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New Studies on Risk Factors for MPN Progression

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Published on August 2, 2021

Are There Modifiable Risk Factors for MPN Progression?

Are there modifiable risk factors that can lower the risk of MPN progression? In this Ask the Expert program, Naveen Pemmaraju, MD, of the MD Anderson Cancer Center, discusses several studies around the world that are examining if comprehensive molecular mutation panels can be used to make predictions about the chance of progression.

Support for this series has been provided by Bristol Myers-Squibb. Patient Power maintains complete editorial control and is solely responsible for program content.


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Transcript | New Studies on Risk Factors for MPN Progression

What Are the Risks for MPN Progression? Are There Modifiable Risk Factors That Patients Should Consider?

Dr. Pemmaraju: One of the most important areas of research for me personally and my colleagues in the MPN world are thinking about, “What are the risk factors for progression of the disease?” To either what we call a more accelerated phase of a MPN or myelofibrosis, or blast phase, which essentially is AML, acute myeloid leukemia. Unfortunately, in 2021, as we come out of the pandemic, there aren't a whole lot of breakthroughs in terms of therapeutics, in terms of treating, but we have had some laboratory breakthroughs and others. And basically, what I mean by that is we're starting to try to predict who are those patients who have a chronic MPN – PV, ET, myelofibrosis — and then suddenly they take off into a more accelerated or blast phase leukemia phase.

And a lot of studies across the world, from Europe, from Asia, from the States, other places, are starting to show that a comprehensive molecular mutation panel. So going outside of the big three genetic drivers that we know about – JAK2, CALR, and MPL – and now focusing on more than several dozen other genetic factors, which are not always commonly tested. Maybe the occurrence of those can predict that someone's going to progress sooner. And some examples of those are starting to come out in multiple datasets. So ASXL1, EZH2, IDH1 and 2, SRSF2, so on and so forth. It's a real alphabet soup of letters and numbers, but basically these are genes that are mutated. Most people are not born with them. They acquire them over time. And importantly, you can pick up or acquire these mutations over the course of your MPN. That's a big finding. So, can we identify those mutations? Can we now check them either at diagnosis or as you go through your course of your disease? And then “Aha,” you have acquired X, Y, Z mutations.

What Are We Learning From New Studies and Clinical Trials?

Now the second part of that is, is there anything we can do about it? So that's where all the active clinical trials are, some dedicated to accelerated phase and blast phase. Some trying to pick up on these individual mutations that may be targetable, meaning that there is a drug that's already there, for example, clinical trials with the IDH1 and 2 mutations, because there are oral targeted therapies for those. And then still a third area is combination therapies, taking either the JAK inhibitor that you're already on, adding on a new drug, or a completely novel approach.

Finally, really the only curative modality that we still know about in these dreaded disorders once they become accelerated or blast phase is the allogeneic stem cell transplant, which of course does not apply to many patients in terms of availability and accessibility. So, I think there's a lot of hope here. There's a lot of clues and directions, but this will be one of the most important areas in the next five to 10 years for our collective research together.

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