Cargando…

Novel Use of Extracorporeal Blood Purification for Treatment of Severe, Refractory Neurotoxicity After Chimeric Antigen Receptor T-Cell Therapy—A Case Report

BACKGROUND: Chimeric antigen receptor T-cell therapies (CAR-T) are transforming the treatment of B-cell leukemias and lymphomas. Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome represent common, potentially life-threatening toxicities from chimeric antigen recept...

Descripción completa

Detalles Bibliográficos
Autores principales: Singbartl, Kai, Rosenthal, Allison, Leis, Jose, Patel, Bhavesh, Sen, Ayan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245117/
https://www.ncbi.nlm.nih.gov/pubmed/34235458
http://dx.doi.org/10.1097/CCE.0000000000000472
_version_ 1783716057732612096
author Singbartl, Kai
Rosenthal, Allison
Leis, Jose
Patel, Bhavesh
Sen, Ayan
author_facet Singbartl, Kai
Rosenthal, Allison
Leis, Jose
Patel, Bhavesh
Sen, Ayan
author_sort Singbartl, Kai
collection PubMed
description BACKGROUND: Chimeric antigen receptor T-cell therapies (CAR-T) are transforming the treatment of B-cell leukemias and lymphomas. Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome represent common, potentially life-threatening toxicities from chimeric antigen receptor T-cell therapy treatment. CASE SUMMARY: We present a 53-year-old patient with primary refractory high-grade B-cell lymphoma who developed severe, refractory neurotoxicity following chimeric antigen receptor T-cell therapy but exhibited complete recovery after extracorporeal blood purification with CytoSorb (CytoSorbents, Monmouth Junction, NJ). Six days after chimeric antigen receptor T-cell therapy infusion, the patient developed cytokine release syndrome grade 3, prompting administration of dexamethasone and tocilizumab, a monoclonal antibody against the interleukin-6 receptor. His C-reactive protein levels started to decrease with tocilizumab and dexamethasone treatments. However, his ferritin levels continued to rise, and his interleukin-6 levels were above the upper detection threshold. Thirty-six hours later, the patient showed improved cytokine release syndrome but developed severe immune effector cell-associated neurotoxicity syndrome with predominant encephalopathy (grade 3) despite treatment with dexamethasone/methylprednisolone, tocilizumab, and anakinra. We therefore sought a rescue strategy to remove inflammatory mediators. Following emergency use authorization, we initiated extracorporeal blood purification with CytoSorb (CytoSorbents). Four-day extracorporeal blood purification resulted in complete resolution of immune effector cell-associated neurotoxicity syndrome and greater than 95% reduction in interleukin-6 levels without side effects. The patient was discharged home 10 days later with no signs of neurotoxicity or other secondary end-organ dysfunction. CONCLUSIONS: Our case represents the first reported, successful application of extracorporeal blood purification with CytoSorb (CytoSorbents) to treat severe, refractory neurotoxicity following chimeric antigen receptor T-cell therapy.
format Online
Article
Text
id pubmed-8245117
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Lippincott Williams & Wilkins
record_format MEDLINE/PubMed
spelling pubmed-82451172021-07-06 Novel Use of Extracorporeal Blood Purification for Treatment of Severe, Refractory Neurotoxicity After Chimeric Antigen Receptor T-Cell Therapy—A Case Report Singbartl, Kai Rosenthal, Allison Leis, Jose Patel, Bhavesh Sen, Ayan Crit Care Explor Case Report BACKGROUND: Chimeric antigen receptor T-cell therapies (CAR-T) are transforming the treatment of B-cell leukemias and lymphomas. Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome represent common, potentially life-threatening toxicities from chimeric antigen receptor T-cell therapy treatment. CASE SUMMARY: We present a 53-year-old patient with primary refractory high-grade B-cell lymphoma who developed severe, refractory neurotoxicity following chimeric antigen receptor T-cell therapy but exhibited complete recovery after extracorporeal blood purification with CytoSorb (CytoSorbents, Monmouth Junction, NJ). Six days after chimeric antigen receptor T-cell therapy infusion, the patient developed cytokine release syndrome grade 3, prompting administration of dexamethasone and tocilizumab, a monoclonal antibody against the interleukin-6 receptor. His C-reactive protein levels started to decrease with tocilizumab and dexamethasone treatments. However, his ferritin levels continued to rise, and his interleukin-6 levels were above the upper detection threshold. Thirty-six hours later, the patient showed improved cytokine release syndrome but developed severe immune effector cell-associated neurotoxicity syndrome with predominant encephalopathy (grade 3) despite treatment with dexamethasone/methylprednisolone, tocilizumab, and anakinra. We therefore sought a rescue strategy to remove inflammatory mediators. Following emergency use authorization, we initiated extracorporeal blood purification with CytoSorb (CytoSorbents). Four-day extracorporeal blood purification resulted in complete resolution of immune effector cell-associated neurotoxicity syndrome and greater than 95% reduction in interleukin-6 levels without side effects. The patient was discharged home 10 days later with no signs of neurotoxicity or other secondary end-organ dysfunction. CONCLUSIONS: Our case represents the first reported, successful application of extracorporeal blood purification with CytoSorb (CytoSorbents) to treat severe, refractory neurotoxicity following chimeric antigen receptor T-cell therapy. Lippincott Williams & Wilkins 2021-06-29 /pmc/articles/PMC8245117/ /pubmed/34235458 http://dx.doi.org/10.1097/CCE.0000000000000472 Text en Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine. https://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) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , 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.
spellingShingle Case Report
Singbartl, Kai
Rosenthal, Allison
Leis, Jose
Patel, Bhavesh
Sen, Ayan
Novel Use of Extracorporeal Blood Purification for Treatment of Severe, Refractory Neurotoxicity After Chimeric Antigen Receptor T-Cell Therapy—A Case Report
title Novel Use of Extracorporeal Blood Purification for Treatment of Severe, Refractory Neurotoxicity After Chimeric Antigen Receptor T-Cell Therapy—A Case Report
title_full Novel Use of Extracorporeal Blood Purification for Treatment of Severe, Refractory Neurotoxicity After Chimeric Antigen Receptor T-Cell Therapy—A Case Report
title_fullStr Novel Use of Extracorporeal Blood Purification for Treatment of Severe, Refractory Neurotoxicity After Chimeric Antigen Receptor T-Cell Therapy—A Case Report
title_full_unstemmed Novel Use of Extracorporeal Blood Purification for Treatment of Severe, Refractory Neurotoxicity After Chimeric Antigen Receptor T-Cell Therapy—A Case Report
title_short Novel Use of Extracorporeal Blood Purification for Treatment of Severe, Refractory Neurotoxicity After Chimeric Antigen Receptor T-Cell Therapy—A Case Report
title_sort novel use of extracorporeal blood purification for treatment of severe, refractory neurotoxicity after chimeric antigen receptor t-cell therapy—a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245117/
https://www.ncbi.nlm.nih.gov/pubmed/34235458
http://dx.doi.org/10.1097/CCE.0000000000000472
work_keys_str_mv AT singbartlkai noveluseofextracorporealbloodpurificationfortreatmentofsevererefractoryneurotoxicityafterchimericantigenreceptortcelltherapyacasereport
AT rosenthalallison noveluseofextracorporealbloodpurificationfortreatmentofsevererefractoryneurotoxicityafterchimericantigenreceptortcelltherapyacasereport
AT leisjose noveluseofextracorporealbloodpurificationfortreatmentofsevererefractoryneurotoxicityafterchimericantigenreceptortcelltherapyacasereport
AT patelbhavesh noveluseofextracorporealbloodpurificationfortreatmentofsevererefractoryneurotoxicityafterchimericantigenreceptortcelltherapyacasereport
AT senayan noveluseofextracorporealbloodpurificationfortreatmentofsevererefractoryneurotoxicityafterchimericantigenreceptortcelltherapyacasereport