Tazemetostat was effective in the treatment of the HSTL PDX model. (A) Immunoblotting showing on-target activity of tazemetostat, with a decrease in H3K27me3. Total histones were extracted from mouse spleen samples after 7 days of treatment. (B) Immunohistochemistry for H3K27Me3 in mouse spleen samples; original magnification ×400. (C) Bar graph showing spleen weights from mice in the PD cohort (treated for 7 days, n = 3 per group), and mice who were moribund at day 9 (n = 6) and day 11 (n = 2). (D) Kaplan-Meier curves showing overall survival of mice treated with vehicle (n = 9) or tazemetostat (n = 8). ***P = .0007 calculated using the log-rank test. ns, not significant.