Transcript:Cem Akin, MD: Future treatment options focus largely on new kinase inhibitors with activity against the KIT D816V mutation. In addition to midostaurin, which is a nonspecific KIT inhibitor, there are at least 2 other specific KIT D816V inhibitors that are in early stage clinical trials—one made by Blueprint Medicines and the other by Deciphera. There may be more that I’m not aware of at this point. It would be interesting to see the results from the clinical trials using those kinase inhibitors, given the success of midostaurin in the phase II trial. I personally would have positive expectations from those trials, but we have to wait and see what they show.

There are also trials using other inhibitors, such as ibrutinib, targeting other molecules. One is a small trial in Stanford led by Dr. Jason Gotlib. There are also small trials targeting surface markers of abnormal mast cells. As an example, interleukin-3 receptor, or CD123, is targeted in one trial. CD30, which is not expressed on normal mast cells but is expressed on abnormal mastocytosis mast cells, is the target in another trial. So, we have to, again, wait and see whether those trials would produce favorable responses or not.

Another important area is that we had to consider the fact that not one single drug will give us all of the benefits. We may have to combine some of these drugs together to achieve the most benefit. So, it may be that in the future, we might end up combining a kinase inhibitor with Cladribine—2 different drugs with 2 different mechanisms of action—or maybe a drug targeting a surface receptor plus a kinase inhibitor. Or maybe we’ll investigate the role of these new drugs in conditioning regimens in stem cell transplantation. We know that conditioning regimens are important. Myeloablative regimens tend to work better in producing more overall survival and progression-free survival than nonmyeloablative regimens. So, I think we may have to be creative and incorporate some of these newer treatments into the conditioning regimens to see what the optimal outcome for these patients are.

And finally, there’s the other side of the spectrum where patients with benign disease don’t necessarily have a hematologic problem or decreased life expectancy because of mastocytosis. But there’s also a huge unmet need for that population as well because they are suffering from—some of those patients, not everybody—the symptoms of mast cell mediator release and mast cell activation symptoms, such as flushing, abdominal symptoms, and hypotension. And some of these drugs, if they turn out to have a very favorable toxicity profile, may also be tried in those benign forms of indolent mastocytosis.

Transcript Edited for Clarity