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A national service for delivering CD19 CAR-Tin large B-cell lymphoma – The UK real-world experience

Research output: Contribution to journalArticlepeer-review

Andrea Kuhnl, Claire Roddie, Amy A. Kirkwood, Eleni Tholouli, Tobias Menne, Amit Patel, Caroline Besley, Sridhar Chaganti, Robin Sanderson, Maeve O'Reilly, Jane Norman, Wendy Osborne, Adrian Bloor, Sanne Lugthart, Ram Malladi, Piers E.M. Patten, Lorna Neill, Nuria Martinez-Cibrian, Hannah Kennedy, Elizabeth H. Phillips & 17 more Ceri Jones, Kirsty Sharplin, Dima El-Sharkawi, Anne Louise Latif, Amrith Mathew, Benjamin Uttenthal, Orla Stewart, Maria A.V. Marzolini, William Townsend, Kate Cwynarski, Kirit Ardeshna, Arzhang Ardavan, Kate Robinson, Antonio Pagliuca, Graham P. Collins, Roderick Johnson, Andrew McMillan

Original languageEnglish
Pages (from-to)492-502
Number of pages11
JournalBritish Journal of Haematology
Volume198
Issue number3
DOIs
Accepted/In press2022
PublishedAug 2022

Bibliographical note

Funding Information: A. K. and C. R. have served on advisory boards and received honoraria from Kite/Gilead, Novartis and Celgene/BMS. A. A. K. received honoraria from Kite/Gilead. E. T. has received speaker and consultancy fees from Novartis, Kite/Gilead, Celgene/BMS and Janssen. C. B. has served on advisory boards for Novartis and Kite/Gilead and received honoraria from Kite/Gilead, Novartis and Janssen. S. C, has served on advisory boards, provided consultancy services, and received meeting attendance support from Takeda, Novartis, Celgene/BMS, Kite/Gilead, Atara Bio, Incyte, and Roche. R. S. and M. O. have served on advisory boards and received honoraria from Kite/Gilead and Novartis. T. M has served on advisory boards and received honoraria from Kite/Gilead, Novartis, BMS, Janssen, Roche, Servier, Pfizer, Amgen. W. O. has received honoraria from Roche, Takeda, Pfizer, Servier, Kite/Gilead, MSD, Novartis, Beigene, Astra Zeneca, Syneos, Autolus, Kyowa Kirin, Abbvie, Incyte, BMS. R. M. has served on advisory boards and received honoraria from Kite/Gilead and Novartis. A. B. has received speaker fees from Novartis and conference fees from Kit/Gilead. P. E. M. P. has received research funding from Roche, Kite/Gilead, has served on advisory boards for Novartis and Abbvie, has received honoraria from Abbvie, Astra Zeneca, Gilead, Janssen, Novartis and has received support for attending meetings from Abbvie and Janssen. E. H. P. has received speaker fees from Kite/Gilead and conference fees from Celgene/BMS. D. E.‐S. has served on advisory boards for Abbvie, ASTEX, AstraZeneca, Beigene, Janssen, Kyowa Kiirin and received honoraria from Abbvie, AstraZeneca, Kite/Gilead, Janssen, Roche, Takeda and support for attending meetings from Abbvie and Novartis. A.‐L. L. has received honoraria from Kite, Jazz, Daiichi Sankyo, Novartis, Amgen, AbbVie, Astellas and participated in company‐sponsored speaker's bureau for Kite, Takeda UK, Astellas. B. U. has served on advisory boards and received conference sponsorship from Kite/Gilead, Novartis and Celgene/BMS and served on advisory boards for Atara. O. S. has received honoraria from Kite/Gilead and Novartis. W. T. has received honoraria and consultancy fees from Celgene/BMS, Incyte, and Roche. K. C. has received consultancy fees from Atara, Celgene/BMS, Kite/Gilead, Incyte, Janssen, Takeda, has participated in company‐sponsored speaker's bureau for Kite/Gilead, Incyte, Roche, Takeda, and conference fees from Celgene/BMS, Kite/Gilead, Roche and Takeda. G. P. C. has served on advisory boards and received honoraria from Kite/Gilead and Novartis. R. J. has served on advisory boards and received honoraria from Kite/Gilead and Novartis. Funding Information: The authors would like to thank the patients, their relatives and caregivers, and investigators and staff involved in this analysis. W. T. receives funding from the UCLH Biomedical Research Centre. Publisher Copyright: © 2022 British Society for Haematology and John Wiley & Sons Ltd.

King's Authors

Abstract

CD19 CAR-T have emerged as a new standard treatment for relapsed/refractory (r/r) large B-cell lymphoma (LBCL). CAR-T real-world (RW) outcomes published to date suggest significant variability across countries. We provide results of a large national cohort of patients intended to be treated with CAR-T in the UK. Consecutive patients with r/r LBCL approved for CAR-T by the National CAR-T Clinical Panel between December 2018 and November 2020 across all UK CAR-T centres were included. 404/432 patients were approved [292 axicabtagene ciloleucel (axi-cel), 112 tisagenlecleucel (tisa-cel)], 300 (74%) received the cells. 110/300 (38.3%) patients achieved complete remission (CR) at 6 months (m). The overall response rate was 77% (52% CR) for axi-cel, 57% (44% CR) for tisa-cel. The 12-month progression-free survival was 41.8% (axi-cel) and 27.4% (tisa-cel). Median overall survival for the intention-to-treat population was 10.5 m, 16.2 m for infused patients. The incidence of grade ≥3 cytokine release syndrome and neurotoxicity were 7.6%/19.6% for axi-cel and 7.9%/3.9% for tisa-cel. This prospective RW population of CAR-T eligible patients offers important insights into the clinical benefit of CD19 CAR-T in LBCL in daily practice. Our results confirm long-term efficacy in patients receiving treatment similar to the pivotal trials, but highlight the significance of early CAR-T failure.

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