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High pretreatment disease burden as a risk factor for infectious complications following CD19 chimeric antigen receptor T-cell therapy for large B-cell lymphoma

O'Reilly, Maeve A; Neill, Lorna; Collin, Simon M; Stone, Neil; Springell, Deborah; Mensah, Jeremy; Cheok, Kathleen PL; ... Sanderson, Robin; + view all (2024) High pretreatment disease burden as a risk factor for infectious complications following CD19 chimeric antigen receptor T-cell therapy for large B-cell lymphoma. HemaSphere , 8 (1) , Article e29. 10.1002/hem3.29. Green open access

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Abstract

Infection has emerged as the chief cause of non‐relapse mortality (NRM) post CD19‐targeting chimeric antigen receptor T‐cell therapy (CAR‐T) therapy. Even though up to 50% of patients may remain infection‐free, many suffer multiple severe, life‐threatening, or fatal infectious events. The primary aim of this study was to explore severe and life‐threatening infections post licensed CAR‐T therapy in large B‐cell lymphoma, with a focus on the role of disease burden and disease sites in assessing individual risk. We sought to understand the cohort of patients who experience ≥2 infections and those at the highest risk of infectious NRM. Our analysis identifies a higher disease burden after bridging therapy as associated with infection events. Those developing ≥2 infections emerged as a uniquely high‐risk cohort, particularly if the second (or beyond) infection occurred during an episode of immune effector cell‐associated neurotoxicity syndrome (ICANS) or while on steroids and/or anakinra for ICANS. Herein, we also describe the first reported cases of “CAR‐T cold sepsis,” a phenomenon characterized by the lack of an appreciable systemic inflammatory response at the time of detection of infection. We propose a risk‐based strategy to encourage heightened clinician awareness of cold sepsis, with a view to reducing NRM.

Type: Article
Title: High pretreatment disease burden as a risk factor for infectious complications following CD19 chimeric antigen receptor T-cell therapy for large B-cell lymphoma
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/hem3.29
Publisher version: http://dx.doi.org/10.1002/hem3.29
Language: English
Additional information: © 2024 The Authors. HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: https://discovery.ucl.ac.uk/id/eprint/10187877
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