| Online-Ressource |
Verfasst von: | Locke, Frederick [VerfasserIn]  |
| Filosto, Simone [VerfasserIn]  |
| Chou, Justin [VerfasserIn]  |
| Vardhanabhuti, Saran [VerfasserIn]  |
| Perbost, Regis [VerfasserIn]  |
| Dreger, Peter [VerfasserIn]  |
| Hill, Brian T. [VerfasserIn]  |
| Lee, Catherine [VerfasserIn]  |
| Zinzani, Pier L. [VerfasserIn]  |
| Kröger, Nicolaus [VerfasserIn]  |
| López-Guillermo, Armando [VerfasserIn]  |
| Greinix, Hildegard [VerfasserIn]  |
| Zhang, Wangshu [VerfasserIn]  |
| Tiwari, Gayatri [VerfasserIn]  |
| Budka, Justin [VerfasserIn]  |
| Marincola, Francesco M. [VerfasserIn]  |
| To, Christina [VerfasserIn]  |
| Mattie, Mike [VerfasserIn]  |
| Schupp, Marco [VerfasserIn]  |
| Cheng, Paul [VerfasserIn]  |
| Bot, Adrian [VerfasserIn]  |
| Shen, Rhine [VerfasserIn]  |
| Bedognetti, Davide [VerfasserIn]  |
| Miao, Harry [VerfasserIn]  |
| Galon, Jérôme [VerfasserIn]  |
Titel: | Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma |
Verf.angabe: | Frederick L. Locke, Simone Filosto, Justin Chou, Saran Vardhanabhuti, Regis Perbost, Peter Dreger, Brian T. Hill, Catherine Lee, Pier L. Zinzani, Nicolaus Kröger, Armando López-Guillermo, Hildegard Greinix, Wangshu Zhang, Gayatri Tiwari, Justin Budka, Francesco M. Marincola, Christina To, Mike Mattie, Marco Schupp, Paul Cheng, Adrian Bot, Rhine Shen, Davide Bedognetti, Harry Miao & Jérôme Galon |
E-Jahr: | 2024 |
Jahr: | February 2024 |
Umfang: | 29 S. |
Fussnoten: | Online veröffentlicht: 17. Januar 2024 ; Gesehen am 10.05.2024 |
Titel Quelle: | Enthalten in: Nature medicine |
Ort Quelle: | [New York, NY] : Springer Nature, 1995 |
Jahr Quelle: | 2024 |
Band/Heft Quelle: | 30(2024), Heft 2, S. 507-518, 11 gezählte sowie 18 ungezählte Seiten |
ISSN Quelle: | 1546-170X |
Abstract: | The phase 3 ZUMA-7 trial in second-line large B cell lymphoma demonstrated superiority of anti-CD19 CAR T cell therapy (axicabtagene ciloleucel (axi-cel)) over standard of care (SOC; salvage chemotherapy followed by hematopoietic transplantation) (NCT03391466). Here, we present a prespecified exploratory analysis examining the association between pretreatment tumor characteristics and the efficacy of axi-cel versus SOC. B cell gene expression signature (GES) and CD19 expression associated significantly with improved event-free survival for axi-cel (P = 0.0002 for B cell GES; P = 0.0165 for CD19 expression) but not SOC (P = 0.9374 for B cell GES; P = 0.5526 for CD19 expression). Axi-cel showed superior event-free survival over SOC irrespective of B cell GES and CD19 expression (P = 8.56 × 10-9 for B cell GES high; P = 0.0019 for B cell GES low; P = 3.85 × 10-9 for CD19 gene high; P = 0.0017 for CD19 gene low). Low CD19 expression in malignant cells correlated with a tumor GES consisting of immune-suppressive stromal and myeloid genes, highlighting the inter-relation between malignant cell features and immune contexture substantially impacting axi-cel outcomes. Tumor burden, lactate dehydrogenase and cell-of-origin impacted SOC more than axi-cel outcomes. T cell activation and B cell GES, which are associated with improved axi-cel outcome, decreased with increasing lines of therapy. These data highlight differences in resistance mechanisms to axi-cel and SOC and support earlier intervention with axi-cel. |
DOI: | doi:10.1038/s41591-023-02754-1 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Volltext: https://doi.org/10.1038/s41591-023-02754-1 |
| kostenfrei: Volltext: https://www.nature.com/articles/s41591-023-02754-1 |
| DOI: https://doi.org/10.1038/s41591-023-02754-1 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | B-cell lymphoma |
| Cancer immunotherapy |
| Chemotherapy |
| Predictive markers |
K10plus-PPN: | 1888251433 |
Verknüpfungen: | → Zeitschrift |
Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma / Locke, Frederick [VerfasserIn]; February 2024 (Online-Ressource)