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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...

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Autores principales: Wittibschlager, Valerie, Bacher, Ulrike, Seipel, Katja, Porret, Naomi, Wiedemann, Gertrud, Haslebacher, Claudia, Hoffmann, Michèle, Daskalakis, Michael, Akhoundova, Dilara, Pabst, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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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.
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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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