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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...

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Autores principales: Ababneh, Hazim S., Ng, Andrea K., Frigault, Matthew J., Abramson, Jeremy S., Johnson, Patrick Connor, Jacobson, Caron A., Patel, Chirayu G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2023
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.
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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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