ASCO 2015: Discussing Polycythemia Vera Updates with a Roundtable of Experts

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Topics include: Treatments

As part of our coverage from the 2015 annual meeting of the American Society of Clinical Oncology (ASCO), Patient Power assembled a roundtable discussion with MPN experts, Dr. Ruben Mesa, Dr. Alison Moliterno, Dr. Naveen Pemmaraju and patient advocate Heidi Cascarano to discuss the latest news in polycythemia vera (PV), one of the myeloproliferative neoplasms (MPN).  The experts discussed the recent approval of ruxolitinib (Jakafi®) to treat polycythemia vera and the updated data surrounding this approval, as well as the risk stratification of patients with PV over time. The experts shared their perspective on what we have learned about the disease since the discovery of the JAK2 mutation 10 years ago, including the varied age range of patients and the difference in presentation and symptom burden in male and female patients. While there are treatments that currently modify and reduce symptoms of PV, the experts talk about the desire to focus efforts on eradicating the disease in the future by identifying therapies to address the mutations at the stem cell level. Also discussed are new therapies in development such as histone deacetylase inhibitors and MDM2 inhibitors as well as combination therapies using older drugs such as interferon with newer drugs to better treat the disease. Heidi Cascarano provided a patient perspective, expressing her hope for the future of treatment and why it’s so important to see a specialist and to advocate for yourself.

Sponsored though an educational grant from Incyte Corporation.

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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. 

Dr. Mesa:

Hello.  My name is Ruben Mesa.  I'm a hematologist at the Mayo Clinic, and here today with this roundtable discussion on Patient Power regarding updates in particular for polycythemia vera being discussed at the American Society of Clinical Oncology.  I am joined today by a wonderful roundtable panel of friends and colleagues.  First, Dr. Alison Moliterno from the Johns Hopkins School of Medicine in Baltimore.  Welcome, Alison. 

Dr. Naveen Pemmaraju from MD Anderson in Houston.  Naveen, welcome. 

Dr. Pemmaraju:

Thank you. 

Dr. Mesa:

And then joining we're very fortunate today to have Heidi Cascarano.  Heidi is an MPN advocate diagnosed with polycythemia vera in 2008, subsequently to myelofibrosis.  She brings a particularly important perspective as we try to frame both scientific advances but what it really means to—to Heidi as well as yourselves as MPN patients. 

So to begin with, American Society of Clinical Oncology, I'll frame it for the folks watching, the largest cancer, physician and scientist meeting in the world.  Well over 30,000 attendees here in Chicago covering every topic related to cancer really under the sun.  From diseases everything from polycythemia vera through breast or colon or prostate cancer, but a lot of emphasis in particular on quality of life, on outcomes for patients, health economics and many other issues that are incredibly relevant that go beyond specifically just medicines and treatments. 

But first, specific to our topic today of polycythemia vera, Naveen, why don't you share with us a little bit of the updates specific to polycythemia vera we're seeing at ASCO. 

Dr. Pemmaraju:

Well, thank you, Ruben.  I think there [are] a couple of updates with polycythemia vera.  Probably the most famous one up to this point is the recent FDA approval of the JAK inhibitor, ruxolitinib (Jakafi®), which was shown in the response data set, which was published in the New England Journal [of Medicine] at the end of 2014. 

Here at ASCO what we're all excited about is to see the updated data on that, which the specific concern for polycythemia vera patients are not only how is the drug doing and how are patients doing in the long-term follow-up, but what are the attendant side effects of polycythemia vera.  A few key ones to highlight and discuss, in the New England Journal paper there was highlighted that several patients had a particular infection called herpes zoster, so we want to know and see what the rate of that is over time. 

And then also the rate of nonmelanoma skin cancers, this is something that's a concern to many of our patients. 

Finally, we also want to pay attention to what is the thrombotic, or blood clot, risk that happens over time and to see if this may be also decreased, decreased by the JAK inhibitor therapy. 

I think the final issue in polycythemia vera is the question of transformation to AML.  That is on the minds of some of our patients, although it's a rare, but it is an extraordinarily serious event. And we did discuss earlier at least in the context of myelofibrosis that there is an identification of intermediate and higher risk patients.  So this is something that is of concern to power patients as well, is the risk stratification of polycythemia vera.  And actually, Dr. Alison Moliterno will be chairing an education session tomorrow highlighting the developments in risk stratification of p. vera in our other MPN patients. 

Dr. Mesa:

Excellent.  Well, Alison, why don't you give us a bit of a preview of what you're going to be discussing?  As we think about polycythemia vera, I know from my perspective it's an incredibly mixed group of individuals.  I've had individuals who are 18, you know.  I've had emails from parents of people who are even younger, to individuals really who are in their 80s and 90s.  So how do we assess risk in polycythemia vera? 

Dr. Moliterno:

Well, thank you for that, Ruben, because that's on my mind also in the clinic.  In our clinic, the youngest p. vera patient treated was a 5-year-old girl, and the oldest 92, so it does really cover so many different decades and such a varied mix. 

As we talked earlier today, this is the 10th year of the JAK2 discovery.  Before the JAK2 mutation discovery p. vera was poorly defined based on clinical criteria that were somewhat debatable, and with the discovery of the mutation and the realization that virtually a hundred percent of patients with polycythemia vera have a mutation in the JAK2 gene, that's helped us now really characterize disease better and at least to use that genetic marker to try to understand why some patients have very different courses. 

We've learned a lot about the variability of how much JAK2 you have and how much age and gender really influence the natural history of the disease.  We know—we do understand that younger patients who develop the JAK2 mutation tend to have a more indolent course, but they're still—transformation does apply to them as it did does to older patients who tend to present with maybe a little more aggressive disease or a shorter time to transformation. 

The interesting thing too is there is a big difference between how women and men present with polycythemia vera.  Women tend to present younger.  Maybe they have particular risks for developing polycythemia vera that younger men don't.  That's sort of hard to understand. But as we're accumulating data and observational data, maybe we'll come up with some good answers to that. 

So it is quite a varied mix and lots of modifiers.  When you have a disease that you're going to have for 30 years, just like heart disease, there [are] lots of things outside of the disease that influence how you experience it and the complications in survival.  

Dr. Mesa:

Well, it's a great answer, and it certainly shows I think as we continue to evolve to individualized medicine, you know, realizing how many factors are at play.  The gender issue is a very relevant one.  Our group has been involved with studying the symptoms from MPN patients and [has] data now on about 5,000 patients, 40 different countries, 15 different languages. 

And with that, we see that there clearly is a gender difference in terms of the symptom burden.  Whether patients are in Singapore, Uruguay or Moscow, you know, female patients have a slightly different pattern of MPN-related symptoms than men.  And that may have a variety of factors.  Is that hormonal?  Is that other factors?  Are there other subtle differences but clearly important factors to be very mindful of? 

Dr. Pemmaraju:

And, Ruben and Alison, if I may add one other important point that you both brought up in polycythemia vera is the younger patient, and one item that I am seeing in the clinic more and more is the clot risk and the types of blood clots that folks are having. 

Traditionally, we've always reported and thought about DVTs or deep venous thrombosis or pulmonary embolisms, the more common. But in our patient populations, we're seeing clots in more atypical places, cerebral sinus clots, that is in the brain and head area, clots in the abdominal or GI areas such as the Budd?Chiari or portal venous thrombosis. 

And these clots are oftentimes being diagnosed at the presentation, that is before the MPN or p. vera is diagnosed, and it's leading to entities such as massed polycythemia vera and other entities where potentially a person is presenting with the clot first and then being diagnosed with the MPN later, and then also the issue of the young person going for surgery or pregnancy with polycythemia vera.  I think these are actually very important issues for our patients as we move forward in time. 

Dr. Mesa:

Heidi, we're talking about the variability clearly in terms of how serious or how impactful p. vera is for patients.  Clearly, I know the challenge hearing it from other patients.  When you have a disease that isn't common, you know, many people you run into really aren't familiar with it.  It's not on The View, you know, it's—it's not being discussed on the Today show, so people's familiarity with it is much more limited. 

When people ask you, you know, how serious is polycythemia vera, what do you share with them? 

Heidi Cascarano:

Well, when I was first diagnosed, it was on a random physical. And I had, of course, never heard of it because it's so rare, and I was scared to death because a lot of the information out there talks about a pretty short life expectancy. And you know there's—a lot of information wasn't up to date.  I was very blessed to be diagnosed after the JAK2 discovery, just a few years.  But as you get educated, you learn that there [are] a lot of patients living with it, you know, for many years, which is very reassuring.  And there's so much hope now with all the different trials going on. 

Dr. Mesa:

Alison, I know that there's a tremendous interest in a variety of areas that still remain quite experimental.  There's interest in whether gene therapy could have an impact, although it hasn't been tested yet, or immune-based therapies that are having a very strong impact in other diseases.  Where do these—what are areas that you find that might be hopeful, not necessarily in 2015 but in the near future that could impact a disease like polycythemia vera?  

Dr. Moliterno:

That's a great question.  I think now that we have a target with the JAK2 mutation particularly in polycythemia vera, we have to really focus our efforts and our thinking to how to eradicate this or how to—right now, our therapies have been more to mollify or reduce symptom burden and very effective. And again the trials we've discussed really showed the role that JAK2 signaling—that it is really causal to many of the symptoms, so just lowering JAK2 signaling with JAK2 inhibitors has really translated to a lot of benefit for patients.  But now can we somehow think again a little farther into the future in terms, can we use the JAK2 mutation as an Achilles heel to really get to the root of this disease. 

We know that the disease occurs in a very primitive stem cell, and so we have to get to that level and try to get our therapies to address the JAK2 mutation at the stem cell level, and can we capitalize on an immune mechanism to either elaborate that therapy at the stem cell level or to really use as almost a magic bullet to get to the JAK2 mutation with gene therapy or this CRISPER therapy that now perhaps could actually attack the JAK2 mutation and eliminate the clone.  

Dr. Mesa:

Naveen, we clearly have seen, and you had alluded to the data with ruxolitinib and p. vera, safe effective and approved in second-line setting in the U.S. for people who have failed hydroxyurea (Hydrea®).  In your mind which patients as you're seeing them now, you know, are good candidates for ruxolitinib, as well as how we night see other combinations potentially impacting polycythemia vera. 

But perhaps the first question, as you are in your clinic and maybe there's someone who is far from Houston and participating in a clinical trial is really not a good option for them, who do you consider ruxolitinib for? 

Dr. Pemmaraju:

Thank you.  I think this is one of the biggest questions of our time, now that we do have an FDA?approved drug in this space.  The indication, as you said, Ruben, is for patients who have had either intolerance or resistance to hydroxyurea, and that does have a very specific definition, so of course we're following that. 

I think the patients who really are benefitting from ruxolitinib are those who still do not have the hematocrit control or the reduction in the spleen size after a sufficient trial of hydroxyurea.  The phlebotomy requirements are so high, or the splenomegaly is so great—and in fact these were the primary end points of response trial. 

I think the second group of patients is the patient who has intractable symptoms well, although this was not a primary end point of the study.  It's remarkable the inclusion of the quality life details that showed that a great majority of the patients had improvement in some of these really, really difficult to manage symptoms, and I think that's a really nice area for our patients. 

But again, you made a very good point, which is in patients that have either been inadequate to or intolerant to the hydroxyurea, and the primary end point shows this benefit in terms of the reducing the hematocrit control and the spleen size.  For future directions in polycythemia vera, that's an exciting thing that Alison just mentioned. 

I think another area that's been looked at as a class is the histone deacetylase inhibitors, and this is something we are eager to see more data and follow-up either alone or in combination with other drugs. 

Then of course the drug interferon, perhaps an older drug in this space, but something that may potentially hit to what Alison was talking about, which is actual eradication of the JAK2 allele burden or the clone, so I think a combination of some older drugs and some of these newer drugs, either single agent or by themselves. 

And then finally you and I had discussed previously the MDM2 inhibitors.  This is another new class of drugs that is potentially being tested in polycythemia vera patients as well.  So I think these are some of the other directions to look at as well. 

Dr. Mesa:

So, Heidi, you clearly have heard, and hopefully find hope from all of the different avenues that Alison and Naveen have kind of raised.  You know, as a patient, as you're hearing about different studies and trials, what sorts of things resonate with you as kind of the most important goals or outcomes of the therapy that get you excited that they're hopeful for you as an individual?  

Heidi Cascarano

Well, for me, and I think for a lot of other patients too that I've heard in the support groups, the combination therapy is very exciting.  I'm actually on a combination therapy right now and doing very well.  So I think that most patients are looking for a reversal of the disease, even if there's not a cure, but to reverse of the fibrosis, and if you're in polycythemia vera still, to keep it from progressing to myelofibrosis.  I wasn't on a drug treatment until I progressed, and I do feel like maybe I wouldn't have progressed so quickly if I had been on a drug therapy at the time. 

So I, myself, believe in advocating for early treatment and in making sure to see an expert.  I mean, like you all.  It's so important to get on a good therapy quickly.  

Dr. Mesa:

Well, great.  Well, that's fantastic perspective, you know.  As you have heard there's tremendous amount of advances, both here at the American Society of Clinical Oncology, but I would take away that this is a field that has a very impassioned partnership between physicians, scientists and patients.  There's a lot of advances. 

There are really three major scientific meetings per year that are the—kind of the highlights of the discussion, but the work is always ongoing:  The American Society of Hematology in December; this meeting, the American Society of Clinical Oncology; and the European Hematology Association, so a lot to be hopeful for.  Tremendous advances in polycythemia vera that may have implications clearly across the board not only for MPN patients but for patients with other bone marrow diseases that clearly can overlap as well. 

So I very much would like to thank our roundtable participants, Alison Moliterno, Naveen Pemmaraju, Heidi Cascarano, and on behalf of all of us, thank you for tuning in today.  

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 July 19, 2015