OTX015 has in vitro and in vivo antitumor activity as a single agent in different lymphoma models, including ABC-DLBCL . Clinical responses including complete remissions with single agent OTX015 have been recently reported in patients with relapsed or refractory lymphoma or acute leukemia enrolled in phase I studies, in the absence of major toxicities [25, 26]. Although the mechanism of action of BET inhibitors is likely pleiotropic, down-regulation of genes involved in B cell identity and germinal center formation, and, especially in the ABC-DLBCL setting in which such effects can lead to apoptosis, inhibition of the B-cell receptor and nuclear factor kB signaling pathways play an important role [12–14]. Since OTX015 presented in vitro synergism when combined with different agents in lymphoma models , we evaluated the in vivo activity of OTX015-containing combinations in an ABC-DLCBL xenograft model.