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CAR T-Cell Persistence Correlates with Improved Outcome in Patients with B-Cell Lymphoma
Chimeric antigen receptor (CAR) T-cell therapy has led to profound and durable tumor responses in a relevant subset of patients with relapsed/refractory (r/r) B-cell lymphomas. Still, some patients show insufficient benefit or relapse after CAR T-cell therapy. We performed a retrospective study to i...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10056741/ https://www.ncbi.nlm.nih.gov/pubmed/36982764 http://dx.doi.org/10.3390/ijms24065688 |
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author | Wittibschlager, Valerie Bacher, Ulrike Seipel, Katja Porret, Naomi Wiedemann, Gertrud Haslebacher, Claudia Hoffmann, Michèle Daskalakis, Michael Akhoundova, Dilara Pabst, Thomas |
author_facet | Wittibschlager, Valerie Bacher, Ulrike Seipel, Katja Porret, Naomi Wiedemann, Gertrud Haslebacher, Claudia Hoffmann, Michèle Daskalakis, Michael Akhoundova, Dilara Pabst, Thomas |
author_sort | Wittibschlager, Valerie |
collection | PubMed |
description | Chimeric antigen receptor (CAR) T-cell therapy has led to profound and durable tumor responses in a relevant subset of patients with relapsed/refractory (r/r) B-cell lymphomas. Still, some patients show insufficient benefit or relapse after CAR T-cell therapy. We performed a retrospective study to investigate the correlation between CAR T-cell persistence in the peripheral blood (PB) at 6 months, assessed by droplet digital PCR (ddPCR), with CAR T-cell treatment outcome. 92 patients with r/r B-cell lymphomas were treated with CD19-targeting CAR T-cell therapies at our institution between 01/2019–08/2022. Six months post-treatment, 15 (16%) patients had no detectable circulating CAR-T constructs by ddPCR. Patients with CAR T-cell persistence had a significantly higher CAR T-cell peak (5432 vs. 620 copies/ug cfDNA, p = 0.0096), as well as higher incidence of immune effector cell-associated neurotoxicity syndrome (37% vs. 7%, p = 0.0182). After a median follow-up of 8.5 months, 31 (34%) patients relapsed. Lymphoma relapses were less frequent among patients with CAR T-cell persistence (29% vs. 60%, p = 0.0336), and CAR T-cell persistence in the PB at 6 months was associated with longer progression-free survival (PFS) (HR 2.79, 95% CI: 1.09–7.11, p = 0.0319). Moreover, we observed a trend towards improved overall survival (OS) (HR 1.99, 95% CI: 0.68–5.82, p = 0.2092) for these patients. In our cohort of 92 B-cell lymphomas, CAR T-cell persistence at 6 months was associated with lower relapse rates and longer PFS. Moreover, our data confirm that 4-1BB-CAR T-cells have a longer persistence as compared to CD-28-based CAR T-cells. |
format | Online Article Text |
id | pubmed-10056741 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100567412023-03-30 CAR T-Cell Persistence Correlates with Improved Outcome in Patients with B-Cell Lymphoma Wittibschlager, Valerie Bacher, Ulrike Seipel, Katja Porret, Naomi Wiedemann, Gertrud Haslebacher, Claudia Hoffmann, Michèle Daskalakis, Michael Akhoundova, Dilara Pabst, Thomas Int J Mol Sci Article Chimeric antigen receptor (CAR) T-cell therapy has led to profound and durable tumor responses in a relevant subset of patients with relapsed/refractory (r/r) B-cell lymphomas. Still, some patients show insufficient benefit or relapse after CAR T-cell therapy. We performed a retrospective study to investigate the correlation between CAR T-cell persistence in the peripheral blood (PB) at 6 months, assessed by droplet digital PCR (ddPCR), with CAR T-cell treatment outcome. 92 patients with r/r B-cell lymphomas were treated with CD19-targeting CAR T-cell therapies at our institution between 01/2019–08/2022. Six months post-treatment, 15 (16%) patients had no detectable circulating CAR-T constructs by ddPCR. Patients with CAR T-cell persistence had a significantly higher CAR T-cell peak (5432 vs. 620 copies/ug cfDNA, p = 0.0096), as well as higher incidence of immune effector cell-associated neurotoxicity syndrome (37% vs. 7%, p = 0.0182). After a median follow-up of 8.5 months, 31 (34%) patients relapsed. Lymphoma relapses were less frequent among patients with CAR T-cell persistence (29% vs. 60%, p = 0.0336), and CAR T-cell persistence in the PB at 6 months was associated with longer progression-free survival (PFS) (HR 2.79, 95% CI: 1.09–7.11, p = 0.0319). Moreover, we observed a trend towards improved overall survival (OS) (HR 1.99, 95% CI: 0.68–5.82, p = 0.2092) for these patients. In our cohort of 92 B-cell lymphomas, CAR T-cell persistence at 6 months was associated with lower relapse rates and longer PFS. Moreover, our data confirm that 4-1BB-CAR T-cells have a longer persistence as compared to CD-28-based CAR T-cells. MDPI 2023-03-16 /pmc/articles/PMC10056741/ /pubmed/36982764 http://dx.doi.org/10.3390/ijms24065688 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wittibschlager, Valerie Bacher, Ulrike Seipel, Katja Porret, Naomi Wiedemann, Gertrud Haslebacher, Claudia Hoffmann, Michèle Daskalakis, Michael Akhoundova, Dilara Pabst, Thomas CAR T-Cell Persistence Correlates with Improved Outcome in Patients with B-Cell Lymphoma |
title | CAR T-Cell Persistence Correlates with Improved Outcome in Patients with B-Cell Lymphoma |
title_full | CAR T-Cell Persistence Correlates with Improved Outcome in Patients with B-Cell Lymphoma |
title_fullStr | CAR T-Cell Persistence Correlates with Improved Outcome in Patients with B-Cell Lymphoma |
title_full_unstemmed | CAR T-Cell Persistence Correlates with Improved Outcome in Patients with B-Cell Lymphoma |
title_short | CAR T-Cell Persistence Correlates with Improved Outcome in Patients with B-Cell Lymphoma |
title_sort | car t-cell persistence correlates with improved outcome in patients with b-cell lymphoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10056741/ https://www.ncbi.nlm.nih.gov/pubmed/36982764 http://dx.doi.org/10.3390/ijms24065688 |
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