MPN Care: How Can Molecular Testing Help?

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Topics include: What Are Myeloproliferative Neoplasms?

What can doctors anticipate from a person’s myeloproliferative neoplasm (MPN) by understanding their genetic subtype? How does mutational status impact treatment decisions? MPN expert Dr. Eytan Stein, from Memorial Sloan Kettering Cancer Center, joined Patient Power to discuss the value of genetic testing, common mutations seen in MPNs and how the results can influence care. Dr. Stein also gives updates on targeted therapies in development for MPNs. Watch now to find out more.

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Transcript

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Andrew Schorr:

Hello and welcome to Patient Power.  I'm Andrew Schorr.  Molecular testing and understanding what version of an MPN you have and what could it mean for therapy, either existing medicines or research.  Let's find out.  

Joining us is a researcher and a clinician, a hematologist?oncologist at Memorial Sloan Kettering, a myeloid specialist, and that's Dr. Eytan Stein. Dr. Stein, thanks for being with us.  

Dr. Stein:

Thank you so much for having me.  

Andrew Schorr:

Dr. Stein, so I am a myelofibrosis patient, and I learned that I have the, what is it, the V617F gene, a JAK2 V617F, and there's a medicine, ruxolitinib (Jakafi), that's been helpful for me over several years now.  Not everybody has that.  Not everybody continues to have that as a driver gene.  So where does molecular testing come in with having somebody with an MPN get the right therapy?   

Dr. Stein:

Yes, that's a really good question.  So when it comes to myeloproliferative neoplasms what's interesting about MPNs is that, as you said, there are a variety of genes that are—that can be mutated. The most commonly mutated genes in myeloproliferative neoplasms are the JAK2 gene, which you just mentioned. There's another mutation that can happen in patients called CALR, CALR mutation, and finally there's a mutation in the gene called, MPL or MPL.  

And what's interesting, in patients who have one of these mutations, especially if they have a disease like myelofibrosis, despite the fact that they don't all have mutations in JAK2, they still might respond to a JAK2 inhibitor, because what happens is that that pathway is activated even if you have some of these other mutations.  

The importance of molecular testing in myeloproliferative neoplasms I think is really two?fold. So, number one, it can affect—you can affect prognosis a little bit depending on what specific mutation you have. It can also help separate out what kind of myeloproliferative neoplasm you have.  You know, some patients will have myelofibrosis, some patients will have polycythemia vera, some patients, though, have like a little bit of an overlap between both of them, and it helps us sort out specifically what disease they have. 

And finally we're now doing a mutational testing on some other mutations, mutations in genes like ASXL1.  There are some other mutations we look at, and those can actually help us understand how does that additional mutation in addition to a mutation like Jack or CALR or CALR, how can the disease be—how is the disease modified by that additional mutation, meaning might we have to treat the patient a little bit earlier? Might we never need to treat the patient if they have another one of these mutations?  It can give us guidance for what their expected clinical course would be, and that can influence how often we follow up with the patient, how often we check in with them.  

Andrew Schorr:

Okay.  Now in some conditions these genes change over time, or what I guess you describe as the driver mutation, what's fueling your cancer.  So for someone like me, I've been living eight years with a diagnosis of myelofibrosis, or somebody who’s gone from PV to MF, is there sometimes an argument for retesting to see whether the genes have been changing or sort of rearranging, if you will?  

Dr. Stein:

I do—I mean, I do think there is an argument for doing that, but I don't do it at set time points.  What I do is I do it at the time of there's a clinical change.  So what that means is that if I see something in the patient's blood work that would suggest to me that maybe something is changing in the bone marrow, maybe the blood counts are going down a little bit more, maybe they're going up a little bit more, maybe the patient's spleen is getting a little bit larger, maybe the patient is not—now for whatever reason experiencing a little bit more fatigue, that prompts me to check again and to see if something has changed in the bone marrow.  

I think what we'd like to get to one day is to be able to do this testing before the patient has the symptom. Because if we could do the testing before the patient has the symptom and anticipate what's going to happen with a specific mutation that takes place or new mutations that might pop up, I mean, the goal would be to one day to get to a place where you could then find that new mutation, understand how long it would be until that new mutation causes a problem, and then treat that new mutation before it has a chance to cause clinical symptoms.  We're not quite there yet, but I think that's the goal of any therapy that we use for any disease.  

Andrew Schorr:

Okay.  So let's understand what's in the lab.  So he we've had a JAK2 inhibitor.  There are others that may be available soon, we'll see. They're working on antifibrotic medicines as well.  So how do you feel about sort of the pipeline of what's going on for this group of myeloid conditions, the MPNs?  

Dr. Stein:

Yeah.  So I think that the pipeline for all myeloid malignancies and specifically for MPNs is growing, and I think that's because we understand the biology of the disease better.  You mentioned that there are other JAK inhibitors that are in clinical development, which I think we're all very excited about.  There are antifibrotic agents.  One of the drugs I've actually been very impressed with, at least very early data is a class of drugs called bromodomain inhibitors or the other name is called BET inhibitors.   

There was actually an abstract presented at this year's ASCO meeting with a bromodomain inhibitor called CPI?0610, a drug from Constellation Pharmaceuticals, and they're not the only one that has a bromodomain inhibitor.  There are a lot of companies with bromodomain inhibitors, but this is the one that was presented.  

And what was really exciting about that, is that, you know, there are some patients with myelofibrosis who, their biggest issue is that they are anemic.  So you can control the symptoms of the disease and the spleen enlargement with ruxolitinib, but it's hard to get rid of the anemia.  What was interesting about this abstract—again very early, just a few patients—was that by giving this bromodomain inhibitor to these patients a number of the patients actually became transfusion independent and also had some spleen shrinkage. 

So there's a bigger study going on now to put more patients on the study, but I think that's very exciting because I struggle with what to do with these patients who have myelofibrosis and have persistent anemia, and I think that's one of the most exciting agents that I've seen that's coming out of the lab and that is in early?phase clinical studies.   

Andrew Schorr:

Okay.  So that's good news.  So we don't have uniform disease or symptoms or even progression, so in this age of what we hope is personalized medicine do you feel both with the molecular analysis and the drugs that are being developed we may have these more specific prescriptions, if you will, for patients given their situation?  

Dr. Stein:

I do.  I do think that's what's going to happen in the future, and that's why we hope to develop a medicine and a personalized medicine for every patient and every mutational subtype who has a myeloproliferative neoplasm.  

Andrew Schorr:

Okay. Well, I think it's important that we patients here, we want to be worked up appropriately and at the appropriate time so that our doctors, usually MPN specialists for these conditions, have the tools and the understanding of what our situation is at the time.   

I want to thank you, Dr. Eytan Stein, for your work in myeloid conditions and MPNs specifically, and thank you so much for being with us from Memorial Sloan Kettering today.  

Dr. Stein:

Okay. Thank you so much for having me. I really appreciate it.  

Andrew Schorr:

Andrew Schorr reminding you to find out your molecular situation with your doctor to you get what's right for you.  

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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Page last updated on August 20, 2019