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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...

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Autores principales: 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
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
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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.
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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
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