Unmet Needs in Myelofibrosis

Transcript:Daniel J. DeAngelo, MD, PhD: For patients with chronic myelofibrosis, the big issue is, how do you reverse the fibrosis? JAK inhibition has been shown on anecdotal cases to reduce the fibrosis. But, in both the COMFORT-I and COMFORT-II studies, there were a limited number of paired samples in long-term treatment samples showing reduction in fibrosis. And it was hard to associate the reduction of fibrosis in those isolated cases with response outcomes. So, that’s clearly an unmet need. Can you reverse the fibrosis with oral therapy, or therapy in general, different from transplantation? We know that stem cell transplantation is able to reduce and reverse the fibrosis. Can you achieve that same reduction with other targeted therapies? And so, right now, I would say that that’s the number one unmet need in terms of treatment for patients with chronic myelofibrosis.

Kim-Hien T. Dao, DO, PhD: I think we still need some new therapies in this area. I think ruxolitinib has really helped in symptom management and spleen volume reduction. However, we’re all hoping that new therapies and combination therapies will alter the natural history of myelofibrosis. And, I think there’s some exciting things going on right now in terms of combining ruxolitinib with interferon and other agents that might actually change the degree of fibrosis more substantially, and also improve marrow function. Then, of course, it would be great to see that it changes the natural history in terms of reducing the mortality associated with myelofibrosis, but also reducing the risk for acute myeloid leukemia, myeloid dysplasia, and progressive disease in myelofibrosis. Some of the newer agents that we’re very excited about are in clinical phase II trial studies right now. There’s the telomerase inhibitor, imetelstat, and also PRM-151, which is a recombinant protein that will reduce the fibrosis. Preliminary data suggests that it improves anemia and also reverses the fibrosis within weeks to months of therapy.

The other unmet need that we need to do better on is basically allogeneic stem cell transplant. Right now, the outcome ranges for long-term survival are anywhere from 30% to 50%, depending on risk characteristics and also patient characteristics. And, I think, with better supportive care, better matching, and also potentially posttransplant maintenance therapy, we might do better in that outcome.

Transcript Edited for Clarity

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