Andrew Spencer discusses the role ofhistone deacetylase (HDAC) inhibition in multiple myeloma and what we need to understand better to explore the further potential of HDAC inhibition.
FILMED AT THE EUROPEAN HEMATOLOGY ASSOCIATION (EHA) ANNUAL MEETING, JUNE 2016
WHY IS HISTONE DEACETYLASE (HDAC) INHIBITION IMPORTANT IN MULTIPLE MYELOMA (MM)?
00:12 – I think HDAC inhibition is important because there’s still no curative option in myeloma, so we need to continue to explore alternative strategies. And there’s a very powerful rationale for this inhibition in myeloma that’s been demonstrated by pre-clinical work, and clinical trials so far have shown that you can re-sensitise resistant disease with the use of these drugs. So outcomes in patients with very few therapeutic options are going to be increased.
HOW MIGHT HDAC INHIBITORS FIT INTO THE THERAPEUTIC ARMAMENTARIUM FOR MM?
00:56 – Well the evidence for HDAC inhibitors so far has been in patients with multiple relapse disease. But I think because of the fact that they’re generally oral agents and probably at multiple mechanisms of action, we need to explore them in earlier phase disease and perhaps in entities like smouldering multiple myeloma, although we may have the ability to change the natural history of the progression to symptomatic myeloma by using these agents earlier.
WHAT DO WE NEED TO UNDERSTAND BETTER TO EXPLORE FURTHER THE POTENTIAL OF HDAC INHIBITION IN MM?
01:36 – I think to use the agents optimally we need to understand better their mode of action. There are various theories about how they work and there’s various levels of evidence for some of those theories. But I think what happens when we use them clinically is still very unclear and there’s certainly evidence that there could be direct anti-tumour action. But also, it’s highly likely that they’ve got an immunomodulatory capacity, which will be very important for long-term disease control and perhaps for combination approaches with other immuno-oncology agents.