Genomic and epigenomic predictors of response to guadecitabine in relapsed/refractory acute myelogenous leukemia.

ABSTRACT:

Background

Guadecitabine is a novel DNA methyltransferase (DNMT) inhibitor with improved pharmacokinetics and clinical activity in a subset of patients with relapsed/refractory acute myeloid leukemia (r/r AML), but identification of this subset remains difficult.

Methods

To search for biomarkers of response, we measured genome-wide DNA methylation, mutations of 54 genes, and expression of a panel of 7 genes in pre-treatment samples from 128 patients treated at therapeutic doses in a phase I/II study.

Results

Response rate to guadecitabine was 17% (2 complete remission (CR), 3 CR with incomplete blood count recovery (CRi), or CR with incomplete platelets recovery (CRp)) in the phase I component and 23% (14 CR, 9 CRi/CRp) in phase II. There were no strong mutation or me

SUBMITTER: Chung W 

PROVIDER: S-EPMC6647096 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature