ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia.
Adult
Female
Follow-Up Studies
Graft vs Host Disease
/ mortality
Hematopoietic Stem Cell Transplantation
/ mortality
Humans
Leukemia, Myeloid, Acute
/ mortality
Lymphocyte Depletion
/ mortality
Male
Middle Aged
Prognosis
Survival Rate
Transplantation Conditioning
Unrelated Donors
/ statistics & numerical data
Young Adult
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
23
08
2019
accepted:
29
01
2020
revised:
09
01
2020
pubmed:
13
2
2020
medline:
28
10
2020
entrez:
13
2
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32047237
doi: 10.1038/s41375-020-0733-0
pii: 10.1038/s41375-020-0733-0
pmc: PMC7326707
doi:
Types de publication
Clinical Trial, Phase II
Comparative Study
Journal Article
Multicenter Study
Observational Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1907-1923Références
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