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Salvage radiotherapy in relapsed/refractory large B-cell lymphoma after failure of CAR T-cell therapy
Despite the success of CD19-targeted chimeric antigen receptor (CAR T)-cell therapy in patients with relapsed/refractory large B-cell lymphoma (LBCL), there is a need for effective salvage strategies post-CAR T-cell therapy failure. We conducted a multi-institutional retrospective study of patients...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Fondazione Ferrata Storti
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620597/ https://www.ncbi.nlm.nih.gov/pubmed/37317884 http://dx.doi.org/10.3324/haematol.2023.282804 |
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author | Ababneh, Hazim S. Ng, Andrea K. Frigault, Matthew J. Abramson, Jeremy S. Johnson, Patrick Connor Jacobson, Caron A. Patel, Chirayu G. |
author_facet | Ababneh, Hazim S. Ng, Andrea K. Frigault, Matthew J. Abramson, Jeremy S. Johnson, Patrick Connor Jacobson, Caron A. Patel, Chirayu G. |
author_sort | Ababneh, Hazim S. |
collection | PubMed |
description | Despite the success of CD19-targeted chimeric antigen receptor (CAR T)-cell therapy in patients with relapsed/refractory large B-cell lymphoma (LBCL), there is a need for effective salvage strategies post-CAR T-cell therapy failure. We conducted a multi-institutional retrospective study of patients who relapsed following CAR T-cell therapy (axicabtagene ciloleucel [axi-cel] or tisagenlecleucel [tisa-cel]) and received salvage therapies (radiation therapy [RT] alone, systemic therapy alone, or combined modality therapy [CMT]). A total of 120 patients with post-CAR T relapsed LBCL received salvage therapies (RT alone, 25 patients; CMT, 15 patients; systemic therapy alone, 80 patients). The median follow-up from CAR T-cell infusion was 10.2 months (interquartile range, 5.2-20.9 months). Failure occurred in previously involved sites prior to CAR T-cell therapy in 78% of patients (n=93). A total of 93 sites were irradiated in 54 patients who received any salvage RT post-CAR T failure. The median dose/fractionation were 30 Gy (range, 4-50.4 Gy) and 10 fractions (range, 1-28 fractions). The 1-year local control rate for the 81 assessable sites was 84%. On univariate analysis, the median overall survival (OS) from the start date of RT was significantly higher among patients who received comprehensive RT versus focal RT (19.1 months vs. 3.0 months; P=<0.001). Twenty-three of 29 patients who received comprehensive RT had limited-stage disease. Among these, there was no difference in median OS among the patients who received RT alone versus those who received RT followed by additional therapies (log-rank P=0.2). On multivariate survival analysis, achieving PR or CR post-CAR T (hazard ratio =0.5; 95% confidence interval: 0.3-0.9; P=0.01) was independently associated with superior OS. Our findings suggest that RT can provide local control for LBCL relapsed post-CAR T-cell therapy, particularly in patients with limited-stage relapsed disease treated with comprehensive RT. |
format | Online Article Text |
id | pubmed-10620597 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Fondazione Ferrata Storti |
record_format | MEDLINE/PubMed |
spelling | pubmed-106205972023-11-03 Salvage radiotherapy in relapsed/refractory large B-cell lymphoma after failure of CAR T-cell therapy Ababneh, Hazim S. Ng, Andrea K. Frigault, Matthew J. Abramson, Jeremy S. Johnson, Patrick Connor Jacobson, Caron A. Patel, Chirayu G. Haematologica Article - Cell Therapy & Immunotherapy Despite the success of CD19-targeted chimeric antigen receptor (CAR T)-cell therapy in patients with relapsed/refractory large B-cell lymphoma (LBCL), there is a need for effective salvage strategies post-CAR T-cell therapy failure. We conducted a multi-institutional retrospective study of patients who relapsed following CAR T-cell therapy (axicabtagene ciloleucel [axi-cel] or tisagenlecleucel [tisa-cel]) and received salvage therapies (radiation therapy [RT] alone, systemic therapy alone, or combined modality therapy [CMT]). A total of 120 patients with post-CAR T relapsed LBCL received salvage therapies (RT alone, 25 patients; CMT, 15 patients; systemic therapy alone, 80 patients). The median follow-up from CAR T-cell infusion was 10.2 months (interquartile range, 5.2-20.9 months). Failure occurred in previously involved sites prior to CAR T-cell therapy in 78% of patients (n=93). A total of 93 sites were irradiated in 54 patients who received any salvage RT post-CAR T failure. The median dose/fractionation were 30 Gy (range, 4-50.4 Gy) and 10 fractions (range, 1-28 fractions). The 1-year local control rate for the 81 assessable sites was 84%. On univariate analysis, the median overall survival (OS) from the start date of RT was significantly higher among patients who received comprehensive RT versus focal RT (19.1 months vs. 3.0 months; P=<0.001). Twenty-three of 29 patients who received comprehensive RT had limited-stage disease. Among these, there was no difference in median OS among the patients who received RT alone versus those who received RT followed by additional therapies (log-rank P=0.2). On multivariate survival analysis, achieving PR or CR post-CAR T (hazard ratio =0.5; 95% confidence interval: 0.3-0.9; P=0.01) was independently associated with superior OS. Our findings suggest that RT can provide local control for LBCL relapsed post-CAR T-cell therapy, particularly in patients with limited-stage relapsed disease treated with comprehensive RT. Fondazione Ferrata Storti 2023-06-15 /pmc/articles/PMC10620597/ /pubmed/37317884 http://dx.doi.org/10.3324/haematol.2023.282804 Text en Copyright© 2023 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 - Cell Therapy & Immunotherapy Ababneh, Hazim S. Ng, Andrea K. Frigault, Matthew J. Abramson, Jeremy S. Johnson, Patrick Connor Jacobson, Caron A. Patel, Chirayu G. Salvage radiotherapy in relapsed/refractory large B-cell lymphoma after failure of CAR T-cell therapy |
title | Salvage radiotherapy in relapsed/refractory large B-cell lymphoma after failure of CAR T-cell therapy |
title_full | Salvage radiotherapy in relapsed/refractory large B-cell lymphoma after failure of CAR T-cell therapy |
title_fullStr | Salvage radiotherapy in relapsed/refractory large B-cell lymphoma after failure of CAR T-cell therapy |
title_full_unstemmed | Salvage radiotherapy in relapsed/refractory large B-cell lymphoma after failure of CAR T-cell therapy |
title_short | Salvage radiotherapy in relapsed/refractory large B-cell lymphoma after failure of CAR T-cell therapy |
title_sort | salvage radiotherapy in relapsed/refractory large b-cell lymphoma after failure of car t-cell therapy |
topic | Article - Cell Therapy & Immunotherapy |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620597/ https://www.ncbi.nlm.nih.gov/pubmed/37317884 http://dx.doi.org/10.3324/haematol.2023.282804 |
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