MPN News From ASH 2016: An Update From Dr. Srdan Verstovsek

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Topics include: Treatments and Understanding

Dr. Srdan Verstovsek of MD Anderson Cancer Center shares a comprehensive overview of the treatments for myeloproliferative neoplasms (MPNs) being discussed at ASH 2016. Listen as Dr. Verstovsek discusses the results from COMFORT I & II studies, research around interferon therapy for polycythemia vera (PV), JAK inhibitor studies, new therapies to combat anemia, as well as some of the newer therapies that we will learn more about in 2017.

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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. 

Mary Windishar:

Hello from ASH 2016.  I'm Mary Windishar, and we're lucky today here in San Diego to have Dr. Srdan Verstovsek with us to give us some of the highlights he's seeing as of this Sunday meeting.  So what are you seeing—well, first of all, let's actually get formal about this.  Tell us your title and tell us where you're working. 

Dr. Verstovsek:

So hello, Mary.  I'm Srdan Verstovsek.  I'm a Professor of Medicine in the Leukemia Department at MD Anderson Cancer Center in Houston, Texas, and I do myeloproliferative neoplasms as my topic.  That's what I do in my life.  I see patients and try to eliminate disease or at least help them live with myeloproliferative neoplasms for as long as possible with a good quality of life. 

Mary Windishar:

And so we've got some exciting news on overall survival at today's conference, right?  

Dr. Verstovsek:

Yes, indeed.  We can extend what I said to real information that is being presented here at the meeting.  It is well established that ruxolitinib (Jakafi), a JAK inhibitor is the standard therapy for patients with advanced myelofibrosis, particularly those suffering from symptomatic enlargement of the spleen or very bad quality of life. 

There were two studies that led to its approval.  These studies are called COMFORT?I and COMFORT?II.  Basically, patients were randomized between getting ruxolitinib or getting placebo or any other therapy.  Now, we have a five?year follow?up of these studies that I'm presenting here looking at what happens in terms of survival of these patients. 

Now, we know that patients that are or were exposed to ruxolitinib from the time of randomization live much longer than patients that were not given ruxolitinib.  During the study, there was allowance for patients that were not given ruxolitinib from the beginning to actually get ruxolitinib at some point in time after about a half a year or a year.  That's called crossover.  Now, despite that change from placebo or best available therapy to ruxolitinib we still see significant impact of ruxolitinib on patients' longevity. 

Let me put this in the numbers.  So if the patients were never ever exposed to ruxolitinib in this comparison, they would live on average three years shorter, so there was a three?year expansion of the survival with ruxolitinib.  If there was introduction of ruxolitinib later in their life, that difference was smaller.  It was about a year-and-a-half.  So it seems to me that the message of this presentation is that earlier introduction of ruxolitinib into the patients who have symptomatic myelofibrosis as a therapy is valuable and eventually not that we're going to see only improvement in the spleen and the quality of life but also survival benefit. 

Mary Windishar:

Amazing.  And what about someone who is newly diagnosed?  What should they say to their doctor to make sure that they also have the same benefit? 

Dr. Verstovsek:

This is really an excellent question, because what we have been doing so far and what we are doing in our practice is to treat patients that have already established problems that we need to correct.  Patients with low blood cell count need to have that improved.  Patients with big spleen or symptoms need that to be improved, and here we have ruxolitinib for these two problems.  

The question that you are asking is of primary importance, can we prevent things from happening?  So in the United States we do not do that yet, because there is no real data that would support introduction of any agent, any serious information from clinical studies that would let us do that for prevention of things from developing.  But there is a study in Europe, and perhaps in a year or two we'll know whether there is a value of low?dose ruxolitinib, a JAK inhibitor, which is being compared in placebo?controlled, randomized blinded study in patients that don't have any symptoms or spleen or anything at all.  It's being compared to see whether it can prevent things from developing.  So it's a very hot topic. 

Mary Windishar:

So stay tuned, right? 

Dr. Verstovsek:

Yes. 

Mary Windishar:

All right.  So what about the—there were two Phase III studies that you also feel pretty happy about. 

Dr. Verstovsek:

Now we are talking about polycythemia vera.  Now, this is a little bit more of an easier task to explain.  Polycythemia vera means that all the cells are growing, and because there are too many cells in blood, particularly red blood cells, many have high white cells and high platelets, the risk of a blood clot is what we worry in everyday management of the patients.  The life is pretty long, so we want to prevent any complications during that life from the blood clot or even death.  

So prevention of the blood clotting is achieved usually in a large portion of the patients with introduction of certain medications that would lower the blood cell count, right?  Not everybody needs it, but majority do.  The standard practice is, in the United States at least, to give patients a medication, a pill called hydroxyurea, which is pretty effective. 

Now, there [are] two studies that you mentioned that are being presented here, are prospective randomized studies of patients with PV, polycythemia vera, that need to reduce their blood cell count because of a risk of thrombosis where the comparison is being done between hydroxyurea and what we call long?acting interferon.  Interferon is biological agent, and this long acting means that it's given sporadically.  This is once a week or every other week. 

There are two preparations of interferon that are being compared.  In one of the studies, a randomized study, it was hydroxyurea (Hydrea) versus peginterferon alfa-2a (Pegasys), and the other was hydroxyurea versus ROC peginterferon.  This later one is being done in Europe.  That is coming from Europe.  The first one is from the United States. The results are showing that there is similarity between the approaches.  There is no real difference between hydroxyurea and interferon.  One is not superior than the other.  They are about the same, giving us a hope that perhaps this will lead to wider use and perhaps even approval at some point in time or one of these interferon preparations as a frontline, first?line therapy for patients with polycythemia. 

Mary Windishar:

Why do I think interferon has a bad reputation?  Did it get used incorrectly or unfortunately in the past?  

Dr. Verstovsek:

Well, you are correct in that part.  The interferon is the biological product.  That means actually it is derived from the nature.  We have interferon in our body, and when we have inflammation or infection it gets produced, and we don't feel well, low?grade fevers, fatigue, muscle aches and pains and so on. And this is what happens when you inject yourself with low?dose interferons, not in everybody, not all the time, but it may. 

And in the past the regular preparations of interferon, so it's not a pill, it's injected under the skin, can cause those symptoms in particular and some others in a good proportion of the patients, so people don't like to do that, doctors don't like to do that, so it wasn't much in favor. 

But now we know that, in fact, it can actually affect the disease itself, improve the bone marrow in some patients, decrease number of malignant cells in some patients completely. And the new preparations that are given sporadically, once a week or every other week, are much better tolerated.  

Mary Windishar:

So redemption. 

Dr. Verstovsek:

Yes, it is.  

Mary Windishar:

All right.  And what about anemia? 

Dr. Verstovsek:

Now, anemia for myelofibrosis is a major problem.  When we assess a need for therapy in patients with myelofibrosis there are usually three aspects.  Either there is a huge enlarged spleen that is causing problems, symptomatic splenomegaly, that is very poor quality of life, inability to walk, fatigue, weakness, bone aches and pains and that sort of thing, not too nice a picture.  And there is a bone marrow failure.  Bone marrow produces blood cells, and a major problem is anemia. 

So usually when we assess the efficacy of any medication is assessing the benefit on these three parameters.  So we know the JAK inhibitors improve the splenic symptoms but not anemia.  Patients with myelofibrosis can be severely anemic and transfusion requiring, and we don't have good therapies for that.  

At this meeting, there is an oral presentation—that means presentation in public, in oral session—of a pilot study of a new medication called sotatercept.  Kind of funny name, but it's called sotatercept.  It's injectable under the skin once every three weeks.  A similar medication to that is being developed in a cousin to myelofibrosis, a different disease called myelodysplastic syndrome.  So sotatercept appears in a very small study, pilot study, to improve anemia in about 40 percent of the patients.  

Not having anything to offer to patients and having this pilot study gives me hope that further enrollment of more patients and further development of this type of medication when we have nothing will give us a medication eventually to give patients, perhaps even in combination with JAK inhibitors to tackle all the problems we have with myelofibrosis.  

Mary Windishar:

And what's it like being Dr. Serge and able to tell your patients some of this good news? 

Dr. Verstovsek:

We are very optimistic.  We had some setbacks, no question about it.  There are some other JAK inhibitors that were tested in advanced studies that did not show the difference for the patients to great extent, some extent but not great extent, so it's questionable whether they will be approved.  

There are other JAK inhibitors that are following the path.  There is one called NS?018, which is being tested in the second line after ruxolitinib in patients with myelofibrosis, and there are, as you'll see, new medications coming along. So we when we look at the past and now can say that we have made a major difference for the patients over the last five to 10 years since the discovery of the JAK2 mutation and hopefully next five or 10 years will bring us a number of new medications to patients.  

Mary Windishar:

Well, we hope you'll be here to help us work through it and understand what's going on.  Thank you so much. 

Dr. Verstovsek:

Thank you.  We'll fight it together.  Thank you very much. 

Mary Windishar:

Good.  I'm Mary Windishar from ASH 2016.  

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 January 4, 2017