High pretreatment disease burden as a risk factor for infectious complications following CD19 chimeric antigen receptor T‐cell therapy for large B‐cell lymphoma
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 p...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-01-01
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| Series: | HemaSphere |
| Online Access: | https://doi.org/10.1002/hem3.29 |
| _version_ | 1797321312684736512 |
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| author | Maeve A. O'Reilly Lorna Neill Simon M. Collin Neil Stone Deborah Springell Jeremy Mensah Kathleen P. L. Cheok Katarzyna Jalowiec Reuben Benjamin Andrea Kuhnl Claire Roddie Robin Sanderson |
| author_facet | Maeve A. O'Reilly Lorna Neill Simon M. Collin Neil Stone Deborah Springell Jeremy Mensah Kathleen P. L. Cheok Katarzyna Jalowiec Reuben Benjamin Andrea Kuhnl Claire Roddie Robin Sanderson |
| author_sort | Maeve A. O'Reilly |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T04:56:46Z |
| format | Article |
| id | doaj.art-b2cae7a4b52d4e08b911dbd4be07370b |
| institution | Directory Open Access Journal |
| issn | 2572-9241 |
| language | English |
| last_indexed | 2024-03-08T04:56:46Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | HemaSphere |
| spelling | doaj.art-b2cae7a4b52d4e08b911dbd4be07370b2024-02-07T15:15:48ZengWileyHemaSphere2572-92412024-01-0181n/an/a10.1002/hem3.29High pretreatment disease burden as a risk factor for infectious complications following CD19 chimeric antigen receptor T‐cell therapy for large B‐cell lymphomaMaeve A. O'Reilly0Lorna Neill1Simon M. Collin2Neil Stone3Deborah Springell4Jeremy Mensah5Kathleen P. L. Cheok6Katarzyna Jalowiec7Reuben Benjamin8Andrea Kuhnl9Claire Roddie10Robin Sanderson11Department of Haematology University College London Hospital London UKDepartment of Haematology University College London Hospital London UKBristol Medical School University of Bristol Bristol UKDepartment of Infectious Diseases University College London Hospital London UKDepartment of Haematology University College London Hospital London UKDepartment of Haematology King's College London Hospital London UKDepartment of Haematology University College London Hospital London UKDepartment of Haematology University College London Hospital London UKDepartment of Haematology King's College London Hospital London UKDepartment of Haematology King's College London Hospital London UKDepartment of Haematology University College London Hospital London UKDepartment of Haematology King's College London Hospital London UKAbstract 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.https://doi.org/10.1002/hem3.29 |
| spellingShingle | Maeve A. O'Reilly Lorna Neill Simon M. Collin Neil Stone Deborah Springell Jeremy Mensah Kathleen P. L. Cheok Katarzyna Jalowiec Reuben Benjamin Andrea Kuhnl Claire Roddie Robin Sanderson 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 |
| 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 |
| title_full | High pretreatment disease burden as a risk factor for infectious complications following CD19 chimeric antigen receptor T‐cell therapy for large B‐cell lymphoma |
| title_fullStr | High pretreatment disease burden as a risk factor for infectious complications following CD19 chimeric antigen receptor T‐cell therapy for large B‐cell lymphoma |
| title_full_unstemmed | High pretreatment disease burden as a risk factor for infectious complications following CD19 chimeric antigen receptor T‐cell therapy for large B‐cell lymphoma |
| title_short | High pretreatment disease burden as a risk factor for infectious complications following CD19 chimeric antigen receptor T‐cell therapy for large B‐cell lymphoma |
| title_sort | high pretreatment disease burden as a risk factor for infectious complications following cd19 chimeric antigen receptor t cell therapy for large b cell lymphoma |
| url | https://doi.org/10.1002/hem3.29 |
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