Future Role for HDAC Inhibition in Multiple Myeloma

The role of the histone deacetylase (HDAC) inhibitor panobinostat in multiple myeloma will evolve over time, states Jatin J. Shah, MD. Panobinostat, which was approved in combination with bortezomib and dexamethasone by the FDA in February 2015, has also demonstrated efficacy when used in other combinations with a variety of other agents.

The PANORAMA-1 and PANORAMA-2 trials showed that panobinostat was effective in combination with bortezomib in relapsed/refractory disease. Panobinostat is also being evaluated in combination with lenalidomide and dexamethasone in newly diagnosed patients. Preliminary results showed a near doubling in complete response rates, he adds. Historically, improvements in the depth of response do translate to improvements in long-term outcome, says Shah.

Preclinical data show that HDAC inhibitors are synergistic with a range of drugs, including immunomodulatory drugs (IMiDs), states Andrew Spencer, MD. The combination of an HDAC inhibitor and an IMiD is tolerable and highly effective, he adds. More research is underway with HDAC inhibitors that will help determine the settings in which they are most effective.