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Hematopoietic recovery and immune reconstitution after axicabtagene ciloleucel in patients with large B-cell lymphoma

Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 may be associated with long-term adverse effects such as cytopenia and immune deficiency. In order to characterize these late events, we analyzed 31 patients with relapsed or refractory large B-cell lymphoma treated with axicabtagene cilo...

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Autores principales: Strati, Paolo, Varma, Ankur, Adkins, Sherry, Nastoupil, Loretta J., Westin, Jason R., Hagemeister, Fredrick B, Fowler, Nathan H, Lee, Hun J., Fayad, Luis E., Samaniego, Felipe, Ahmed, Sairah, Chen, Yiming, Horowitz, Sandra, Arafat, Sara, Johncy, Swapna, Kebriaei, Partow, Mulanovich, Victor Eduardo, Heredia, Ella Ariza, Neelapu, Sattva S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485681/
https://www.ncbi.nlm.nih.gov/pubmed/32732355
http://dx.doi.org/10.3324/haematol.2020.254045
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author Strati, Paolo
Varma, Ankur
Adkins, Sherry
Nastoupil, Loretta J.
Westin, Jason R.
Hagemeister, Fredrick B
Fowler, Nathan H
Lee, Hun J.
Fayad, Luis E.
Samaniego, Felipe
Ahmed, Sairah
Chen, Yiming
Horowitz, Sandra
Arafat, Sara
Johncy, Swapna
Kebriaei, Partow
Mulanovich, Victor Eduardo
Heredia, Ella Ariza
Neelapu, Sattva S.
author_facet Strati, Paolo
Varma, Ankur
Adkins, Sherry
Nastoupil, Loretta J.
Westin, Jason R.
Hagemeister, Fredrick B
Fowler, Nathan H
Lee, Hun J.
Fayad, Luis E.
Samaniego, Felipe
Ahmed, Sairah
Chen, Yiming
Horowitz, Sandra
Arafat, Sara
Johncy, Swapna
Kebriaei, Partow
Mulanovich, Victor Eduardo
Heredia, Ella Ariza
Neelapu, Sattva S.
author_sort Strati, Paolo
collection PubMed
description Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 may be associated with long-term adverse effects such as cytopenia and immune deficiency. In order to characterize these late events, we analyzed 31 patients with relapsed or refractory large B-cell lymphoma treated with axicabtagene ciloleucel at our institution on two clinical trials, ZUMA-1 (clinicaltrials gov. Identifier: NCT02348216) and ZUMA-9 (clinicaltrials gov. Identifier: NCT03153462). Complete blood counts, lymphocyte subsets, and immunoglobulin levels were measured serially until month 24 or progression. Fifteen (48%) patients had grade 3-4 cytopenia, including anemia (five, 16%), neutropenia (nine, 29%), or thrombocytopenia (13, 42%) at day 30. Cytopenia at day 30 was not significantly associated with later diagnosis of myelodysplasia. Among patients with ongoing remission, grade 3-4 cytopenia was observed in one of nine (11%) at 2 years. While peripheral CD8(+) T cells recovered early, CD4(+) T-cell recovery was delayed with a count of <200/mL in three of nine (33%) patients at 1 year and two of seven (29%) at 2 years. Immunoglobulin G levels normalized in five of nine (56%) patients at 2 years. Thirteen (42%) patients developed grade 3-4 infectious complications, including herpes zoster and Pneumocystis jiroveci pneumonia. These results suggest the need for prolonged monitoring and prophylaxis against opportunistic infections in these patients, to improve the longterm safety of axicabtagene ciloleucel therapy.
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spelling pubmed-84856812021-10-18 Hematopoietic recovery and immune reconstitution after axicabtagene ciloleucel in patients with large B-cell lymphoma Strati, Paolo Varma, Ankur Adkins, Sherry Nastoupil, Loretta J. Westin, Jason R. Hagemeister, Fredrick B Fowler, Nathan H Lee, Hun J. Fayad, Luis E. Samaniego, Felipe Ahmed, Sairah Chen, Yiming Horowitz, Sandra Arafat, Sara Johncy, Swapna Kebriaei, Partow Mulanovich, Victor Eduardo Heredia, Ella Ariza Neelapu, Sattva S. Haematologica Article Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 may be associated with long-term adverse effects such as cytopenia and immune deficiency. In order to characterize these late events, we analyzed 31 patients with relapsed or refractory large B-cell lymphoma treated with axicabtagene ciloleucel at our institution on two clinical trials, ZUMA-1 (clinicaltrials gov. Identifier: NCT02348216) and ZUMA-9 (clinicaltrials gov. Identifier: NCT03153462). Complete blood counts, lymphocyte subsets, and immunoglobulin levels were measured serially until month 24 or progression. Fifteen (48%) patients had grade 3-4 cytopenia, including anemia (five, 16%), neutropenia (nine, 29%), or thrombocytopenia (13, 42%) at day 30. Cytopenia at day 30 was not significantly associated with later diagnosis of myelodysplasia. Among patients with ongoing remission, grade 3-4 cytopenia was observed in one of nine (11%) at 2 years. While peripheral CD8(+) T cells recovered early, CD4(+) T-cell recovery was delayed with a count of <200/mL in three of nine (33%) patients at 1 year and two of seven (29%) at 2 years. Immunoglobulin G levels normalized in five of nine (56%) patients at 2 years. Thirteen (42%) patients developed grade 3-4 infectious complications, including herpes zoster and Pneumocystis jiroveci pneumonia. These results suggest the need for prolonged monitoring and prophylaxis against opportunistic infections in these patients, to improve the longterm safety of axicabtagene ciloleucel therapy. Fondazione Ferrata Storti 2020-07-30 /pmc/articles/PMC8485681/ /pubmed/32732355 http://dx.doi.org/10.3324/haematol.2020.254045 Text en Copyright© 2021 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article
Strati, Paolo
Varma, Ankur
Adkins, Sherry
Nastoupil, Loretta J.
Westin, Jason R.
Hagemeister, Fredrick B
Fowler, Nathan H
Lee, Hun J.
Fayad, Luis E.
Samaniego, Felipe
Ahmed, Sairah
Chen, Yiming
Horowitz, Sandra
Arafat, Sara
Johncy, Swapna
Kebriaei, Partow
Mulanovich, Victor Eduardo
Heredia, Ella Ariza
Neelapu, Sattva S.
Hematopoietic recovery and immune reconstitution after axicabtagene ciloleucel in patients with large B-cell lymphoma
title Hematopoietic recovery and immune reconstitution after axicabtagene ciloleucel in patients with large B-cell lymphoma
title_full Hematopoietic recovery and immune reconstitution after axicabtagene ciloleucel in patients with large B-cell lymphoma
title_fullStr Hematopoietic recovery and immune reconstitution after axicabtagene ciloleucel in patients with large B-cell lymphoma
title_full_unstemmed Hematopoietic recovery and immune reconstitution after axicabtagene ciloleucel in patients with large B-cell lymphoma
title_short Hematopoietic recovery and immune reconstitution after axicabtagene ciloleucel in patients with large B-cell lymphoma
title_sort hematopoietic recovery and immune reconstitution after axicabtagene ciloleucel in patients with large b-cell lymphoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485681/
https://www.ncbi.nlm.nih.gov/pubmed/32732355
http://dx.doi.org/10.3324/haematol.2020.254045
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