A roundtable discussion, moderated by Ruben Mesa, MD, of the Atrium Health Wake Forest Baptist Comprehensive Cancer Center, focused on the latest updates in myeloproliferative neoplasms (MPN). Dr. Mesa was joined by Naveen Pemmaraju, MD, of the University of Texas MD Anderson Cancer Center; Sanam Loghavi, MD, of the MD Anderson Cancer Center; and Olatoyosi Odenike, MD, of the University of Chicago Medicine.
In the last segment of the roundtable series, the panel discusses the future of myelofibrosis (MF) treatment.
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Dr. Mesa: We’ve described Janus kinase (JAK) inhibitors for MF, which is a big step forward. However, we’re not where we want to be. We want to cause remissions and ideally cure patients. We’re in an era of new things coming, such as CALR antibodies and combination studies. What excites you the most?
Dr. Odenike: I am most excited about two phase III trials: the ruxolitinib and navitoclax randomized trial, and the ruxolitinib and pelabresib randomized trial. Both of those drugs and results were impactful, so I’m excited about the prospect that one or both drugs may be available. Then, we will be able to build upon that. Of the myriad of early phase trials that percolated, the CALR-directed therapies are the most exciting. I’m eager to see how those unfold.
Dr. Loghavi: With the role of inflammation becoming more prominent in myeloid malignancies, we can have studies where we comprehensively perform immune monitoring and immune profiling in these patients. The International Integrative Innovative Immunology for Myelodysplastic Syndromes (I4MDS) is trying to come up with a standardized immune profiling method for patients with MDS. I think we can do the same for MPN and potentially have targeted therapies to help these patients.
Dr. Pemmaraju: We’re entering into a golden era for MPN. The excitement is going to be moving beyond JAK. Next year, 2025, will be the 20th anniversary of the elucidation of JAK2 V617F. That’s been the backbone and starter of our field. We have this tripartite excitement—first, the combination agents Bcl-XL and bromodomain extraterminal (BET) inhibitor being the furthest to develop, but there are others coming such as ZPO1 and MDM2 inhibitors. The second is standalone novel agents such as the telomerase inhibitor, Bcl-XL, BET, or CD123. I think that’s super exciting to not only do in the relapsed setting, but eventually move it up into the frontline setting.
Finally, the mutant-specific era has now begun. CALR-directed therapy is exciting, whether it’s vaccines, monoclonal antibodies, or bispecifics. Then there’s mutant JAK2 and type II JAK inhibition, so trying to hit the JAK2 mutation in a more specific way than we’ve done before. All of that is in phase I or higher clinical trials, so we’ll see what happens.
Dr. Mesa: I’m excited by the depth and breadth of a team that’s trying to contribute to this. Discovery scientists are trying to understand the dynamics of the clonal neoplasm and how that’s evolving. We have people trying to take a deep dive into next-generation JAK inhibition, CALR-targeted therapies, and candidate biomarkers of progression. Although it’s not a common disease, it’s heterogeneous. Any uniform approach is not likely to be beneficial. The more tools we have to match with patients, the better off we are.