Welcome to Managing Myeloma. I am Dr. Ajay Nooka. I am frequently asked, “What are the practical considerations in management of the most common adverse events with HDAC inhibitors?”
The next class of agents is the HDAC inhibitors. There is only one drug that is approved in this class, panobinostat, and this is a tough drug to give, but knowing how to give this drug is of extreme importance. Panobinostat is approved in combination with bortezomib and dexamethasone. The main side effects that you see with panobinostat are thrombocytopenia, fatigue, and diarrhea, and as you can recall from when we talked about bortezomib, it also comes with some GI toxicity. There is a significant overlapping toxicity for these agents. So, another proteasome inhibitor like carfilzomib shown by one of my colleagues, Dr. Kaufman as well as Jesus Berdeja, that it is a safe drug to be given in combination with carfilzomib. Now, the strategies that we employ to mitigate the toxicities are the schedule of giving panobinostat on days 1, 3, 5; that is the three doses in the first week. Then on days 8, 10, and 12, three doses in the second week in a 2-week cycle and a 4-week cycle. So, instead of giving it two consecutive weeks, if we can separate them as two alternative weeks, we certainly can mitigate the toxicities with the panobinostat. Knowing these toxicities certainly help with identifying them and help us to counter these toxicities.