DNA methylation change in peripheral blood of the 5 PTCL patients treated in the expansion cohort. (Ai) Absolute and (Aii) percentage change in GDMS values compared with cycle 1, day 1. All 3 patients with AITL, including 1 with no appreciable demethylation, responded, 1 patient with extranodal natural killer/T cell lymphoma with profound demethylation responded, and 1 patient with enteropathy-associated intestinal T-cell lymphoma with nearly 40% reduction in GDMS had progression of disease. (B) Time course of global blood DNA methylation changes compared with day 1 of cycle 1 across all chromosomes after treatment; only sites with an absolute log-fold change >1 are shown. Methylation values are color coded such that red indicates lower methylation and blue higher methylation. (C) Heatmap of significantly differentially methylated CpG sites from day 1 of cycle 1 to day 1 of cycle 2. The leftmost column indicates significantly demethylated CpG site on day 22 (pink), and on days 15 and 22 (light blue) at values below a false discovery rate of 5%. The top row indicates patient histology. Methylation values scaled by CpG site are color coded such that red indicates lower methylation and blue higher methylation. ENKTL, extranodal NK/T-cell lymphoma; EATL, enteropathy-associated T-cell lymphoma.