Analogous to the vast majority of human tumors and independent of their cell of origin, DLBCL cells also bear recurrent somatic mutations in genes coding for proteins involved in chromatin structure and remodeling that cause profound changes at the epigenetic level [3, 7]. Of clinical relevance, epigenetic changes can be at least partially reversed and epigenetic drugs can increase sensitivity to other anticancer agents [7–10]. Over the last few years, inhibitors of the bromodomain and extraterminal (BET) protein family have become the focus of extensive research as a novel class of epigenetic drugs . BET proteins are key epigenetic regulators of gene transcription and their inhibition has resulted in antitumor activity in different tumor models, including lymphomas [11–20]. OTX015 (MK-8628) is a thienotriazolodiazepine compound that potently inhibits the BET proteins BRD2, BRD3 and BRD4 . The compound competitively occupies the acetyl-binding pockets of BET bromodomains, leading to release of the BET protein from the chromatin . Importantly, in normal and cancer cells, more than half of all BRD4 proteins are bound to a small number of enhancers (super-enhancers) that control the expression of genes fundamental to the control and establishment of individual cell identities, such as PAX5, BCL6, CD79A, CD79B, FOXO1 in B-cells or PRDM1, IRF4 and MUM1 in plasma cells [22–24].