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Toxicity and efficacy of chimeric antigen receptor T-cell therapy in patients with diffuse large B-cell lymphoma above the age of 70 years compared to younger patients – a matched control multicenter cohort study

Data regarding efficacy and toxicity of chimeric antigen receptor T (CAR-T) cell therapy in the elderly, geriatric population are insufficient. In 2019, tisagenlecleucel and axicabtagene-ciloleucel were commercially approved for relapsed/refractory diffuse large B-cell lymphoma. From May 2019 onward...

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Autores principales: Ram, Ron, Grisariu, Sigal, Shargian-Alon, Liat, Amit, Odelia, Bar-On, Yaeli, Stepensky, Polina, Yeshurun, Moshe, Avni, Batia, Hagin, David, Perry, Chava, Gurion, Ronit, Sarid, Nadav, Herishanu, Yair, Gold, Ronit, Glait-Santar, Chen, Kay, Sigi, Avivi, Irit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052918/
https://www.ncbi.nlm.nih.gov/pubmed/34233446
http://dx.doi.org/10.3324/haematol.2021.278288
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author Ram, Ron
Grisariu, Sigal
Shargian-Alon, Liat
Amit, Odelia
Bar-On, Yaeli
Stepensky, Polina
Yeshurun, Moshe
Avni, Batia
Hagin, David
Perry, Chava
Gurion, Ronit
Sarid, Nadav
Herishanu, Yair
Gold, Ronit
Glait-Santar, Chen
Kay, Sigi
Avivi, Irit
author_facet Ram, Ron
Grisariu, Sigal
Shargian-Alon, Liat
Amit, Odelia
Bar-On, Yaeli
Stepensky, Polina
Yeshurun, Moshe
Avni, Batia
Hagin, David
Perry, Chava
Gurion, Ronit
Sarid, Nadav
Herishanu, Yair
Gold, Ronit
Glait-Santar, Chen
Kay, Sigi
Avivi, Irit
author_sort Ram, Ron
collection PubMed
description Data regarding efficacy and toxicity of chimeric antigen receptor T (CAR-T) cell therapy in the elderly, geriatric population are insufficient. In 2019, tisagenlecleucel and axicabtagene-ciloleucel were commercially approved for relapsed/refractory diffuse large B-cell lymphoma. From May 2019 onwards, 47 relapsed/refractory diffuse large Bcell lymphoma patients, ≥70 years underwent lymphopharesis in three Israeli centers. Elderly (n=41, mean age 76.2 years) and young (n=41, mean age 55.4 years) patients were matched based on ECOG performance status and lactose dehydrogenase levels. There were no differences in CD4/CD8 ratio (P=0.94), %CD4 naive (P=0.92), %CD8 naive (P=0.44) and exhaustion markers (both HLA-DR and PD-1) between CAR-T cell products in both cohorts. Forty-one elderly patients (87%) received CAR-T cell infusion. There were no differences in the incidence of grade ≥3 cytokine-release-syndrome (P=0.29), grade≥3 neurotoxicity (P=0.54), and duration of hospitalization (P=0.55) between elderly and younger patients. There was no difference in median D7-CAR-T cell expansion (P=0.145). Response rates were similar between the two groups (complete response 46% and partial response 17% in the elderly group, P=0.337). Non-relapse mortality at 1 and 3 months was 0 in both groups. With a median follow-up of 7 months (range, 1.3-17.2 months), 6- and 12-months progression-free and overall survival in elderly patients were 39% and 32%, and 74% and 69%, respectively. EORTC QLQ-C30 questionnaires, obtained at 1 month, showed worsening of disability and cancer-related-symptoms in elderly versus younger patients. We conclude that outcomes of CAR-T cell therapy are comparable between elderly, geriatric and younger patients, indicating that age as per se should not preclude CAR-T cell administration. Longer rehabilitation therapy is essential to improve disabilities and long-term symptoms.
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spelling pubmed-90529182022-05-13 Toxicity and efficacy of chimeric antigen receptor T-cell therapy in patients with diffuse large B-cell lymphoma above the age of 70 years compared to younger patients – a matched control multicenter cohort study Ram, Ron Grisariu, Sigal Shargian-Alon, Liat Amit, Odelia Bar-On, Yaeli Stepensky, Polina Yeshurun, Moshe Avni, Batia Hagin, David Perry, Chava Gurion, Ronit Sarid, Nadav Herishanu, Yair Gold, Ronit Glait-Santar, Chen Kay, Sigi Avivi, Irit Haematologica Article Data regarding efficacy and toxicity of chimeric antigen receptor T (CAR-T) cell therapy in the elderly, geriatric population are insufficient. In 2019, tisagenlecleucel and axicabtagene-ciloleucel were commercially approved for relapsed/refractory diffuse large B-cell lymphoma. From May 2019 onwards, 47 relapsed/refractory diffuse large Bcell lymphoma patients, ≥70 years underwent lymphopharesis in three Israeli centers. Elderly (n=41, mean age 76.2 years) and young (n=41, mean age 55.4 years) patients were matched based on ECOG performance status and lactose dehydrogenase levels. There were no differences in CD4/CD8 ratio (P=0.94), %CD4 naive (P=0.92), %CD8 naive (P=0.44) and exhaustion markers (both HLA-DR and PD-1) between CAR-T cell products in both cohorts. Forty-one elderly patients (87%) received CAR-T cell infusion. There were no differences in the incidence of grade ≥3 cytokine-release-syndrome (P=0.29), grade≥3 neurotoxicity (P=0.54), and duration of hospitalization (P=0.55) between elderly and younger patients. There was no difference in median D7-CAR-T cell expansion (P=0.145). Response rates were similar between the two groups (complete response 46% and partial response 17% in the elderly group, P=0.337). Non-relapse mortality at 1 and 3 months was 0 in both groups. With a median follow-up of 7 months (range, 1.3-17.2 months), 6- and 12-months progression-free and overall survival in elderly patients were 39% and 32%, and 74% and 69%, respectively. EORTC QLQ-C30 questionnaires, obtained at 1 month, showed worsening of disability and cancer-related-symptoms in elderly versus younger patients. We conclude that outcomes of CAR-T cell therapy are comparable between elderly, geriatric and younger patients, indicating that age as per se should not preclude CAR-T cell administration. Longer rehabilitation therapy is essential to improve disabilities and long-term symptoms. Fondazione Ferrata Storti 2021-07-08 /pmc/articles/PMC9052918/ /pubmed/34233446 http://dx.doi.org/10.3324/haematol.2021.278288 Text en Copyright© 2022 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
Ram, Ron
Grisariu, Sigal
Shargian-Alon, Liat
Amit, Odelia
Bar-On, Yaeli
Stepensky, Polina
Yeshurun, Moshe
Avni, Batia
Hagin, David
Perry, Chava
Gurion, Ronit
Sarid, Nadav
Herishanu, Yair
Gold, Ronit
Glait-Santar, Chen
Kay, Sigi
Avivi, Irit
Toxicity and efficacy of chimeric antigen receptor T-cell therapy in patients with diffuse large B-cell lymphoma above the age of 70 years compared to younger patients – a matched control multicenter cohort study
title Toxicity and efficacy of chimeric antigen receptor T-cell therapy in patients with diffuse large B-cell lymphoma above the age of 70 years compared to younger patients – a matched control multicenter cohort study
title_full Toxicity and efficacy of chimeric antigen receptor T-cell therapy in patients with diffuse large B-cell lymphoma above the age of 70 years compared to younger patients – a matched control multicenter cohort study
title_fullStr Toxicity and efficacy of chimeric antigen receptor T-cell therapy in patients with diffuse large B-cell lymphoma above the age of 70 years compared to younger patients – a matched control multicenter cohort study
title_full_unstemmed Toxicity and efficacy of chimeric antigen receptor T-cell therapy in patients with diffuse large B-cell lymphoma above the age of 70 years compared to younger patients – a matched control multicenter cohort study
title_short Toxicity and efficacy of chimeric antigen receptor T-cell therapy in patients with diffuse large B-cell lymphoma above the age of 70 years compared to younger patients – a matched control multicenter cohort study
title_sort toxicity and efficacy of chimeric antigen receptor t-cell therapy in patients with diffuse large b-cell lymphoma above the age of 70 years compared to younger patients – a matched control multicenter cohort study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052918/
https://www.ncbi.nlm.nih.gov/pubmed/34233446
http://dx.doi.org/10.3324/haematol.2021.278288
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