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Single-center experience using anakinra for steroid-refractory immune effector cell-associated neurotoxicity syndrome (ICANS)

In addition to remarkable antitumor activity, chimeric antigen receptor (CAR) T-cell therapy is associated with acute toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Current treatment guidelines for CRS and ICANS include use of t...

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Autores principales: Wehrli, Marc, Gallagher, Kathleen, Chen, Yi-Bin, Leick, Mark B, McAfee, Steven L, El-Jawahri, Areej R, DeFilipp, Zachariah, Horick, Nora, O'Donnell, Paul, Spitzer, Thomas, Dey, Bimal, Cook, Daniella, Trailor, Michael, Lindell, Kevin, Maus, Marcela V, Frigault, Matthew J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8744112/
https://www.ncbi.nlm.nih.gov/pubmed/34996813
http://dx.doi.org/10.1136/jitc-2021-003847
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author Wehrli, Marc
Gallagher, Kathleen
Chen, Yi-Bin
Leick, Mark B
McAfee, Steven L
El-Jawahri, Areej R
DeFilipp, Zachariah
Horick, Nora
O'Donnell, Paul
Spitzer, Thomas
Dey, Bimal
Cook, Daniella
Trailor, Michael
Lindell, Kevin
Maus, Marcela V
Frigault, Matthew J
author_facet Wehrli, Marc
Gallagher, Kathleen
Chen, Yi-Bin
Leick, Mark B
McAfee, Steven L
El-Jawahri, Areej R
DeFilipp, Zachariah
Horick, Nora
O'Donnell, Paul
Spitzer, Thomas
Dey, Bimal
Cook, Daniella
Trailor, Michael
Lindell, Kevin
Maus, Marcela V
Frigault, Matthew J
author_sort Wehrli, Marc
collection PubMed
description In addition to remarkable antitumor activity, chimeric antigen receptor (CAR) T-cell therapy is associated with acute toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Current treatment guidelines for CRS and ICANS include use of tocilizumab, a monoclonal antibody that blocks the interleukin (IL)-6 receptor, and corticosteroids. In patients with refractory CRS, use of several other agents as third-line therapy (including siltuximab, ruxolitinib, anakinra, dasatinib, and cyclophosphamide) has been reported on an anecdotal basis. At our institution, anakinra has become the standard treatment for the management of steroid-refractory ICANS with or without CRS, based on recent animal data demonstrating the role of IL-1 in the pathogenesis of ICANS/CRS. Here, we retrospectively analyzed clinical and laboratory parameters, including serum cytokines, in 14 patients at our center treated with anakinra for steroid-refractory ICANS with or without CRS after standard treatment with tisagenlecleucel (Kymriah) or axicabtagene ciloleucel (Yescarta) CD19-targeting CAR T. We observed statistically significant and rapid reductions in fever, inflammatory cytokines, and biomarkers associated with ICANS/CRS after anakinra treatment. With three daily subcutaneous doses, anakinra did not have a clear, clinically dramatic effect on neurotoxicity, and its use did not result in rapid tapering of corticosteroids; although neutropenia and thrombocytopenia were common at the time of anakinra dosing, there were no clear delays in hematopoietic recovery or infections that were directly attributable to anakinra. Anakinra may be useful adjunct to steroids and tocilizumab in the management of CRS and/or steroid-refractory ICANs resulting from CAR T-cell therapies, but prospective studies are needed to determine its efficacy in these settings.
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spelling pubmed-87441122022-01-20 Single-center experience using anakinra for steroid-refractory immune effector cell-associated neurotoxicity syndrome (ICANS) Wehrli, Marc Gallagher, Kathleen Chen, Yi-Bin Leick, Mark B McAfee, Steven L El-Jawahri, Areej R DeFilipp, Zachariah Horick, Nora O'Donnell, Paul Spitzer, Thomas Dey, Bimal Cook, Daniella Trailor, Michael Lindell, Kevin Maus, Marcela V Frigault, Matthew J J Immunother Cancer Immune Cell Therapies and Immune Cell Engineering In addition to remarkable antitumor activity, chimeric antigen receptor (CAR) T-cell therapy is associated with acute toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Current treatment guidelines for CRS and ICANS include use of tocilizumab, a monoclonal antibody that blocks the interleukin (IL)-6 receptor, and corticosteroids. In patients with refractory CRS, use of several other agents as third-line therapy (including siltuximab, ruxolitinib, anakinra, dasatinib, and cyclophosphamide) has been reported on an anecdotal basis. At our institution, anakinra has become the standard treatment for the management of steroid-refractory ICANS with or without CRS, based on recent animal data demonstrating the role of IL-1 in the pathogenesis of ICANS/CRS. Here, we retrospectively analyzed clinical and laboratory parameters, including serum cytokines, in 14 patients at our center treated with anakinra for steroid-refractory ICANS with or without CRS after standard treatment with tisagenlecleucel (Kymriah) or axicabtagene ciloleucel (Yescarta) CD19-targeting CAR T. We observed statistically significant and rapid reductions in fever, inflammatory cytokines, and biomarkers associated with ICANS/CRS after anakinra treatment. With three daily subcutaneous doses, anakinra did not have a clear, clinically dramatic effect on neurotoxicity, and its use did not result in rapid tapering of corticosteroids; although neutropenia and thrombocytopenia were common at the time of anakinra dosing, there were no clear delays in hematopoietic recovery or infections that were directly attributable to anakinra. Anakinra may be useful adjunct to steroids and tocilizumab in the management of CRS and/or steroid-refractory ICANs resulting from CAR T-cell therapies, but prospective studies are needed to determine its efficacy in these settings. BMJ Publishing Group 2022-01-07 /pmc/articles/PMC8744112/ /pubmed/34996813 http://dx.doi.org/10.1136/jitc-2021-003847 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See https://creativecommons.org/licenses/by/4.0/.
spellingShingle Immune Cell Therapies and Immune Cell Engineering
Wehrli, Marc
Gallagher, Kathleen
Chen, Yi-Bin
Leick, Mark B
McAfee, Steven L
El-Jawahri, Areej R
DeFilipp, Zachariah
Horick, Nora
O'Donnell, Paul
Spitzer, Thomas
Dey, Bimal
Cook, Daniella
Trailor, Michael
Lindell, Kevin
Maus, Marcela V
Frigault, Matthew J
Single-center experience using anakinra for steroid-refractory immune effector cell-associated neurotoxicity syndrome (ICANS)
title Single-center experience using anakinra for steroid-refractory immune effector cell-associated neurotoxicity syndrome (ICANS)
title_full Single-center experience using anakinra for steroid-refractory immune effector cell-associated neurotoxicity syndrome (ICANS)
title_fullStr Single-center experience using anakinra for steroid-refractory immune effector cell-associated neurotoxicity syndrome (ICANS)
title_full_unstemmed Single-center experience using anakinra for steroid-refractory immune effector cell-associated neurotoxicity syndrome (ICANS)
title_short Single-center experience using anakinra for steroid-refractory immune effector cell-associated neurotoxicity syndrome (ICANS)
title_sort single-center experience using anakinra for steroid-refractory immune effector cell-associated neurotoxicity syndrome (icans)
topic Immune Cell Therapies and Immune Cell Engineering
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8744112/
https://www.ncbi.nlm.nih.gov/pubmed/34996813
http://dx.doi.org/10.1136/jitc-2021-003847
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