Copertina

Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma

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 explor...

Descrizione completa

Salvato in:
Dettagli Bibliografici
Autori principali: Locke, Frederick (Autore) , Filosto, Simone (Autore) , Chou, Justin (Autore) , Vardhanabhuti, Saran (Autore) , Perbost, Regis (Autore) , Dreger, Peter (Autore) , Hill, Brian T. (Autore) , Lee, Catherine (Autore) , Zinzani, Pier L. (Autore) , Kröger, Nicolaus (Autore) , López-Guillermo, Armando (Autore) , Greinix, Hildegard (Autore) , Zhang, Wangshu (Autore) , Tiwari, Gayatri (Autore) , Budka, Justin (Autore) , Marincola, Francesco M. (Autore) , To, Christina (Autore) , Mattie, Mike (Autore) , Schupp, Marco (Autore) , Cheng, Paul (Autore) , Bot, Adrian (Autore) , Shen, Rhine (Autore) , Bedognetti, Davide (Autore) , Miao, Harry (Autore) , Galon, Jérôme (Autore)
Natura: Article (Journal)
Lingua:inglese
Pubblicazione: February 2024
In: Nature medicine
Year: 2024, Volume: 30, Fascicolo: 2, Pages: 507-518
ISSN:1546-170X
DOI:10.1038/s41591-023-02754-1
Accesso online:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41591-023-02754-1
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41591-023-02754-1
Testo
Note sull'autore: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
Descrizione
Riassunto: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.
Descrizione del documento:Online veröffentlicht: 17. Januar 2024
Gesehen am 10.05.2024
Descrizione fisica:Online Resource
ISSN:1546-170X
DOI:10.1038/s41591-023-02754-1

Documenti analoghi