(A) NSG mice (n = 8 per treatment group) bearing TMD-8 (MyD88 mutant) and Ri-1 (MyD88 WT) tumors were treated i.p. daily with either vehicle, panobinostat (5 mg/kg), ibrutinib (2mg/kg), or the 2 drugs together, 5 times weekly. Tumor volumes were measured 3 times per week. Differences between groups were calculated with the ANOVA with Dunnett’s test. **P < 0.005. (B) NSG mice (n = 11 and 8 per treatment group, in TMD-8 and Ri-1 experiment, respectively) were treated i.p. daily with either vehicle, panobinostat (5 mg/kg), ibrutinib (2mg/kg), or the 2 drugs together, 5 times weekly for 3 weeks and observed until death after the end of the treatment. Differences between groups were calculated with ANOVA with Dunnett’s test. ***P < 0.0005. (C) Kaplan-Meier plot of the percent survival as a function of time from last drug administration. Data are from n = 11 and 8 for all groups in TMD8 and Ri-1 tumors, respectively. ****P < 0.0001.