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Thrombotic Events Are Unusual Toxicities of Chimeric Antigen Receptor T-Cell Therapies

Chimeric antigen receptor (CAR) T-cell therapy has greatly transformed the treatment and prognosis of B-cell hematological malignancies. As CAR T-cell therapy continues to be more readily adopted and indications increase, the field’s recognition of emerging toxicities will continue to grow. Among th...

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Autores principales: Schorr, Christopher, Forindez, Jorge, Espinoza-Gutarra, Manuel, Mehta, Rakesh, Grover, Natalie, Perna, Fabiana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10179014/
https://www.ncbi.nlm.nih.gov/pubmed/37176053
http://dx.doi.org/10.3390/ijms24098349
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author Schorr, Christopher
Forindez, Jorge
Espinoza-Gutarra, Manuel
Mehta, Rakesh
Grover, Natalie
Perna, Fabiana
author_facet Schorr, Christopher
Forindez, Jorge
Espinoza-Gutarra, Manuel
Mehta, Rakesh
Grover, Natalie
Perna, Fabiana
author_sort Schorr, Christopher
collection PubMed
description Chimeric antigen receptor (CAR) T-cell therapy has greatly transformed the treatment and prognosis of B-cell hematological malignancies. As CAR T-cell therapy continues to be more readily adopted and indications increase, the field’s recognition of emerging toxicities will continue to grow. Among the adverse events associated with CAR T-cell therapy, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are the most common toxicities, while thrombotic events represent an under-reported, life-endangering complication. To determine thrombosis incidence post CAR T-cell therapy, we performed a multi-center, retrospective study on CAR T-cell therapy adult patients (N = 140) from Indiana University Simon Cancer Center and the University of North Carolina Medical Center treated from 2017 to 2022 for relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL, N = 3), diffuse large B-cell lymphoma (DLBCL, N = 92), follicular lymphoma (FL, N = 9), mantle cell lymphoma (MCL, N = 2), and multiple myeloma (MM, N = 34). We report 10 (7.14%) thrombotic events related to CAR T-cell therapy (DLBCL: N = 8, FL: N = 1, MM: N = 1) including 9 primary venous events and 1 arterial event that occurred with median time of 23.5 days post CAR T-cell infusion. In search of parameters associated with such events, we performed multivariate analyses of coagulation parameters (i.e., PT, PTT, and D-Dimer), scoring for adverse events (Padua Score and ISTH DIC Score) and grading for CAR T-cell toxicity severity (CRS grade and ICANS grade) and found that D-Dimer peak elevation and ICANS grade were significantly associated with post-CAR T-cell infusion thrombosis. While the pathophysiology of CAR T-cell associated coagulopathy remains unknown, our study serves to develop awareness of these emerging and unusual complications.
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spelling pubmed-101790142023-05-13 Thrombotic Events Are Unusual Toxicities of Chimeric Antigen Receptor T-Cell Therapies Schorr, Christopher Forindez, Jorge Espinoza-Gutarra, Manuel Mehta, Rakesh Grover, Natalie Perna, Fabiana Int J Mol Sci Communication Chimeric antigen receptor (CAR) T-cell therapy has greatly transformed the treatment and prognosis of B-cell hematological malignancies. As CAR T-cell therapy continues to be more readily adopted and indications increase, the field’s recognition of emerging toxicities will continue to grow. Among the adverse events associated with CAR T-cell therapy, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are the most common toxicities, while thrombotic events represent an under-reported, life-endangering complication. To determine thrombosis incidence post CAR T-cell therapy, we performed a multi-center, retrospective study on CAR T-cell therapy adult patients (N = 140) from Indiana University Simon Cancer Center and the University of North Carolina Medical Center treated from 2017 to 2022 for relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL, N = 3), diffuse large B-cell lymphoma (DLBCL, N = 92), follicular lymphoma (FL, N = 9), mantle cell lymphoma (MCL, N = 2), and multiple myeloma (MM, N = 34). We report 10 (7.14%) thrombotic events related to CAR T-cell therapy (DLBCL: N = 8, FL: N = 1, MM: N = 1) including 9 primary venous events and 1 arterial event that occurred with median time of 23.5 days post CAR T-cell infusion. In search of parameters associated with such events, we performed multivariate analyses of coagulation parameters (i.e., PT, PTT, and D-Dimer), scoring for adverse events (Padua Score and ISTH DIC Score) and grading for CAR T-cell toxicity severity (CRS grade and ICANS grade) and found that D-Dimer peak elevation and ICANS grade were significantly associated with post-CAR T-cell infusion thrombosis. While the pathophysiology of CAR T-cell associated coagulopathy remains unknown, our study serves to develop awareness of these emerging and unusual complications. MDPI 2023-05-06 /pmc/articles/PMC10179014/ /pubmed/37176053 http://dx.doi.org/10.3390/ijms24098349 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 Communication
Schorr, Christopher
Forindez, Jorge
Espinoza-Gutarra, Manuel
Mehta, Rakesh
Grover, Natalie
Perna, Fabiana
Thrombotic Events Are Unusual Toxicities of Chimeric Antigen Receptor T-Cell Therapies
title Thrombotic Events Are Unusual Toxicities of Chimeric Antigen Receptor T-Cell Therapies
title_full Thrombotic Events Are Unusual Toxicities of Chimeric Antigen Receptor T-Cell Therapies
title_fullStr Thrombotic Events Are Unusual Toxicities of Chimeric Antigen Receptor T-Cell Therapies
title_full_unstemmed Thrombotic Events Are Unusual Toxicities of Chimeric Antigen Receptor T-Cell Therapies
title_short Thrombotic Events Are Unusual Toxicities of Chimeric Antigen Receptor T-Cell Therapies
title_sort thrombotic events are unusual toxicities of chimeric antigen receptor t-cell therapies
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10179014/
https://www.ncbi.nlm.nih.gov/pubmed/37176053
http://dx.doi.org/10.3390/ijms24098349
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