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...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
February 2024
|
| In: |
Nature medicine
Year: 2024, Jahrgang: 30, Heft: 2, Pages: 507-518 |
| ISSN: | 1546-170X |
| DOI: | 10.1038/s41591-023-02754-1 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41591-023-02754-1 Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41591-023-02754-1 
|
| Verfasserangaben: | 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 |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1888251433 | ||
| 003 | DE-627 | ||
| 005 | 20250116230752.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240510s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41591-023-02754-1 |2 doi | |
| 035 | |a (DE-627)1888251433 | ||
| 035 | |a (DE-599)KXP1888251433 | ||
| 035 | |a (OCoLC)1443675858 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Locke, Frederick |e VerfasserIn |0 (DE-588)1328903168 |0 (DE-627)1888251883 |4 aut | |
| 245 | 1 | 0 | |a Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma |c 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 |
| 264 | 1 | |c February 2024 | |
| 300 | |a 29 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Online veröffentlicht: 17. Januar 2024 | ||
| 500 | |a Gesehen am 10.05.2024 | ||
| 520 | |a 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. | ||
| 650 | 4 | |a B-cell lymphoma | |
| 650 | 4 | |a Cancer immunotherapy | |
| 650 | 4 | |a Chemotherapy | |
| 650 | 4 | |a Predictive markers | |
| 700 | 1 | |a Filosto, Simone |e VerfasserIn |4 aut | |
| 700 | 1 | |a Chou, Justin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Vardhanabhuti, Saran |e VerfasserIn |4 aut | |
| 700 | 1 | |a Perbost, Regis |e VerfasserIn |4 aut | |
| 700 | 1 | |a Dreger, Peter |e VerfasserIn |0 (DE-588)1028891881 |0 (DE-627)732699894 |0 (DE-576)376320966 |4 aut | |
| 700 | 1 | |a Hill, Brian T. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lee, Catherine |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zinzani, Pier L. |e VerfasserIn |4 aut | |
| 700 | 1 | |8 1\p |a Kröger, Nicolaus |d 1959- |e VerfasserIn |0 (DE-588)112156533 |0 (DE-627)477107354 |0 (DE-576)167115103 |4 aut | |
| 700 | 1 | |a López-Guillermo, Armando |e VerfasserIn |4 aut | |
| 700 | 1 | |a Greinix, Hildegard |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zhang, Wangshu |e VerfasserIn |4 aut | |
| 700 | 1 | |a Tiwari, Gayatri |e VerfasserIn |4 aut | |
| 700 | 1 | |a Budka, Justin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Marincola, Francesco M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a To, Christina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mattie, Mike |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schupp, Marco |e VerfasserIn |4 aut | |
| 700 | 1 | |a Cheng, Paul |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bot, Adrian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Shen, Rhine |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bedognetti, Davide |e VerfasserIn |4 aut | |
| 700 | 1 | |a Miao, Harry |e VerfasserIn |4 aut | |
| 700 | 1 | |a Galon, Jérôme |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature medicine |d [New York, NY] : Springer Nature, 1995 |g 30(2024), Heft 2, S. 507-518, 11 gezählte sowie 18 ungezählte Seiten |h Online-Ressource |w (DE-627)301511640 |w (DE-600)1484517-9 |w (DE-576)288571274 |x 1546-170X |7 nnas |a Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma |
| 773 | 1 | 8 | |g volume:30 |g year:2024 |g number:2 |g month:02 |g pages:507-518 |g extent:29 |a Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41591-023-02754-1 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://www.nature.com/articles/s41591-023-02754-1 |x Verlag |z kostenfrei |3 Volltext |
| 883 | |8 1\p |a cgwrk |d 20241001 |q DE-101 |u https://d-nb.info/provenance/plan#cgwrk | ||
| 951 | |a AR | ||
| 992 | |a 20240510 | ||
| 993 | |a Article | ||
| 994 | |a 2024 | ||
| 998 | |g 1028891881 |a Dreger, Peter |m 1028891881:Dreger, Peter |d 910000 |d 910100 |e 910000PD1028891881 |e 910100PD1028891881 |k 0/910000/ |k 1/910000/910100/ |p 6 | ||
| 999 | |a KXP-PPN1888251433 |e 4521998445 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"name":{"displayForm":["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"]},"recId":"1888251433","note":["Online veröffentlicht: 17. Januar 2024","Gesehen am 10.05.2024"],"origin":[{"dateIssuedDisp":"February 2024","dateIssuedKey":"2024"}],"id":{"eki":["1888251433"],"doi":["10.1038/s41591-023-02754-1"]},"language":["eng"],"type":{"media":"Online-Ressource","bibl":"article-journal"},"person":[{"role":"aut","display":"Locke, Frederick","family":"Locke","given":"Frederick"},{"role":"aut","given":"Simone","family":"Filosto","display":"Filosto, Simone"},{"role":"aut","given":"Justin","family":"Chou","display":"Chou, Justin"},{"given":"Saran","family":"Vardhanabhuti","display":"Vardhanabhuti, Saran","role":"aut"},{"display":"Perbost, Regis","family":"Perbost","given":"Regis","role":"aut"},{"family":"Dreger","display":"Dreger, Peter","given":"Peter","role":"aut"},{"role":"aut","family":"Hill","display":"Hill, Brian T.","given":"Brian T."},{"given":"Catherine","family":"Lee","display":"Lee, Catherine","role":"aut"},{"role":"aut","family":"Zinzani","display":"Zinzani, Pier L.","given":"Pier L."},{"given":"Nicolaus","display":"Kröger, Nicolaus","family":"Kröger","role":"aut"},{"given":"Armando","display":"López-Guillermo, Armando","family":"López-Guillermo","role":"aut"},{"display":"Greinix, Hildegard","family":"Greinix","given":"Hildegard","role":"aut"},{"role":"aut","display":"Zhang, Wangshu","family":"Zhang","given":"Wangshu"},{"role":"aut","given":"Gayatri","family":"Tiwari","display":"Tiwari, Gayatri"},{"role":"aut","display":"Budka, Justin","family":"Budka","given":"Justin"},{"role":"aut","given":"Francesco M.","display":"Marincola, Francesco M.","family":"Marincola"},{"role":"aut","given":"Christina","family":"To","display":"To, Christina"},{"family":"Mattie","display":"Mattie, Mike","given":"Mike","role":"aut"},{"display":"Schupp, Marco","family":"Schupp","given":"Marco","role":"aut"},{"role":"aut","display":"Cheng, Paul","family":"Cheng","given":"Paul"},{"role":"aut","display":"Bot, Adrian","family":"Bot","given":"Adrian"},{"role":"aut","given":"Rhine","family":"Shen","display":"Shen, Rhine"},{"role":"aut","family":"Bedognetti","display":"Bedognetti, Davide","given":"Davide"},{"family":"Miao","display":"Miao, Harry","given":"Harry","role":"aut"},{"role":"aut","given":"Jérôme","display":"Galon, Jérôme","family":"Galon"}],"title":[{"title":"Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma","title_sort":"Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma"}],"physDesc":[{"extent":"29 S."}],"relHost":[{"title":[{"title_sort":"Nature medicine","title":"Nature medicine"}],"physDesc":[{"extent":"Online-Ressource"}],"part":{"year":"2024","extent":"29","issue":"2","volume":"30","pages":"507-518","text":"30(2024), Heft 2, S. 507-518, 11 gezählte sowie 18 ungezählte Seiten"},"origin":[{"publisherPlace":"[New York, NY] ; New York, NY","dateIssuedDisp":"2017-","dateIssuedKey":"2017","publisher":"Springer Nature ; Nature America Inc."}],"language":["eng"],"id":{"eki":["301511640"],"issn":["1546-170X"],"zdb":["1484517-9"]},"type":{"media":"Online-Ressource","bibl":"periodical"},"pubHistory":["1.1995 -"],"recId":"301511640","note":["Gesehen am 24. Juli 2018"],"disp":"Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphomaNature medicine"}]} | ||
| SRT | |a LOCKEFREDEIMPACTOFTU2024 | ||