HDAC6 inhibition improves the efficacy BET antagonists. Inhibition of BET activity with JQ1 or BRD4 shRNA decreases c-MYC levels but also induces HDAC6 expression. Upregulation of HDAC6 has been associated with cancer progression and drug resistance and has been established as a potential anticancer target. Antagonizing HDAC6 with shRNA, the HDAC6 selective inhibitor ricolinostat, or the pan-HDAC inhibitor vorinostat blocks HDAC6 activity and augments the antimyeloma activity of BET inhibition.