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What Are the Phases of MPN Progression?

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Published on April 20, 2021

Doctor Explains Progression in MPNs

What are the phases of MPN progression? Keep watching to hear Dr. Ruben Mesa, MD, Director of the Mays Cancer Center at UT Health in San Antonio, explain the differences between each phase of myeloproliferative neoplasms and the likelihood of progression. Dr. Mesa also gives an update on MPN research and clinical trials that are currently underway.

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Transcript | What Are the Phases of MPN Progression?

Dr. Mesa: Hello. My name is Ruben Mesa, and I'm the Executive Director of the Mays Cancer Center at UT Health, San Antonio. The concept of progression in MPNs is a very important one, and understandably, one that causes great distress for MPN patients. For most individuals diagnosed with an MPN, it is progression that makes the disease the most threatening to them. Think of MPNs as potentially having three different phases.

What Are the Three Phases of MPN Progression?

One phase is that of ET or PV, essential thrombocythemia or polycythemia vera. This level of disease overlaps between itself to a great degree. There can be risk of blood clots. There might be symptoms. There sometimes can be enlargement of the spleen, but overall, this is a phase of the disease where we control the disease and the majority of individuals, if they remain in that phase, will live out the rest of their normal lives. So, this is kind of the first phase.

Now, it is unclear why individuals progress from one phase to the next and most surely not everyone progresses. In fact, the majority of ET and PV patients will not progress. Age is a factor. The longer one has the disease, particularly over 10 years, the greater the likelihood of progression, but it's never a certainty.

The second level is myelofibrosis. Whether that's primary myelofibrosis, so some patients start there, or individuals who progressed from ET or PV into post-ET or post-PV myelofibrosis. At this phase of the disease, there can be enlargement of the spleen. There tends to be additional symptoms: weight loss, night sweats, bone pain, fevers. There can be low blood counts and there can be a variable risk of moving on to acute leukemia. Myelofibrosis can be life-threatening for some individuals, although not all. The way the disease affects people is quite heterogeneous and how we approach it is very much on an individualized and risk-based format.

The third potential level, the one that fortunately the very fewest MPN patients reach, is that of acute leukemia. Not everyone with myelofibrosis progresses to acute leukemia. In fact, well, less than half. Why acute leukemia is the most severe phase, is that in that phase of the disease, the blood counts can be very low and there can be very severe risks of blood clots or bleeding. And acute leukemia frequently is a very life-threatening change. Why do people progress? We don't fully know, but there is a lot of research trying to better understand why people progress and for us to better try to track that and develop therapies to avoid progression.

What Is on the Treatment Horizon for Essential Thrombocythemia and Polycythemia Vera?

For essential thrombocythemia and polycythemia vera, I'm very excited about a couple of different things. We realize that there's a tremendous pipeline of new therapies being developed for myelofibrosis. As those move forward, some of those will undoubtedly impact PV and ET. But in the much more short term, one, there's the important trials and likely soon availability of ropegylated interferon alfa-2b (Besremi), or “ropeg,” as we frequently call it for PV and ET. In PV, it's been approved in Europe and has been shown to be as effective, if not more so, than hydroxyurea (Hydrea) for controlling blood counts, helping decrease the JAK2 allele burden, potentially having a disease-modifying capability. There are many patients on long-acting interferons. Many of this has been in off-label use of other products.

So this might be an important step forward and important option that is also honoring NCCN guidelines. In parallel with that, Dr. Verstovsek and I are leading a global study looking at that same agent as second-line for patients with essential thrombocythemia. And that trial is ongoing and accruing, and we think that therapy will be beneficial.

Second, there's a novel approach of trying to use hepcidin mimetics, such as PTG-300 from Protagonist to make patients with PV phlebotomy independent, potentially have more stable control of the hematocrit, improved symptoms. That might really change our treatment paradigm for lower-risk patients. Finally, there are new therapies in development, such as MDM2 inhibitors and the LSD1 inhibitor from Imago in ET patients in the second-line setting. And we have a trial ongoing with that as well. So although much activity in myelofibrosis, there are things to be excited about for ET and PV. And I do think ropegylated interferon will really change our treatment approaches.