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Hope and Progress in MPN Treatment: Updates From an Expert

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Published on May 15, 2018

On location at the University of Colorado Anschutz Medical Campus, Dr. Brandon McMahon shares an update on the progress being made in the treatment landscape for myeloproliferative neoplasms (MPNs). He discusses the evolving science in genetic testing and how prognostication is being improved. This interview provides a hopeful overview and outlook into the world of MPNs.

Produced in Partnership with the University of Colorado Anschutz Medical Campus. Sponsored by Incyte Corporation.

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Transcript | Hope and Progress in MPN Treatment: Updates From an Expert

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.

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.  We're actually on location in Aurora, Colorado, at the CU Anschutz medical campus, and with me is one of the leading hematologists here, Dr. Brandon McMahon. Thank you so much for being with us. 

Dr. McMahon:

Thank you, Andrew.  Thank you for having me.   

Andrew Schorr:

Well, you're an MPN specialist… 

Dr. McMahon:

Correct, yep. 

Andrew Schorr:

…so people come far and wide to see you or referred to you by community oncology clinics, and I think the first question I want to ask you is knowing where research is headed, and you've been in this field for a while, are you hopeful for those of us living with an MPN?  

Dr. McMahon:

I'm very hopeful. I'm very hopeful.  I think that with this disease and getting—being able to identify the JAK2 mutation and then later on the CALR mutation and the MPL mutation I think that we're in an era where we're going to be able to get to better targeted therapies to treat these diseases.  

Andrew Schorr:

Okay.  So we've had some medicines that have been around for a while, including people—some people take baby aspirin—and then we have also approved in myelofibrosis and PV, maybe being considered for ET, ruxolitinib or Jakafi, and there are other medicines in the pipeline. Give us a window into what's in development and what a difference it can make.   

Dr. McMahon:

There's a—boy, there's a huge list of things that are in development right now.  There's re-evaluation of medications that have been around for a long time like, for example, interferon.  There are ongoing studies looking to see if that does make a difference and if it is disease?modifying in certain circumstances.  

There are newer medications like the telomerase inhibitor like imetelstat.  There are new JAK inhibitors, JAK1 inhibitors, JAK2 inhibitors, like pacritinib and itacitinib.  The list goes on.  There are a lot of medications in development right now, both on their own and in combination with ruxolitinib and other standards of care.   

Andrew Schorr:

Okay.  So as this develops, then, it gets more complicated for you, doesn't it…

Dr. McMahon:

It does.  

Andrew Schorr:

…to see what can work with what for which patients.  

Dr. McMahon:

Right. Exactly.  And that's actually some of the—which makes it very exciting and very rewarding to go in and work with patients and their families to try to figure out which drug is going to be best for them or which intervention is going to be best for them, give the most benefit with the least amount of toxicity. 

Andrew Schorr:

Okay.  So you have medical science continuing to develop. So take for me, living with myelofibrosis now six years or so, and other people with ET and PV, is this a constant discussion we're having is where are you in your MPN journey, what do we have now either approved or in trials, and how could this even be a bridge to what's next? 

Dr. McMahon:

Right. That's a very, very good point.  I mean things are changing rapidly.  The knowledge we have about what causes the disease or additional things that add to sort of the phenotype or how the disease manifests in each individual person is changing so rapidly, and that's leading to more discoveries with regards to interventions.  So what we do now today in 2018 may be different in a year from now or five years from now which, again, makes it very exciting.   

Andrew Schorr:

Okay.  So there are side effects of medicines, and there are symptoms that go along with the diseases.  How do you feel about being able to manage those now if we have an active dialogue with you on what's going on?  

Dr. McMahon:

It's a lot easier.  And one big thing, that last statement you said is a huge, huge part of it, for patients to bring up what kind of symptoms they're having.  I think sometimes patients are worried about bringing up things that have been problematic for them, because they don't—they're not sure if there's going to be anything that could be offered. Or they don't want their family members to know that they've been living with certain kinds of symptoms, pain, depression or those kind of things.  So the first thing, I always strongly encourage people to be very open so that we can at least address what's going on.   

The other big thing is that people may be having symptoms that they think are attributed to the MPN or for that matter the treatment of the MPN and maybe it's not at all. It may be—it's important to obviously address those things, but maybe there's something else that's going on that's not being looked at or not being addressed.  People still get other complications, infections or cardiac issues that may be separate from the disease, so it's very important to keep those symptoms and things that they're worried about open with their providers. 

And then we have a lot more—we have a lot more treatments that are available even for—maybe not specific to the disease itself but supportive medications that can be very helpful for the treatment of side effects or for that matter for the underlying disease.  

Andrew Schorr:

Okay. Related to medical science moving forward, it is moving forward in the MPNs, but it's moving forward in other conditions as well, and we cancer patients hear about that and wonder, does it apply?

Dr. McMahon:

I know.  

Andrew Schorr:

For instance, do the medicines that have made a difference in lung cancer make a difference in MPNs?  Are the medicines like this CAR?T therapy, chimeric antigen receptor therapy, that are helping some people with certain aggressive lymphomas or acute leukemias, does that apply here?  How do we sort that out, because—or is it hype or is it just not known yet?  

Dr. McMahon:

Right.  And I think that it's the latter that is pretty much the truth is that these—a lot of these newer developments are specific to diseases in particular patient populations in that disease that may not be applicable to even someone else with the same disease.  So if it's been used in lymphoma, CAR?T in lymphoma, another person who has lymphoma, it may not be applicable to that person, so you always have to take that with a grain of salt.   

It's important to stay up on the news, but it's also important to discuss with your provider, because they may say, well, actually, it's not really relevant in your particular case.   

Andrew Schorr:

I want to ask you about progression?  So people with ET worry, will it progress to PV?  If you have PV, will it progress to myelofibrosis?  If you have myelofibrosis, will it progress to acute leukemia?  

Dr. McMahon:

Mm?hmm, right. 

Andrew Schorr:

So what do we know now about sort of I guess you'd call it prognostic factors?   

Dr. McMahon:

In terms of…

Andrew Schorr:

Progression. 

Dr. McMahon:

So progression. So I mean the prognostic factors again, that's another kind of moving target as we're learning more about the diseases.  We do know that there are patient?specific characteristics that can help prognosticate. Those are things like do they have constitutional symptoms, do they—are they anemic?  Is their platelet count low, or is their platelet count high. Have they had a blood clot, in the case of PV and ET?  

But then there are also disease?specific characteristics that also change too—so if they have certain genetic abnormalities that they have.  And those are a little bit more of a moving target, because you may not have a certain mutation at day two of your disease, but it may change down the road.  

And actually that part of the puzzle may make a big difference with regards to treatment options.  We're learning that, for example, like I mentioned imetelstat, which is a telomerase inhibitor that is in development right now, we know that patients who are JAK2 negative and ASXL1 positive, they don't respond to that drug.  So getting that piece of information is going to be very important to really individualize treatments, not only that but also for the prognostic factors too.   

Andrew Schorr:

So the testing that you can do now, the genomic testing, if you will, is pretty important, isn't it, for an MPN patient?   

Dr. McMahon:

It is.  It is, yeah.  There's a—not only just the driving mutations, so patients who have MF calreticulin type 1 mutation, they're going to do a lot better than patients who are triple negative, they don't have any of the driving mutations detected.  

And then on top of that there are other mutations I mentioned, like ASXL1.  There are other ones.  There are spliceasomes and epigenetic modifiers, all these different kinds of genetic factors that can really influence prognostication, and again, as I mentioned earlier, also potentially how the person may be treated. 

Andrew Schorr:

So it would seem fair with these rare conditions, pretty rare conditions we're talking about, that people should first of all advocate that they get today's testing, if you will, that can be pretty sophisticated and maybe have a consultation with someone like you to see what does it mean for me?

Dr. McMahon:

Right.  I totally agree with you.  And I always encourage people to get another opinion just to see if there's anything else that could be offered or if there's anything else, either from a diagnostic standpoint or from a therapeutic standpoint. 

Andrew Schorr:

And related to these genomic changes, do they change over time?  So in other words, if I am seen with certain cancer genes early in my journey, might they change later, and therefore the treatment should change based on that?   

Dr. McMahon:

Absolutely. And again with some of these other genetic factors, the nondriving mutations, not JAK2, CALR or MPL and MPN, the other ones, if they—if you don't have certain of them at one point in your disease and you develop them that may tip the scale if you have MF and you say, gosh, you're 68 years old and you didn't have this sort of bad?acting gene before but now you do, that may point us or push us more towards exploring the transplant option.   

But, on the other hand, if you—if the patient is doing well and they don't have these mutations you may say, gosh, you may do just fine on the treatment you're on now, and we'll just re-evaluate in a short period of time.  

Andrew Schorr:

One last question.  Cancer is wily and can get smart about certain medications, and some other cancers we have the issue of resistance where your cancer becomes resistant to a treatment that may have been working for you for a while.  Do we have a concern about resistance with Jakafi, for example, or other medicines that may be used?  

Dr. McMahon:

Yeah, I think—the short answer is yes.  For example, with ruxolitinib we know that about half of the patients with myelofibrosis who are on ruxolitinib will stop the medication after about three years. So some of it is because of resistance, some of it's because of intolerance, some of it's because of disease progression, but it's not—it's certainly not—there's certainly room for improvement, let's put it that way.  

Andrew Schorr:

Okay.  So that's why we need new medicines.  

Dr. McMahon:

Exactly, and that's why we encourage people to go on clinical trials as much as possible.   

Andrew Schorr:

Okay.  Well, I know you're a researcher as well as a clinician.  I want to thank you for what you're doing here in Colorado.  And thanks for being positive…

Dr. McMahon:

Yeah.  Of course.  

Andrew Schorr:

…because it means a lot to us.  Thank you so much.  

Dr. McMahon:

Yeah, of course. Thank you, Andrew, I appreciate it. 

Andrew Schorr:

Yeah, so here we are with Dr. McMahon in Colorado and major research going on around the world.  And these folks, we're so fortunate in the MPN community, work together for the benefit of us.   

On location in Aurora, Colorado, I'm Andrew Schorr.  Remember, knowledge can be the best medicine of all.  

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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