Unmet Needs and Future Directions in Treating MPNs

Transcript:Harry P. Erba, MD, PhD: This has been extremely informative. Before we end this discussion, I’d like to open up the floor and ask each of you to provide some final thoughts on unmet needs in these 2 diseases. Why don’t we start down here with Ruben?

Ruben A. Mesa, MD, FACP: I think we’ve made tremendous progress. The key unmet need I would highlight is understanding the issue of progression. Why do patients progress? How do we monitor it? This is crucial. What is the driver of progression in P vera [polycythemia vera]? How do we impact that? How do the therapies that we have—I think they do have an impact on progression, but we don’t have a good way of monitoring it. How do we optimize that? Should we use ruxolitinib earlier in P vera because it’s helping to avoid progression? I don’t think we can answer that. Should we use it in everyone with myelofibrosis, even very early on, because it’s helping to avoid progression? How do we avoid the acute leukemia phase of the disease, which is the most fatal? I think if we understand progression, we will be able to better use the therapies that we have, and we’ll be able to better design therapies to further impact the disease.

Harry P. Erba, MD, PhD: Very good. Mary Frances?

Mary Frances McMullin, MD, FRCP, FRCPath: We’ve come a long way and we have lots of therapies, but we still go back to the points of how we actually cure or eliminate these diseases. That still has to be the unmet need. We’ve talked about JAK2 inhibition. Are we going to have CALR mutation inhibitors in the future, etc? The overall picture remains the same as an unmet need. Then the immediate unmet need is definitely in myelofibrosis [MF], where we’re seeing all the patients who have had a good response to therapy but are now losing it. Where do we go from here? Which of these agents is going to be of use?

Harry P. Erba, MD, PhD: There have been some very interesting preclinical studies, including the last 1 at the plenary session at ASH [American Society of Hematology Annual Meeting & Exposition] looking at the pathogenesis of MPNs [myeloproliferative neoplasms] driven by CALR, which leads to hypotheses of how we might be able to intervene in that group of patients. Jamile?

Jamile M. Shammo, MD, FASCP, FACP: For PV [polycythemia vera], the issue there is a lack of appreciation of the symptomatology that patients have. We have to do a better job at appreciating this, and perhaps attending to it. Of course, understanding progression and what governs that, and the impact of next-gen [next-generation] sequencing is, perhaps, in these practices, also important. For MF, taking care of patients who have significant cytopenias that might compromise treatment, even with such an effective JAK2 inhibitor therapy that we have available, is key.

Harry P. Erba, MD, PhD: Rami, last word. Make it good.

Rami Komrokji, MD: Again, I think it’s an exciting time. We’ve definitely made a lot of progress. We have more options to offer our patients. I think we always try for medications that will alter the natural history of a disease and improve survival and quality of life. That’s always going to be an unmet need, in a general view.

In myelofibrosis, I see the ruxolitinib failure group as a challenging group. That’s an unmet need. We definitely need some new therapies for those patients. Patients that have cytopenias in myelofibrosis are another challenging group of unmet need.

In polycythemia vera, I agree. I think we don’t pay much attention to symptoms and management of symptoms. As Ruben even mentioned, there is still a tendency to change to the newer treatments in those patients. There is an education opportunity there, and unmet needs for second-line treatments for those patients. Educate the doctors to use those medications. Again, it’s an exciting time. We’ve learned a lot, and the outlook should be positive.

Harry P. Erba, MD, PhD: Agreed. Thank you all for your contributions to this discussion. On behalf of our panel, we thank you for joining us. We hope you found this Peer Exchange discussion to be useful and informative.

Transcript Edited for Clarity