Enrique M. Ocio, MD, PhD, from the University Hospital of Salamanca, Spain discusses optimizing the use of histone deacetylase inhibitors (HDACs) in the treatment of multiple myeloma (MM). HDACs were one of the original drugs with a novel mechanism of action to be approved for the treatment of multiple myeloma., However, clinical trials uncovered their toxicity in some patients. The patients that did benefit from panobinostat combined with dexamethasone and bortezomib saw an 8 month progression-free survival (PFS) benefit. Some approaches to achieve a reduced toxicity that can be employed are: optimization of the administration method, double or triple combinations of the HDAC inhibitor with other agents, and use of more specific HDACs such as ricolinostat, a HDAC6-specific inhibitor. Furthermore, for future drug development, it is necessary to investigate the mechanism of action of HDAC inhibitors and more importantly the immune effect of HDACs, which appears to be extremely beneficial in the maintenance phase. Data on patients who received the drug until progression, shows that they are disease-free for up to 5 years. Recorded at the 2017 World Congress on Controversies in Multiple Myeloma (COMy) in Paris, France.