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CD19 CAR T cells are an effective therapy for posttransplant relapse in patients with B-lineage ALL: real-world data from Germany

Patients with precursor B-cell acute lymphoblastic leukemia (pB-ALL) who have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT), have relapsed more than once, or are resistant upfront have a dismal prognosis. CD19-targeted chimeric antigen receptor (CAR) T cells have evol...

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Autores principales: Bader, Peter, Rossig, Claudia, Hutter, Martin, Ayuk, Francis Ayuketang, Baldus, Claudia D., Bücklein, Veit L., Bonig, Halvard, Cario, Gunnar, Einsele, Hermann, Holtick, Udo, Koenecke, Christian, Bakhtiar, Shahrzad, Künkele, Annette, Meisel, Roland, Müller, Fabian, Müller, Ingo, Penack, Olaf, Rettinger, Eva, Sauer, Martin G., Schlegel, Paul-Gerhardt, Soerensen, Jan, von Stackelberg, Arend, Strahm, Brigitte, Hauer, Julia, Feuchtinger, Tobias, Jarisch, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society of Hematology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10242498/
https://www.ncbi.nlm.nih.gov/pubmed/36607834
http://dx.doi.org/10.1182/bloodadvances.2022008981
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author Bader, Peter
Rossig, Claudia
Hutter, Martin
Ayuk, Francis Ayuketang
Baldus, Claudia D.
Bücklein, Veit L.
Bonig, Halvard
Cario, Gunnar
Einsele, Hermann
Holtick, Udo
Koenecke, Christian
Bakhtiar, Shahrzad
Künkele, Annette
Meisel, Roland
Müller, Fabian
Müller, Ingo
Penack, Olaf
Rettinger, Eva
Sauer, Martin G.
Schlegel, Paul-Gerhardt
Soerensen, Jan
von Stackelberg, Arend
Strahm, Brigitte
Hauer, Julia
Feuchtinger, Tobias
Jarisch, Andrea
author_facet Bader, Peter
Rossig, Claudia
Hutter, Martin
Ayuk, Francis Ayuketang
Baldus, Claudia D.
Bücklein, Veit L.
Bonig, Halvard
Cario, Gunnar
Einsele, Hermann
Holtick, Udo
Koenecke, Christian
Bakhtiar, Shahrzad
Künkele, Annette
Meisel, Roland
Müller, Fabian
Müller, Ingo
Penack, Olaf
Rettinger, Eva
Sauer, Martin G.
Schlegel, Paul-Gerhardt
Soerensen, Jan
von Stackelberg, Arend
Strahm, Brigitte
Hauer, Julia
Feuchtinger, Tobias
Jarisch, Andrea
author_sort Bader, Peter
collection PubMed
description Patients with precursor B-cell acute lymphoblastic leukemia (pB-ALL) who have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT), have relapsed more than once, or are resistant upfront have a dismal prognosis. CD19-targeted chimeric antigen receptor (CAR) T cells have evolved as potent immune therapies. Tisagenlecleucel (Tisa-cel) is a commercially available autologous CD19-directed CAR T-cell product. We performed a retrospective study inviting all CAR T-cell centers in Germany to participate. Eighty-one patients with pB-ALL were included. Twenty-eight days after CAR T-cell infusion, 71 patients (87.7%) were in complete response, and 8 (9.9%) were in nonremission. At 2 years, the probabilities of event-free survival (pEFS), relapse-free survival (pRFS), and overall survival (pOS) were 45.3%, 51.7%, and 53.2%, respectively. pEFS was not different in patients without (n = 16, 55.0%) vs with prior allo-HSCT (n = 65, 43.4%). In patients treated after allo-HSCT, the time to relapse after allo-HSCT was a strong predictor of outcome. Patients relapsing within 6 months of allo-HSCT had a disappointing pEFS of 18.4% (pOS = 16.0%); the pEFS for those relapsing later was 55.5% (pOS = 74.8%). Our study provides real-world experience in pediatric, adolescent, and young adult patients with ALL treated with Tisa-cel, where most patients were treated after having relapsed after allo-HSCT. A total of 45.3% were rescued with a single dose of Tisa-cel. Our novel finding that patients with ALL after allo-HSCT had by far a better pEFS if relapse occurred beyond 6 months might be helpful in clinical decision-making and motivates studies to uncover the reasons.
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spelling pubmed-102424982023-06-07 CD19 CAR T cells are an effective therapy for posttransplant relapse in patients with B-lineage ALL: real-world data from Germany Bader, Peter Rossig, Claudia Hutter, Martin Ayuk, Francis Ayuketang Baldus, Claudia D. Bücklein, Veit L. Bonig, Halvard Cario, Gunnar Einsele, Hermann Holtick, Udo Koenecke, Christian Bakhtiar, Shahrzad Künkele, Annette Meisel, Roland Müller, Fabian Müller, Ingo Penack, Olaf Rettinger, Eva Sauer, Martin G. Schlegel, Paul-Gerhardt Soerensen, Jan von Stackelberg, Arend Strahm, Brigitte Hauer, Julia Feuchtinger, Tobias Jarisch, Andrea Blood Adv Clinical Trials and Observations Patients with precursor B-cell acute lymphoblastic leukemia (pB-ALL) who have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT), have relapsed more than once, or are resistant upfront have a dismal prognosis. CD19-targeted chimeric antigen receptor (CAR) T cells have evolved as potent immune therapies. Tisagenlecleucel (Tisa-cel) is a commercially available autologous CD19-directed CAR T-cell product. We performed a retrospective study inviting all CAR T-cell centers in Germany to participate. Eighty-one patients with pB-ALL were included. Twenty-eight days after CAR T-cell infusion, 71 patients (87.7%) were in complete response, and 8 (9.9%) were in nonremission. At 2 years, the probabilities of event-free survival (pEFS), relapse-free survival (pRFS), and overall survival (pOS) were 45.3%, 51.7%, and 53.2%, respectively. pEFS was not different in patients without (n = 16, 55.0%) vs with prior allo-HSCT (n = 65, 43.4%). In patients treated after allo-HSCT, the time to relapse after allo-HSCT was a strong predictor of outcome. Patients relapsing within 6 months of allo-HSCT had a disappointing pEFS of 18.4% (pOS = 16.0%); the pEFS for those relapsing later was 55.5% (pOS = 74.8%). Our study provides real-world experience in pediatric, adolescent, and young adult patients with ALL treated with Tisa-cel, where most patients were treated after having relapsed after allo-HSCT. A total of 45.3% were rescued with a single dose of Tisa-cel. Our novel finding that patients with ALL after allo-HSCT had by far a better pEFS if relapse occurred beyond 6 months might be helpful in clinical decision-making and motivates studies to uncover the reasons. The American Society of Hematology 2023-01-09 /pmc/articles/PMC10242498/ /pubmed/36607834 http://dx.doi.org/10.1182/bloodadvances.2022008981 Text en © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Clinical Trials and Observations
Bader, Peter
Rossig, Claudia
Hutter, Martin
Ayuk, Francis Ayuketang
Baldus, Claudia D.
Bücklein, Veit L.
Bonig, Halvard
Cario, Gunnar
Einsele, Hermann
Holtick, Udo
Koenecke, Christian
Bakhtiar, Shahrzad
Künkele, Annette
Meisel, Roland
Müller, Fabian
Müller, Ingo
Penack, Olaf
Rettinger, Eva
Sauer, Martin G.
Schlegel, Paul-Gerhardt
Soerensen, Jan
von Stackelberg, Arend
Strahm, Brigitte
Hauer, Julia
Feuchtinger, Tobias
Jarisch, Andrea
CD19 CAR T cells are an effective therapy for posttransplant relapse in patients with B-lineage ALL: real-world data from Germany
title CD19 CAR T cells are an effective therapy for posttransplant relapse in patients with B-lineage ALL: real-world data from Germany
title_full CD19 CAR T cells are an effective therapy for posttransplant relapse in patients with B-lineage ALL: real-world data from Germany
title_fullStr CD19 CAR T cells are an effective therapy for posttransplant relapse in patients with B-lineage ALL: real-world data from Germany
title_full_unstemmed CD19 CAR T cells are an effective therapy for posttransplant relapse in patients with B-lineage ALL: real-world data from Germany
title_short CD19 CAR T cells are an effective therapy for posttransplant relapse in patients with B-lineage ALL: real-world data from Germany
title_sort cd19 car t cells are an effective therapy for posttransplant relapse in patients with b-lineage all: real-world data from germany
topic Clinical Trials and Observations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10242498/
https://www.ncbi.nlm.nih.gov/pubmed/36607834
http://dx.doi.org/10.1182/bloodadvances.2022008981
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