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ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia

Overcoming graft-versus-host disease (GvHD) without increasing relapse and severe infections is a major challenge after allogeneic hematopoietic stem-cell transplantation (HSCT). ATIR101 is a haploidentical, naïve cell-enriched T-cell product, depleted of recipient-alloreactive T cells to minimize t...

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Autores principales: Roy, Denis Claude, Walker, Irwin, Maertens, Johan, Lewalle, Philippe, Olavarria, Eduardo, Selleslag, Dominik, Lachance, Sylvie, Buyse, Marc, Wang, Kun, Rovers, Jeroen, Santi, Irene, Bonig, Halvard, Sandler, Andrew, Velthuis, Jurjen, Mielke, Stephan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326707/
https://www.ncbi.nlm.nih.gov/pubmed/32047237
http://dx.doi.org/10.1038/s41375-020-0733-0
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author Roy, Denis Claude
Walker, Irwin
Maertens, Johan
Lewalle, Philippe
Olavarria, Eduardo
Selleslag, Dominik
Lachance, Sylvie
Buyse, Marc
Wang, Kun
Rovers, Jeroen
Santi, Irene
Bonig, Halvard
Sandler, Andrew
Velthuis, Jurjen
Mielke, Stephan
author_facet Roy, Denis Claude
Walker, Irwin
Maertens, Johan
Lewalle, Philippe
Olavarria, Eduardo
Selleslag, Dominik
Lachance, Sylvie
Buyse, Marc
Wang, Kun
Rovers, Jeroen
Santi, Irene
Bonig, Halvard
Sandler, Andrew
Velthuis, Jurjen
Mielke, Stephan
author_sort Roy, Denis Claude
collection PubMed
description Overcoming graft-versus-host disease (GvHD) without increasing relapse and severe infections is a major challenge after allogeneic hematopoietic stem-cell transplantation (HSCT). ATIR101 is a haploidentical, naïve cell-enriched T-cell product, depleted of recipient-alloreactive T cells to minimize the risk of GvHD and provide graft-versus-infection and -leukemia activity. Safety and efficacy of ATIR101 administered after T-cell-depleted haploidentical HSCT (TCD-haplo + ATIR101) without posttransplant immunosuppressors were evaluated in a Phase 2, multicenter study of 23 patients with acute leukemia and compared with an observational cohort undergoing TCD-haplo alone (n = 35), matched unrelated donor (MUD; n = 64), mismatched unrelated donor (MMUD; n = 37), and umbilical cord blood (UCB; n = 22) HSCT. The primary endpoint, 6-month non-relapse mortality (NRM), was 13% with TCD-haplo + ATIR101. One year post HSCT, TCD-haplo + ATIR101 resulted in lower NRM versus TCD-haplo alone (P = 0.008). GvHD-free, relapse-free survival (GRFS) was higher with TCD-haplo + ATIR101 versus MMUD and UCB (both P < 0.03; 1-year rates: 56.5%, 27.0%, and 22.7%, respectively) and was not statistically different from MUD (1 year: 40.6%). ATIR101 grafts with high third-party reactivity were associated with fewer clinically relevant viral infections. Results suggest that haploidentical, selective donor-cell depletion may eliminate requirements for posttransplant immunosuppressors without increasing GvHD risk, with similar GRFS to MUD. Following these results, a randomized Phase 3 trial versus posttransplant cyclophosphamide had been initiated.
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spelling pubmed-73267072020-07-07 ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia Roy, Denis Claude Walker, Irwin Maertens, Johan Lewalle, Philippe Olavarria, Eduardo Selleslag, Dominik Lachance, Sylvie Buyse, Marc Wang, Kun Rovers, Jeroen Santi, Irene Bonig, Halvard Sandler, Andrew Velthuis, Jurjen Mielke, Stephan Leukemia Article Overcoming graft-versus-host disease (GvHD) without increasing relapse and severe infections is a major challenge after allogeneic hematopoietic stem-cell transplantation (HSCT). ATIR101 is a haploidentical, naïve cell-enriched T-cell product, depleted of recipient-alloreactive T cells to minimize the risk of GvHD and provide graft-versus-infection and -leukemia activity. Safety and efficacy of ATIR101 administered after T-cell-depleted haploidentical HSCT (TCD-haplo + ATIR101) without posttransplant immunosuppressors were evaluated in a Phase 2, multicenter study of 23 patients with acute leukemia and compared with an observational cohort undergoing TCD-haplo alone (n = 35), matched unrelated donor (MUD; n = 64), mismatched unrelated donor (MMUD; n = 37), and umbilical cord blood (UCB; n = 22) HSCT. The primary endpoint, 6-month non-relapse mortality (NRM), was 13% with TCD-haplo + ATIR101. One year post HSCT, TCD-haplo + ATIR101 resulted in lower NRM versus TCD-haplo alone (P = 0.008). GvHD-free, relapse-free survival (GRFS) was higher with TCD-haplo + ATIR101 versus MMUD and UCB (both P < 0.03; 1-year rates: 56.5%, 27.0%, and 22.7%, respectively) and was not statistically different from MUD (1 year: 40.6%). ATIR101 grafts with high third-party reactivity were associated with fewer clinically relevant viral infections. Results suggest that haploidentical, selective donor-cell depletion may eliminate requirements for posttransplant immunosuppressors without increasing GvHD risk, with similar GRFS to MUD. Following these results, a randomized Phase 3 trial versus posttransplant cyclophosphamide had been initiated. Nature Publishing Group UK 2020-02-11 2020 /pmc/articles/PMC7326707/ /pubmed/32047237 http://dx.doi.org/10.1038/s41375-020-0733-0 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Roy, Denis Claude
Walker, Irwin
Maertens, Johan
Lewalle, Philippe
Olavarria, Eduardo
Selleslag, Dominik
Lachance, Sylvie
Buyse, Marc
Wang, Kun
Rovers, Jeroen
Santi, Irene
Bonig, Halvard
Sandler, Andrew
Velthuis, Jurjen
Mielke, Stephan
ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia
title ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia
title_full ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia
title_fullStr ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia
title_full_unstemmed ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia
title_short ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia
title_sort atir101 administered after t-cell-depleted haploidentical hsct reduces nrm and improves overall survival in acute leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326707/
https://www.ncbi.nlm.nih.gov/pubmed/32047237
http://dx.doi.org/10.1038/s41375-020-0733-0
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