Cargando…

Molecular and Clinical Characteristics of Different Toxicity Rates in Anti-CD19 Chimeric Antigen Receptor T Cells: Real-World Experience

SIMPLE SUMMARY: Our real-world experience confirmed that commercial CART therapy can be administered with minimal toxicity. The early referral of patients with low tumor burdens is important as CAR T indications continue to expand. Furthermore, close monitoring and the early recognition of side effe...

Descripción completa

Detalles Bibliográficos
Autores principales: Gavriilaki, E., Mallouri, D., Bousiou, Z., Demosthenous, C., Vardi, A., Dolgyras, P., Batsis, I., Stroggyli, E., Karvouni, P., Masmanidou, M., Gavriilaki, M., Bouinta, A., Bitsianis, S., Kapravelos, N., Bitzani, M., Vasileiadou, G., Yannaki, E., Sotiropoulos, D., Papagiannopoulos, S., Kazis, D., Kimiskidis, V., Anagnostopoulos, A., Sakellari, I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487155/
https://www.ncbi.nlm.nih.gov/pubmed/37686529
http://dx.doi.org/10.3390/cancers15174253
_version_ 1785103171902767104
author Gavriilaki, E.
Mallouri, D.
Bousiou, Z.
Demosthenous, C.
Vardi, A.
Dolgyras, P.
Batsis, I.
Stroggyli, E.
Karvouni, P.
Masmanidou, M.
Gavriilaki, M.
Bouinta, A.
Bitsianis, S.
Kapravelos, N.
Bitzani, M.
Vasileiadou, G.
Yannaki, E.
Sotiropoulos, D.
Papagiannopoulos, S.
Kazis, D.
Kimiskidis, V.
Anagnostopoulos, A.
Sakellari, I.
author_facet Gavriilaki, E.
Mallouri, D.
Bousiou, Z.
Demosthenous, C.
Vardi, A.
Dolgyras, P.
Batsis, I.
Stroggyli, E.
Karvouni, P.
Masmanidou, M.
Gavriilaki, M.
Bouinta, A.
Bitsianis, S.
Kapravelos, N.
Bitzani, M.
Vasileiadou, G.
Yannaki, E.
Sotiropoulos, D.
Papagiannopoulos, S.
Kazis, D.
Kimiskidis, V.
Anagnostopoulos, A.
Sakellari, I.
author_sort Gavriilaki, E.
collection PubMed
description SIMPLE SUMMARY: Our real-world experience confirmed that commercial CART therapy can be administered with minimal toxicity. The early referral of patients with low tumor burdens is important as CAR T indications continue to expand. Furthermore, close monitoring and the early recognition of side effects are beneficial to preventing major toxicities and may potentially expand the use of CAR T therapy. ABSTRACT: Commercially available anti-CD19 chimeric antigen receptor T cells (CARΤ cells) have offered long-term survival to a constantly expanding patient population. Given that novel toxicities including cytokine release syndrome (CRS) and neurotoxicity (ICANS) have been observed, we aimed to document the safety and toxicity of this treatment in a real-world study. We enrolled 31 adult patients referred to our center for CAR T therapy. Tisagenlecleucel was infused in 12 patients, axicabtagene ciloleucel in 14, and brexucabtagene autoleucel in 5. Cytokine release syndrome was noted in 26 patients while neurotoxicity was observed in 7. Tocilizumab was administered for CRS in 18 patients, along with short-term, low-dose steroid administration in one patient who developed grade III CRS and, subsequently, grade I ICANS. High-dose steroids, along with anakinra and siltuximab, were administered in only two MCL patients. With a median follow-up time of 13.4 months, nine patients were then in CR. The progression-free (PFS) and overall survival (OS) rates were 41.2% and 88.1% at one year, respectively. MCL diagnosis, which coincides with the administration of brexucabtagene autoleucel, was the only factor to be independently associated with poor OS (p < 0.001); meanwhile, increased LDH independently predicted PFS (p = 0.027).In addition, CRP at day 14 was associated with a poor OS (p = 0.001). Therefore, our real-world experience confirmed that commercial CAR T therapy can be administered with minimal toxicity.
format Online
Article
Text
id pubmed-10487155
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-104871552023-09-09 Molecular and Clinical Characteristics of Different Toxicity Rates in Anti-CD19 Chimeric Antigen Receptor T Cells: Real-World Experience Gavriilaki, E. Mallouri, D. Bousiou, Z. Demosthenous, C. Vardi, A. Dolgyras, P. Batsis, I. Stroggyli, E. Karvouni, P. Masmanidou, M. Gavriilaki, M. Bouinta, A. Bitsianis, S. Kapravelos, N. Bitzani, M. Vasileiadou, G. Yannaki, E. Sotiropoulos, D. Papagiannopoulos, S. Kazis, D. Kimiskidis, V. Anagnostopoulos, A. Sakellari, I. Cancers (Basel) Article SIMPLE SUMMARY: Our real-world experience confirmed that commercial CART therapy can be administered with minimal toxicity. The early referral of patients with low tumor burdens is important as CAR T indications continue to expand. Furthermore, close monitoring and the early recognition of side effects are beneficial to preventing major toxicities and may potentially expand the use of CAR T therapy. ABSTRACT: Commercially available anti-CD19 chimeric antigen receptor T cells (CARΤ cells) have offered long-term survival to a constantly expanding patient population. Given that novel toxicities including cytokine release syndrome (CRS) and neurotoxicity (ICANS) have been observed, we aimed to document the safety and toxicity of this treatment in a real-world study. We enrolled 31 adult patients referred to our center for CAR T therapy. Tisagenlecleucel was infused in 12 patients, axicabtagene ciloleucel in 14, and brexucabtagene autoleucel in 5. Cytokine release syndrome was noted in 26 patients while neurotoxicity was observed in 7. Tocilizumab was administered for CRS in 18 patients, along with short-term, low-dose steroid administration in one patient who developed grade III CRS and, subsequently, grade I ICANS. High-dose steroids, along with anakinra and siltuximab, were administered in only two MCL patients. With a median follow-up time of 13.4 months, nine patients were then in CR. The progression-free (PFS) and overall survival (OS) rates were 41.2% and 88.1% at one year, respectively. MCL diagnosis, which coincides with the administration of brexucabtagene autoleucel, was the only factor to be independently associated with poor OS (p < 0.001); meanwhile, increased LDH independently predicted PFS (p = 0.027).In addition, CRP at day 14 was associated with a poor OS (p = 0.001). Therefore, our real-world experience confirmed that commercial CAR T therapy can be administered with minimal toxicity. MDPI 2023-08-25 /pmc/articles/PMC10487155/ /pubmed/37686529 http://dx.doi.org/10.3390/cancers15174253 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
Gavriilaki, E.
Mallouri, D.
Bousiou, Z.
Demosthenous, C.
Vardi, A.
Dolgyras, P.
Batsis, I.
Stroggyli, E.
Karvouni, P.
Masmanidou, M.
Gavriilaki, M.
Bouinta, A.
Bitsianis, S.
Kapravelos, N.
Bitzani, M.
Vasileiadou, G.
Yannaki, E.
Sotiropoulos, D.
Papagiannopoulos, S.
Kazis, D.
Kimiskidis, V.
Anagnostopoulos, A.
Sakellari, I.
Molecular and Clinical Characteristics of Different Toxicity Rates in Anti-CD19 Chimeric Antigen Receptor T Cells: Real-World Experience
title Molecular and Clinical Characteristics of Different Toxicity Rates in Anti-CD19 Chimeric Antigen Receptor T Cells: Real-World Experience
title_full Molecular and Clinical Characteristics of Different Toxicity Rates in Anti-CD19 Chimeric Antigen Receptor T Cells: Real-World Experience
title_fullStr Molecular and Clinical Characteristics of Different Toxicity Rates in Anti-CD19 Chimeric Antigen Receptor T Cells: Real-World Experience
title_full_unstemmed Molecular and Clinical Characteristics of Different Toxicity Rates in Anti-CD19 Chimeric Antigen Receptor T Cells: Real-World Experience
title_short Molecular and Clinical Characteristics of Different Toxicity Rates in Anti-CD19 Chimeric Antigen Receptor T Cells: Real-World Experience
title_sort molecular and clinical characteristics of different toxicity rates in anti-cd19 chimeric antigen receptor t cells: real-world experience
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487155/
https://www.ncbi.nlm.nih.gov/pubmed/37686529
http://dx.doi.org/10.3390/cancers15174253
work_keys_str_mv AT gavriilakie molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT mallourid molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT bousiouz molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT demosthenousc molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT vardia molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT dolgyrasp molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT batsisi molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT stroggylie molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT karvounip molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT masmanidoum molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT gavriilakim molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT bouintaa molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT bitsianiss molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT kapravelosn molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT bitzanim molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT vasileiadoug molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT yannakie molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT sotiropoulosd molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT papagiannopouloss molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT kazisd molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT kimiskidisv molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT anagnostopoulosa molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience
AT sakellarii molecularandclinicalcharacteristicsofdifferenttoxicityratesinanticd19chimericantigenreceptortcellsrealworldexperience