Cargando…
CD19-directed CAR T-cell therapy for treatment of primary CNS lymphoma
CD19-directed chimeric antigen receptor (CD19CAR) T-cell therapy has been successful in treating several B-cell lineage malignancies, including B-cell non-Hodgkin lymphoma (NHL). This modality has not yet been extended to NHL manifesting in the central nervous system (CNS), primarily as a result of...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Hematology
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945630/ https://www.ncbi.nlm.nih.gov/pubmed/34492703 http://dx.doi.org/10.1182/bloodadvances.2020004106 |
_version_ | 1784673999605727232 |
---|---|
author | Siddiqi, Tanya Wang, Xiuli Blanchard, M. Suzette Wagner, Jamie R. Popplewell, Leslie L. Budde, L. Elizabeth Stiller, Tracey L. Clark, Mary C. Lim, Laura Vyas, Vibhuti Brown, Christine E. Forman, Stephen J. |
author_facet | Siddiqi, Tanya Wang, Xiuli Blanchard, M. Suzette Wagner, Jamie R. Popplewell, Leslie L. Budde, L. Elizabeth Stiller, Tracey L. Clark, Mary C. Lim, Laura Vyas, Vibhuti Brown, Christine E. Forman, Stephen J. |
author_sort | Siddiqi, Tanya |
collection | PubMed |
description | CD19-directed chimeric antigen receptor (CD19CAR) T-cell therapy has been successful in treating several B-cell lineage malignancies, including B-cell non-Hodgkin lymphoma (NHL). This modality has not yet been extended to NHL manifesting in the central nervous system (CNS), primarily as a result of concerns for potential toxicity. CD19CAR T cells administered IV are detectable in cerebrospinal fluid (CSF), suggesting that chimeric antigen receptor (CAR) T cells can migrate from the periphery into the CNS, where they can potentially mediate antilymphoma activity. Here, we report the outcome of a subset of patients with primary CNS lymphoma (PCNSL; n = 5) who were treated with CD19CAR T cells in our ongoing phase 1 clinical trial. All patients developed grade ≥ 1 cytokine release syndrome and neurotoxicity post-CAR T-cell infusion; toxicities were reversible and tolerable, and there were no treatment-related deaths. At initial disease response, 3 of 5 patients (60%; 90% confidence interval, 19-92%) seemed to achieve complete remission, as indicated by resolution of enhancing brain lesions; the remaining 2 patients had stable disease. Although the study cohort was small, we demonstrate that using CD19CAR T cells to treat PCNSL can be safe and feasible. This trial was registered at www.clinicaltrials.gov as #NCT02153580. |
format | Online Article Text |
id | pubmed-8945630 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-89456302022-03-29 CD19-directed CAR T-cell therapy for treatment of primary CNS lymphoma Siddiqi, Tanya Wang, Xiuli Blanchard, M. Suzette Wagner, Jamie R. Popplewell, Leslie L. Budde, L. Elizabeth Stiller, Tracey L. Clark, Mary C. Lim, Laura Vyas, Vibhuti Brown, Christine E. Forman, Stephen J. Blood Adv Stimulus Report CD19-directed chimeric antigen receptor (CD19CAR) T-cell therapy has been successful in treating several B-cell lineage malignancies, including B-cell non-Hodgkin lymphoma (NHL). This modality has not yet been extended to NHL manifesting in the central nervous system (CNS), primarily as a result of concerns for potential toxicity. CD19CAR T cells administered IV are detectable in cerebrospinal fluid (CSF), suggesting that chimeric antigen receptor (CAR) T cells can migrate from the periphery into the CNS, where they can potentially mediate antilymphoma activity. Here, we report the outcome of a subset of patients with primary CNS lymphoma (PCNSL; n = 5) who were treated with CD19CAR T cells in our ongoing phase 1 clinical trial. All patients developed grade ≥ 1 cytokine release syndrome and neurotoxicity post-CAR T-cell infusion; toxicities were reversible and tolerable, and there were no treatment-related deaths. At initial disease response, 3 of 5 patients (60%; 90% confidence interval, 19-92%) seemed to achieve complete remission, as indicated by resolution of enhancing brain lesions; the remaining 2 patients had stable disease. Although the study cohort was small, we demonstrate that using CD19CAR T cells to treat PCNSL can be safe and feasible. This trial was registered at www.clinicaltrials.gov as #NCT02153580. American Society of Hematology 2021-10-20 /pmc/articles/PMC8945630/ /pubmed/34492703 http://dx.doi.org/10.1182/bloodadvances.2020004106 Text en © 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. |
spellingShingle | Stimulus Report Siddiqi, Tanya Wang, Xiuli Blanchard, M. Suzette Wagner, Jamie R. Popplewell, Leslie L. Budde, L. Elizabeth Stiller, Tracey L. Clark, Mary C. Lim, Laura Vyas, Vibhuti Brown, Christine E. Forman, Stephen J. CD19-directed CAR T-cell therapy for treatment of primary CNS lymphoma |
title | CD19-directed CAR T-cell therapy for treatment of primary CNS lymphoma |
title_full | CD19-directed CAR T-cell therapy for treatment of primary CNS lymphoma |
title_fullStr | CD19-directed CAR T-cell therapy for treatment of primary CNS lymphoma |
title_full_unstemmed | CD19-directed CAR T-cell therapy for treatment of primary CNS lymphoma |
title_short | CD19-directed CAR T-cell therapy for treatment of primary CNS lymphoma |
title_sort | cd19-directed car t-cell therapy for treatment of primary cns lymphoma |
topic | Stimulus Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945630/ https://www.ncbi.nlm.nih.gov/pubmed/34492703 http://dx.doi.org/10.1182/bloodadvances.2020004106 |
work_keys_str_mv | AT siddiqitanya cd19directedcartcelltherapyfortreatmentofprimarycnslymphoma AT wangxiuli cd19directedcartcelltherapyfortreatmentofprimarycnslymphoma AT blanchardmsuzette cd19directedcartcelltherapyfortreatmentofprimarycnslymphoma AT wagnerjamier cd19directedcartcelltherapyfortreatmentofprimarycnslymphoma AT popplewelllesliel cd19directedcartcelltherapyfortreatmentofprimarycnslymphoma AT buddelelizabeth cd19directedcartcelltherapyfortreatmentofprimarycnslymphoma AT stillertraceyl cd19directedcartcelltherapyfortreatmentofprimarycnslymphoma AT clarkmaryc cd19directedcartcelltherapyfortreatmentofprimarycnslymphoma AT limlaura cd19directedcartcelltherapyfortreatmentofprimarycnslymphoma AT vyasvibhuti cd19directedcartcelltherapyfortreatmentofprimarycnslymphoma AT brownchristinee cd19directedcartcelltherapyfortreatmentofprimarycnslymphoma AT formanstephenj cd19directedcartcelltherapyfortreatmentofprimarycnslymphoma |