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

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Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma. / Locke, Frederick L; Filosto, Simone; Chou, Justin; Vardhanabhuti, Saran; Perbost, Regis; Dreger, Peter; Hill, Brian T; Lee, Catherine; Zinzani, Pier L; Kröger, Nicolaus; López-Guillermo, Armando; Greinix, Hildegard; Zhang, Wangshu; Tiwari, Gayatri; Budka, Justin; Marincola, Francesco M; To, Christina; Mattie, Mike; Schupp, Marco; Cheng, Paul; Bot, Adrian; Shen, Rhine; Bedognetti, Davide; Miao, Harry; Galon, Jérôme.

in: NAT MED, Jahrgang 30, Nr. 2, 02.2024, S. 507-518.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Locke, FL, Filosto, S, Chou, J, Vardhanabhuti, S, Perbost, R, Dreger, P, Hill, BT, Lee, C, Zinzani, PL, Kröger, N, López-Guillermo, A, Greinix, H, Zhang, W, Tiwari, G, Budka, J, Marincola, FM, To, C, Mattie, M, Schupp, M, Cheng, P, Bot, A, Shen, R, Bedognetti, D, Miao, H & Galon, J 2024, 'Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma', NAT MED, Jg. 30, Nr. 2, S. 507-518. https://doi.org/10.1038/s41591-023-02754-1

APA

Locke, F. L., Filosto, S., Chou, J., Vardhanabhuti, S., Perbost, R., Dreger, P., Hill, B. T., Lee, C., Zinzani, P. L., Kröger, N., López-Guillermo, A., Greinix, H., Zhang, W., Tiwari, G., Budka, J., Marincola, F. M., To, C., Mattie, M., Schupp, M., ... Galon, J. (2024). Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma. NAT MED, 30(2), 507-518. https://doi.org/10.1038/s41591-023-02754-1

Vancouver

Locke FL, Filosto S, Chou J, Vardhanabhuti S, Perbost R, Dreger P et al. Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma. NAT MED. 2024 Feb;30(2):507-518. https://doi.org/10.1038/s41591-023-02754-1

Bibtex

@article{75c4553601424f1691fc4225a0e9e642,
title = "Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma",
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.",
author = "Locke, {Frederick L} and Simone Filosto and Justin Chou and Saran Vardhanabhuti and Regis Perbost and Peter Dreger and Hill, {Brian T} and Catherine Lee and Zinzani, {Pier L} and Nicolaus Kr{\"o}ger and Armando L{\'o}pez-Guillermo and Hildegard Greinix and Wangshu Zhang and Gayatri Tiwari and Justin Budka and Marincola, {Francesco M} and Christina To and Mike Mattie and Marco Schupp and Paul Cheng and Adrian Bot and Rhine Shen and Davide Bedognetti and Harry Miao and J{\'e}r{\^o}me Galon",
note = "{\textcopyright} 2024. The Author(s).",
year = "2024",
month = feb,
doi = "10.1038/s41591-023-02754-1",
language = "English",
volume = "30",
pages = "507--518",
journal = "NAT MED",
issn = "1078-8956",
publisher = "NATURE PUBLISHING GROUP",
number = "2",

}

RIS

TY - JOUR

T1 - Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma

AU - Locke, Frederick L

AU - Filosto, Simone

AU - Chou, Justin

AU - Vardhanabhuti, Saran

AU - Perbost, Regis

AU - Dreger, Peter

AU - Hill, Brian T

AU - Lee, Catherine

AU - Zinzani, Pier L

AU - Kröger, Nicolaus

AU - López-Guillermo, Armando

AU - Greinix, Hildegard

AU - Zhang, Wangshu

AU - Tiwari, Gayatri

AU - Budka, Justin

AU - Marincola, Francesco M

AU - To, Christina

AU - Mattie, Mike

AU - Schupp, Marco

AU - Cheng, Paul

AU - Bot, Adrian

AU - Shen, Rhine

AU - Bedognetti, Davide

AU - Miao, Harry

AU - Galon, Jérôme

N1 - © 2024. The Author(s).

PY - 2024/2

Y1 - 2024/2

N2 - 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.

AB - 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.

U2 - 10.1038/s41591-023-02754-1

DO - 10.1038/s41591-023-02754-1

M3 - SCORING: Journal article

C2 - 38233586

VL - 30

SP - 507

EP - 518

JO - NAT MED

JF - NAT MED

SN - 1078-8956

IS - 2

ER -