom., O'Reilly M; Department of Haematology, University College London Hospitals, London, United Kingdom., Kirkwood AA; Cancer Research United Kingdom & University College London Cancer Trials Centre, University College London Cancer Institute, University College London, London, United Kingdom., Kuhnl A; Department of Haematology, King's College Hospital, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2023 Jun 27; Vol. 7 (12), pp. 2872-2883.
DOI:	10.1182/bloodadvances.2022009019
Abstrakt:	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. (© 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.)
Databáze:	MEDLINE
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