Vollständiger Abstract
Worum geht es in dieser Arbeit?
Abstract It remains uncertain whether lower CD19 expression is clinically relevant for outcomes of CD19 CAR-T therapy of large B-cell lymphoma (LBCL). We conducted an integrative analysis of tumor CD19 levels with centralized quantitative assessment by flow cytometry (FC), immunohistochemistry and RNA-sequencing in a LBCL cohort (n=301). Pre-treatment CD19 by FC correlated with 1-year progression-free survival following axicabtagene ciloleucel or lisocabtagene maraleucel (16%, 53% and 64% for CD19low, CD19intermediate and CD19high, respectively; p=0.005). After CAR-T relapse, proportion of CD19low tumors increased (from 17% to 35%). Concordant associations were observed by immunohistochemistry and RNA-sequencing. Transcriptomic profiling linked lower CD19 to inflammatory pathways, validated in an external LBCL cohort (n=1,017). Genetic loss of the CD19 locus was observed in 8% of pre-CAR-T and 11% of post-CAR-T tumors (p=0.82), while no CD19 coding mutations were identified. Overall, CD19 expression is a clinically meaningful determinant of CAR-T outcomes, supporting quantitative assessment to improve risk stratification.
Bibliografischer Nachweis
Publikationsdaten
- Autor:innen
- Magdalena Corona, Aaron Gillmor, Kimon V. Argyropoulos, Teng Fei, Maria Isabel Sotelo-Alva, Mohammad Alhomoud, Parastoo B. Dahi, Anthony F. Daniyan, Mark T.A. Donoghue, Sigrun Einarsdottir, Lorenzo Falchi, Qi Gao, Gregory Goldgof, Marina Gomez-Llobell, Erel Joffe, Richard J. Lin, Alejandro Luna de Abia, Efrat Luttwak, M. Lia. Palomba, Jae H. Park, Sandeep S. Raj, Kai Rejeski, Alfredo Rivas-Delgado, Gilles Salles, Jaime Sanz, Michael Scordo, Gunjan L. Shah, Sulov Chalise, Manik Uppal, Anna Gurevich-Shapiro, Menglei Zhu, Miguel-Angel Perales, Allison L. Richards, Mikhail Roshal, Roni Shouval
- Quelle
- Blood Cancer Discovery
- Publikation
- 2026-01-01
- Band / Ausgabe
- Nicht angegeben
- Seiten
- Nicht angegeben
- ISSN / ISBN
- 2643-3230, 2643-3249
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Zitierfähiger Nachweis
Magdalena Corona, Aaron Gillmor, Kimon V. Argyropoulos, Teng Fei, Maria Isabel Sotelo-Alva, Mohammad Alhomoud, Parastoo B. Dahi, Anthony F. Daniyan, Mark T.A. Donoghue, Sigrun Einarsdottir, Lorenzo Falchi, Qi Gao, Gregory Goldgof, Marina Gomez-Llobell, Erel Joffe, Richard J. Lin, Alejandro Luna de Abia, Efrat Luttwak, M. Lia. Palomba, Jae H. Park, Sandeep S. Raj, Kai Rejeski, Alfredo Rivas-Delgado, Gilles Salles, Jaime Sanz, Michael Scordo, Gunjan L. Shah, Sulov Chalise, Manik Uppal, Anna Gurevich-Shapiro, Menglei Zhu, Miguel-Angel Perales, Allison L. Richards, Mikhail Roshal, Roni Shouval (2026). Tumor CD19 Expression Determines Distinct Clinical Outcomes After CD19 CAR T-Cell Therapy in Large B-Cell Lymphoma. Blood Cancer Discovery. https://doi.org/10.1158/2643-3230.bcd-25-0501