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CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope

Patients with non-Hodgkin lymphomas (NHLs) resistant to standard therapies have a dismal prognosis. The outcome is even poorer in patients relapsing after autologous stem cell transplantation. Most of these patients do not qualify for an allogeneic hematopoietic cell transplantation (HCT) due to ref...

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Detalles Bibliográficos
Autores principales: Hopfinger, Georg, Jäger, Ulrich, Worel, Nina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746029/
https://www.ncbi.nlm.nih.gov/pubmed/31723824
http://dx.doi.org/10.1097/HS9.0000000000000185
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author Hopfinger, Georg
Jäger, Ulrich
Worel, Nina
author_facet Hopfinger, Georg
Jäger, Ulrich
Worel, Nina
author_sort Hopfinger, Georg
collection PubMed
description Patients with non-Hodgkin lymphomas (NHLs) resistant to standard therapies have a dismal prognosis. The outcome is even poorer in patients relapsing after autologous stem cell transplantation. Most of these patients do not qualify for an allogeneic hematopoietic cell transplantation (HCT) due to refractory disease, lack of a suitable allogeneic donor, higher age, or cumulative toxicity of previous chemotherapy. Despite patients undergoing allogeneic HCT normally profit from a graft-versus-lymphoma effect, overall survival in patients with NHL after HCT remains short. Therefore, novel treatment modalities are urgently needed. Chimeric antigen receptor (CAR)-T cells, a new class of cellular immunotherapy involving ex vivo genetic modification of T cells to incorporate an engineered CAR have been used in clinical trials. In the majority of studies, B cell malignancies treated with CD19 targeting CAR-T cells have been analyzed. Recently, results from 2 CD19 directed CAR-T cell trials with an increased follow-up of patients led to Food and Drug Administration and European Medicines Agency approval of tisagenlecleucel and axicabtagene ciloleucel. Common adverse events (AEs) include cytokine release syndrome and neurological toxicity, which may require admission to an intensive care unit, B cell aplasia and hemophagocytic lymphohistiocytosis. These AEs are manageable when treated by an appropriately trained team following established algorithm. In this review, we summarize the results of 3 large phase II CD19 CAR-T cell trials and focus on AEs. We also provide a perspective of ongoing activity in this field with the intend to improve the potency of this emerging novel therapy.
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spelling pubmed-67460292019-11-13 CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope Hopfinger, Georg Jäger, Ulrich Worel, Nina Hemasphere Review Article Patients with non-Hodgkin lymphomas (NHLs) resistant to standard therapies have a dismal prognosis. The outcome is even poorer in patients relapsing after autologous stem cell transplantation. Most of these patients do not qualify for an allogeneic hematopoietic cell transplantation (HCT) due to refractory disease, lack of a suitable allogeneic donor, higher age, or cumulative toxicity of previous chemotherapy. Despite patients undergoing allogeneic HCT normally profit from a graft-versus-lymphoma effect, overall survival in patients with NHL after HCT remains short. Therefore, novel treatment modalities are urgently needed. Chimeric antigen receptor (CAR)-T cells, a new class of cellular immunotherapy involving ex vivo genetic modification of T cells to incorporate an engineered CAR have been used in clinical trials. In the majority of studies, B cell malignancies treated with CD19 targeting CAR-T cells have been analyzed. Recently, results from 2 CD19 directed CAR-T cell trials with an increased follow-up of patients led to Food and Drug Administration and European Medicines Agency approval of tisagenlecleucel and axicabtagene ciloleucel. Common adverse events (AEs) include cytokine release syndrome and neurological toxicity, which may require admission to an intensive care unit, B cell aplasia and hemophagocytic lymphohistiocytosis. These AEs are manageable when treated by an appropriately trained team following established algorithm. In this review, we summarize the results of 3 large phase II CD19 CAR-T cell trials and focus on AEs. We also provide a perspective of ongoing activity in this field with the intend to improve the potency of this emerging novel therapy. Wolters Kluwer Health 2019-03-08 /pmc/articles/PMC6746029/ /pubmed/31723824 http://dx.doi.org/10.1097/HS9.0000000000000185 Text en Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association. http://creativecommons.org/licenses/by-nc-nd/4.0 This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0
spellingShingle Review Article
Hopfinger, Georg
Jäger, Ulrich
Worel, Nina
CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope
title CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope
title_full CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope
title_fullStr CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope
title_full_unstemmed CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope
title_short CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope
title_sort car-t cell therapy in diffuse large b cell lymphoma: hype and hope
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746029/
https://www.ncbi.nlm.nih.gov/pubmed/31723824
http://dx.doi.org/10.1097/HS9.0000000000000185
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