Format:
29
ISSN:
1546-170X
Content:
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.
Note:
Online veröffentlicht: 17. Januar 2024
,
Gesehen am 10.05.2024
In:
Nature medicine, [New York, NY] : Springer Nature, 1995, 30(2024), Heft 2, S. 507-518, 11 gezählte sowie 18 ungezählte Seiten, 1546-170X
In:
volume:30
In:
year:2024
In:
number:2
In:
month:02
In:
pages:507-518
In:
extent:29
Language:
English
DOI:
10.1038/s41591-023-02754-1
URL:
Volltext
(kostenfrei)
URL:
Volltext
(kostenfrei)
