Cargando…
Early Use of Corticosteroids following CAR T-Cell Therapy Correlates with Reduced Risk of High-Grade CRS without Negative Impact on Neurotoxicity or Treatment Outcome
Background: Chimeric antigen receptor T-cell therapy (CAR T-cell therapy) is associated with potentially life-threatening toxicities, most commonly cytokine release syndrome (CRS) and immune-effector-cell-associated neurotoxicity syndrome (ICANS). These frequent adverse events are managed with the I...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953517/ https://www.ncbi.nlm.nih.gov/pubmed/36830750 http://dx.doi.org/10.3390/biom13020382 |
_version_ | 1784893897473785856 |
---|---|
author | Lakomy, Tim Akhoundova, Dilara Nilius, Henning Kronig, Marie-Noëlle Novak, Urban Daskalakis, Michael Bacher, Ulrike Pabst, Thomas |
author_facet | Lakomy, Tim Akhoundova, Dilara Nilius, Henning Kronig, Marie-Noëlle Novak, Urban Daskalakis, Michael Bacher, Ulrike Pabst, Thomas |
author_sort | Lakomy, Tim |
collection | PubMed |
description | Background: Chimeric antigen receptor T-cell therapy (CAR T-cell therapy) is associated with potentially life-threatening toxicities, most commonly cytokine release syndrome (CRS) and immune-effector-cell-associated neurotoxicity syndrome (ICANS). These frequent adverse events are managed with the IL-6 receptor antagonist tocilizumab and/or corticosteroids. The prophylactic and early use of corticosteroids for CRS and ICANS have previously been reported, but eventual negative impacts on CAR T-cell efficacy are feared. Methods: Retrospective comparative analysis of two patient cohorts with hematological malignancies treated with CAR T-cell therapy: 43 patients received early administration of 10 mg dexamethasone preceding each dose of tocilizumab (“early corticosteroid/ tocilizumab”, EcsTcz cohort) vs. 40 patients who received tocilizumab alone (“tocilizumab alone”, Tcz cohort) for treatment of low-grade CRS. Results: Despite overall higher CRS incidence (91% vs. 70%; p = 0.0249), no high-grade CRS was observed (0% vs. 10%; p = 0.0497) among patients receiving early corticosteroids in combination with tocilizumab. In terms of neurotoxicity, no worsening regarding incidence of ICANS (30% vs. 33%; p = 0.8177) or high-grade ICANS (20% vs. 14%; p = 0.5624) was observed in the EcsTcz cohort. Moreover, overall response rates (80% vs. 77%; p = 0.7936), complete response rates (50% vs. 44%; p = 0.6628), progression-free survival (p = 0.6345) and overall survival (p = 0.1215) were comparable for both cohorts. Conclusions: Our study suggests that the early use of corticosteroids in combination with the standard tocilizumab schedule for low-grade CRS following CAR T-cell therapy may significantly reduce the risk of high-grade CRS without negative impact on neurotoxicity or treatment outcome. |
format | Online Article Text |
id | pubmed-9953517 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99535172023-02-25 Early Use of Corticosteroids following CAR T-Cell Therapy Correlates with Reduced Risk of High-Grade CRS without Negative Impact on Neurotoxicity or Treatment Outcome Lakomy, Tim Akhoundova, Dilara Nilius, Henning Kronig, Marie-Noëlle Novak, Urban Daskalakis, Michael Bacher, Ulrike Pabst, Thomas Biomolecules Article Background: Chimeric antigen receptor T-cell therapy (CAR T-cell therapy) is associated with potentially life-threatening toxicities, most commonly cytokine release syndrome (CRS) and immune-effector-cell-associated neurotoxicity syndrome (ICANS). These frequent adverse events are managed with the IL-6 receptor antagonist tocilizumab and/or corticosteroids. The prophylactic and early use of corticosteroids for CRS and ICANS have previously been reported, but eventual negative impacts on CAR T-cell efficacy are feared. Methods: Retrospective comparative analysis of two patient cohorts with hematological malignancies treated with CAR T-cell therapy: 43 patients received early administration of 10 mg dexamethasone preceding each dose of tocilizumab (“early corticosteroid/ tocilizumab”, EcsTcz cohort) vs. 40 patients who received tocilizumab alone (“tocilizumab alone”, Tcz cohort) for treatment of low-grade CRS. Results: Despite overall higher CRS incidence (91% vs. 70%; p = 0.0249), no high-grade CRS was observed (0% vs. 10%; p = 0.0497) among patients receiving early corticosteroids in combination with tocilizumab. In terms of neurotoxicity, no worsening regarding incidence of ICANS (30% vs. 33%; p = 0.8177) or high-grade ICANS (20% vs. 14%; p = 0.5624) was observed in the EcsTcz cohort. Moreover, overall response rates (80% vs. 77%; p = 0.7936), complete response rates (50% vs. 44%; p = 0.6628), progression-free survival (p = 0.6345) and overall survival (p = 0.1215) were comparable for both cohorts. Conclusions: Our study suggests that the early use of corticosteroids in combination with the standard tocilizumab schedule for low-grade CRS following CAR T-cell therapy may significantly reduce the risk of high-grade CRS without negative impact on neurotoxicity or treatment outcome. MDPI 2023-02-17 /pmc/articles/PMC9953517/ /pubmed/36830750 http://dx.doi.org/10.3390/biom13020382 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 | Article Lakomy, Tim Akhoundova, Dilara Nilius, Henning Kronig, Marie-Noëlle Novak, Urban Daskalakis, Michael Bacher, Ulrike Pabst, Thomas Early Use of Corticosteroids following CAR T-Cell Therapy Correlates with Reduced Risk of High-Grade CRS without Negative Impact on Neurotoxicity or Treatment Outcome |
title | Early Use of Corticosteroids following CAR T-Cell Therapy Correlates with Reduced Risk of High-Grade CRS without Negative Impact on Neurotoxicity or Treatment Outcome |
title_full | Early Use of Corticosteroids following CAR T-Cell Therapy Correlates with Reduced Risk of High-Grade CRS without Negative Impact on Neurotoxicity or Treatment Outcome |
title_fullStr | Early Use of Corticosteroids following CAR T-Cell Therapy Correlates with Reduced Risk of High-Grade CRS without Negative Impact on Neurotoxicity or Treatment Outcome |
title_full_unstemmed | Early Use of Corticosteroids following CAR T-Cell Therapy Correlates with Reduced Risk of High-Grade CRS without Negative Impact on Neurotoxicity or Treatment Outcome |
title_short | Early Use of Corticosteroids following CAR T-Cell Therapy Correlates with Reduced Risk of High-Grade CRS without Negative Impact on Neurotoxicity or Treatment Outcome |
title_sort | early use of corticosteroids following car t-cell therapy correlates with reduced risk of high-grade crs without negative impact on neurotoxicity or treatment outcome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953517/ https://www.ncbi.nlm.nih.gov/pubmed/36830750 http://dx.doi.org/10.3390/biom13020382 |
work_keys_str_mv | AT lakomytim earlyuseofcorticosteroidsfollowingcartcelltherapycorrelateswithreducedriskofhighgradecrswithoutnegativeimpactonneurotoxicityortreatmentoutcome AT akhoundovadilara earlyuseofcorticosteroidsfollowingcartcelltherapycorrelateswithreducedriskofhighgradecrswithoutnegativeimpactonneurotoxicityortreatmentoutcome AT niliushenning earlyuseofcorticosteroidsfollowingcartcelltherapycorrelateswithreducedriskofhighgradecrswithoutnegativeimpactonneurotoxicityortreatmentoutcome AT kronigmarienoelle earlyuseofcorticosteroidsfollowingcartcelltherapycorrelateswithreducedriskofhighgradecrswithoutnegativeimpactonneurotoxicityortreatmentoutcome AT novakurban earlyuseofcorticosteroidsfollowingcartcelltherapycorrelateswithreducedriskofhighgradecrswithoutnegativeimpactonneurotoxicityortreatmentoutcome AT daskalakismichael earlyuseofcorticosteroidsfollowingcartcelltherapycorrelateswithreducedriskofhighgradecrswithoutnegativeimpactonneurotoxicityortreatmentoutcome AT bacherulrike earlyuseofcorticosteroidsfollowingcartcelltherapycorrelateswithreducedriskofhighgradecrswithoutnegativeimpactonneurotoxicityortreatmentoutcome AT pabstthomas earlyuseofcorticosteroidsfollowingcartcelltherapycorrelateswithreducedriskofhighgradecrswithoutnegativeimpactonneurotoxicityortreatmentoutcome |