In vitro and in vivo antimyeloma activity of I-BET 762. (A) Day 1 and 2 OPM-2 myeloma cell line proliferation in response to different concentrations of I-BET762, I-BET151, and JQ1 as assessed in ³H-thymidine incorporation assays. I-BET762 is also compared against the inactive I-BET768 compound. Y-axis depicts normalized proliferation (n = 3). Data are shown as mean ± SEM. (B) Body weight of mice treated with different dosing schemes of I-BET762 or vehicle control. Day 1 corresponds to day 15 (ie, when I-BET762 administration commenced). Data are expressed as mean ± SEM (n = 15) for the start of each dosing schedule. (C) Peripheral blood hLC concentration at time points shown in mice treated with 4 different dosing schemes of I-BET762 (3 mg/kg per day, 10 mg/kg per day, 30 mg/kg once every other day [ie, alternate days], and 30 to 20 mg/kg per day [ie, 30 mg/kg for 15 days, followed by 2 weeks off treatment, followed by 20 mg/kg until termination of the experiment starting from day 15 after myeloma cell inoculation] or vehicle control (n = 8 to 11 mice per dosing schedule). Samples from one animal treated with vehicle and one animal treated with 20 to 30 mg/kg were taken at days 54 and 62, respectively, but presented in the day 58 group. Data are shown as mean ± SEM. *P < .05; **P < .01; ***P < .001. (D) Frequency of hCD38⁺ OPM-2 human myeloma cells in the BM taken from the femur as assessed by flow cytometry at the time of euthanasia. Data are shown as mean ± SEM (n = 11 to 15). (E) Kaplan-Meier survival analysis of OPM-2–bearing mice in different treatment groups (n = 8 to 11 mice per dosing schedule) for each of the I-BET762 treatment groups against vehicle-treated group; log-rank test P ≤ .002. nd, not done.