Cargando…
Case Report: Subtotal Lymphoid and Total Marrow Irradiation as Bridge Therapy to CD19-Directed CAR T Cells in a Chemorefractory DLBCL With Leukemic Involvement
CAR T cell therapy has transformed the salvage approach for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Maintaining disease control before CAR T cell infusion during product manufacturing (so-called bridging therapy) is an important step to optimizing outcome. Among possible bridg...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330448/ https://www.ncbi.nlm.nih.gov/pubmed/35911683 http://dx.doi.org/10.3389/fimmu.2022.934700 |
_version_ | 1784758163424149504 |
---|---|
author | Saldi, Simonetta Perriello, Vincenzo Maria Falini, Lorenza Ruggeri, Loredana Fulcheri, Christian Ciardelli, Sara Innocente, Alessandra Ballanti, Stelvio Baffa, Nicodemo Flenghi, Leonardo Pierini, Antonio Aristei, Cynthia Falini, Brunangelo |
author_facet | Saldi, Simonetta Perriello, Vincenzo Maria Falini, Lorenza Ruggeri, Loredana Fulcheri, Christian Ciardelli, Sara Innocente, Alessandra Ballanti, Stelvio Baffa, Nicodemo Flenghi, Leonardo Pierini, Antonio Aristei, Cynthia Falini, Brunangelo |
author_sort | Saldi, Simonetta |
collection | PubMed |
description | CAR T cell therapy has transformed the salvage approach for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Maintaining disease control before CAR T cell infusion during product manufacturing (so-called bridging therapy) is an important step to optimizing outcome. Among possible bridging therapies, radiation therapy (RT) represents a valuable option, particularly when the disease is limited. Here, we report for the first time on a patient with chemorefractory-transformed DLBCL showing nodal, extranodal, and massive bone marrow (BM) lymphoma infiltration associated with leukemic involvement, a successful bridge therapy to CD19-directed CAR T cell therapy by subtotal lymphoid/total marrow irradiation plus thiothepa followed by reinfusion of CD34+ autologous hematopoietic stem cells. Such a novel bridging regimen allowed a significant reduction of nodal and BM tumor volume while improving blood cell count before CAR T cell infusion. The PET-CT scan and BM evaluation performed at 1, 3, and 6 months after treatment showed complete remission of the disease. A relapse occurred at almost 1 year in lymph nodes because of CD19 antigen escape while the BM remained free of disease. This extended radiotherapy approach may be an effective bridging therapy for chemorefractory DLBCL patients eligible for CAR T cells who present with a high tumor burden, including massive BM involvement associated with leukemic involvement. This preliminary evidence is worth confirming in additional patients. |
format | Online Article Text |
id | pubmed-9330448 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93304482022-07-29 Case Report: Subtotal Lymphoid and Total Marrow Irradiation as Bridge Therapy to CD19-Directed CAR T Cells in a Chemorefractory DLBCL With Leukemic Involvement Saldi, Simonetta Perriello, Vincenzo Maria Falini, Lorenza Ruggeri, Loredana Fulcheri, Christian Ciardelli, Sara Innocente, Alessandra Ballanti, Stelvio Baffa, Nicodemo Flenghi, Leonardo Pierini, Antonio Aristei, Cynthia Falini, Brunangelo Front Immunol Immunology CAR T cell therapy has transformed the salvage approach for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Maintaining disease control before CAR T cell infusion during product manufacturing (so-called bridging therapy) is an important step to optimizing outcome. Among possible bridging therapies, radiation therapy (RT) represents a valuable option, particularly when the disease is limited. Here, we report for the first time on a patient with chemorefractory-transformed DLBCL showing nodal, extranodal, and massive bone marrow (BM) lymphoma infiltration associated with leukemic involvement, a successful bridge therapy to CD19-directed CAR T cell therapy by subtotal lymphoid/total marrow irradiation plus thiothepa followed by reinfusion of CD34+ autologous hematopoietic stem cells. Such a novel bridging regimen allowed a significant reduction of nodal and BM tumor volume while improving blood cell count before CAR T cell infusion. The PET-CT scan and BM evaluation performed at 1, 3, and 6 months after treatment showed complete remission of the disease. A relapse occurred at almost 1 year in lymph nodes because of CD19 antigen escape while the BM remained free of disease. This extended radiotherapy approach may be an effective bridging therapy for chemorefractory DLBCL patients eligible for CAR T cells who present with a high tumor burden, including massive BM involvement associated with leukemic involvement. This preliminary evidence is worth confirming in additional patients. Frontiers Media S.A. 2022-07-14 /pmc/articles/PMC9330448/ /pubmed/35911683 http://dx.doi.org/10.3389/fimmu.2022.934700 Text en Copyright © 2022 Saldi, Perriello, Falini, Ruggeri, Fulcheri, Ciardelli, Innocente, Ballanti, Baffa, Flenghi, Pierini, Aristei and Falini https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Saldi, Simonetta Perriello, Vincenzo Maria Falini, Lorenza Ruggeri, Loredana Fulcheri, Christian Ciardelli, Sara Innocente, Alessandra Ballanti, Stelvio Baffa, Nicodemo Flenghi, Leonardo Pierini, Antonio Aristei, Cynthia Falini, Brunangelo Case Report: Subtotal Lymphoid and Total Marrow Irradiation as Bridge Therapy to CD19-Directed CAR T Cells in a Chemorefractory DLBCL With Leukemic Involvement |
title | Case Report: Subtotal Lymphoid and Total Marrow Irradiation as Bridge Therapy to CD19-Directed CAR T Cells in a Chemorefractory DLBCL With Leukemic Involvement |
title_full | Case Report: Subtotal Lymphoid and Total Marrow Irradiation as Bridge Therapy to CD19-Directed CAR T Cells in a Chemorefractory DLBCL With Leukemic Involvement |
title_fullStr | Case Report: Subtotal Lymphoid and Total Marrow Irradiation as Bridge Therapy to CD19-Directed CAR T Cells in a Chemorefractory DLBCL With Leukemic Involvement |
title_full_unstemmed | Case Report: Subtotal Lymphoid and Total Marrow Irradiation as Bridge Therapy to CD19-Directed CAR T Cells in a Chemorefractory DLBCL With Leukemic Involvement |
title_short | Case Report: Subtotal Lymphoid and Total Marrow Irradiation as Bridge Therapy to CD19-Directed CAR T Cells in a Chemorefractory DLBCL With Leukemic Involvement |
title_sort | case report: subtotal lymphoid and total marrow irradiation as bridge therapy to cd19-directed car t cells in a chemorefractory dlbcl with leukemic involvement |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330448/ https://www.ncbi.nlm.nih.gov/pubmed/35911683 http://dx.doi.org/10.3389/fimmu.2022.934700 |
work_keys_str_mv | AT saldisimonetta casereportsubtotallymphoidandtotalmarrowirradiationasbridgetherapytocd19directedcartcellsinachemorefractorydlbclwithleukemicinvolvement AT perriellovincenzomaria casereportsubtotallymphoidandtotalmarrowirradiationasbridgetherapytocd19directedcartcellsinachemorefractorydlbclwithleukemicinvolvement AT falinilorenza casereportsubtotallymphoidandtotalmarrowirradiationasbridgetherapytocd19directedcartcellsinachemorefractorydlbclwithleukemicinvolvement AT ruggeriloredana casereportsubtotallymphoidandtotalmarrowirradiationasbridgetherapytocd19directedcartcellsinachemorefractorydlbclwithleukemicinvolvement AT fulcherichristian casereportsubtotallymphoidandtotalmarrowirradiationasbridgetherapytocd19directedcartcellsinachemorefractorydlbclwithleukemicinvolvement AT ciardellisara casereportsubtotallymphoidandtotalmarrowirradiationasbridgetherapytocd19directedcartcellsinachemorefractorydlbclwithleukemicinvolvement AT innocentealessandra casereportsubtotallymphoidandtotalmarrowirradiationasbridgetherapytocd19directedcartcellsinachemorefractorydlbclwithleukemicinvolvement AT ballantistelvio casereportsubtotallymphoidandtotalmarrowirradiationasbridgetherapytocd19directedcartcellsinachemorefractorydlbclwithleukemicinvolvement AT baffanicodemo casereportsubtotallymphoidandtotalmarrowirradiationasbridgetherapytocd19directedcartcellsinachemorefractorydlbclwithleukemicinvolvement AT flenghileonardo casereportsubtotallymphoidandtotalmarrowirradiationasbridgetherapytocd19directedcartcellsinachemorefractorydlbclwithleukemicinvolvement AT pieriniantonio casereportsubtotallymphoidandtotalmarrowirradiationasbridgetherapytocd19directedcartcellsinachemorefractorydlbclwithleukemicinvolvement AT aristeicynthia casereportsubtotallymphoidandtotalmarrowirradiationasbridgetherapytocd19directedcartcellsinachemorefractorydlbclwithleukemicinvolvement AT falinibrunangelo casereportsubtotallymphoidandtotalmarrowirradiationasbridgetherapytocd19directedcartcellsinachemorefractorydlbclwithleukemicinvolvement |