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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...
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/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. |
format | Online Article Text |
id | pubmed-10179014 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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