Integrated clinical and genomic evaluation of guadecitabine (SGI-110) in peripheral T-cell lymphoma.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
23
11
2021
accepted:
04
04
2022
revised:
28
03
2022
pubmed:
24
4
2022
medline:
7
6
2022
entrez:
23
4
2022
Statut:
ppublish
Résumé
Peripheral T-cell lymphoma (PTCL) is a rare, heterogenous malignancy with dismal outcomes at relapse. Hypomethylating agents (HMA) have an emerging role in PTCL, supported by shared mutations with myelodysplasia (MDS). Response rates to azacitidine in PTCL of follicular helper cell origin are promising. Guadecitabine is a decitabine analogue with efficacy in MDS. In this phase II, single-arm trial, PTCL patients received guadecitabine on days 1-5 of 28-day cycles. Primary end points were overall response rate (ORR) and safety. Translational sub-studies included cell free plasma DNA sequencing and functional genomic screening using an epigenetically-targeted CRISPR/Cas9 library to identify response predictors. Among 20 predominantly relapsed/refractory patients, the ORR was 40% (10% complete responses). Most frequent grade 3-4 adverse events were neutropenia and thrombocytopenia. At 10 months median follow-up, median progression free survival (PFS) and overall survival (OS) were 2.9 and 10.4 months respectively. RHOA
Identifiants
pubmed: 35459873
doi: 10.1038/s41375-022-01571-8
pii: 10.1038/s41375-022-01571-8
pmc: PMC9162925
doi:
Substances chimiques
guadecitabine
2KT4YN1DP7
Decitabine
776B62CQ27
Azacitidine
M801H13NRU
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1654-1665Informations de copyright
© 2022. The Author(s).
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