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Thriving With MPNs: Your Role in Managing Your Treatment and Care

Thriving With MPNs: Your Role in Managing Your Treatment and Care from Patient Empowerment Network on Vimeo.

 How can patients thrive with a myeloproliferative neoplasm (MPN)? Dr. Jeanne Palmer discusses treatment approaches, strategies for managing disease symptoms and treatment side effects, and advice on how patients can be proactive in their care.

Dr. Jeanne Palmer is a hematologist specializing in myeloproliferative neoplasms (MPNs) and bone marrow transplant at the Mayo Clinic in Arizona. Dr. Palmer also serves as Director of the Blood and Marrow Transplant Program and is Vice Chair and Section Chief for Hematology. Learn more about Dr. Palmer, here.

 

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Transcript:

Katherine Banwell:

Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today, we’re going to talk about how to live and thrive with an MPN. We’re going to discuss MPN treatment goals and how you can play an active role in your care. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. 

Well, joining us today is Dr. Jeanne Palmer. Dr. Palmer, welcome. Would you please introduce yourself? 

Dr. Jeanne Palmer:

Thank you so much. I am so happy to be here and to help participate in this. My name is Jeanne Palmer. I am a hematologist at Mayo Clinic in Arizona. I specialize in MPNs as well as bone marrow transplant, and I am thrilled to be here. 

Katherine Banwell:

Thank you for taking the time out of your busy schedule to join us today, Dr. Palmer. We start all of the webinars in our Thrive series with the same question and that is, what does it mean to you to thrive with an MPN? 

Dr. Jeanne Palmer:

I think living with an MPN can be very difficult. I think there is a number of things. First of all, there’s always the worry of what’s going to happen in the future. Many of these MPNs can start as fairly, for lack of a better term, as benign issues and can convert to something much more serious. So, I think living with that sort of timebomb in the back it can be extremely stressful. So, figuring out how to live with the fact that there is some degree of uncertainty. 

I think the other thing is making sure to understand your disease. These are very rare disorders and even if you go to a hematologist-oncologist specialist, a lot of times they don’t have all the information because they don’t see a lot of them every year. So, it’s really important to make sure that above and beyond that you understand what’s going on in your body so that when new things happen, new symptoms happen, you’re able to really address them as opposed to sort of living with something that may make you feel poorly that’s not being addressed.  

So, again, I think the biggest piece of this is seeing how do you live with uncertainty and how do you make sure you understand your disease well enough that you know what’s going on in your own body. 

Katherine Banwell:

Yeah. That’s helpful to understand, especially as we move through today’s program, and we’re going to cover the three classic MPNs, polycythemia vera, essential thrombocythemia and myelofibrosis. One part of thriving with an MPN is managing the symptoms of the disease. Would you walk us through the common symptoms of each of the MPNs? Let’s start with essential thrombocythemia. 

Dr. Jeanne Palmer:

Right. So, there are a number of shared symptoms throughout all the diseases and when we start to figure out how to categorize them, they call into several different categories. The first one is inflammation-related symptoms. We know that the inherent pathway that’s dysregulated or that causes these diseases to happen can also result in significant inflammation in a person, that can result in things like fevers, night sweats, weight loss, and overall feeling really fatigued and poorly, which is something that it seems to be much more prevalent in patients with MPNs, all sorts of them, actually. 

The next set of symptoms is related to microvasculature, so all the little blood vessels. And sometimes we think, oh, maybe that’s because there’s too many red blood cells or platelets and the blood become viscous. It’s probably more related to the actual dysregulation of that JAK2 pathway, which is inherent to all the myeloproliferative diseases and as a result, the little blood vessels can clamp down and that can give people headaches, visual changes, numbness and tingling in the hands and feet, and even can cause sort of a painful rash called erythromelalgia in the body. 

So, these are things that can happen that are probably less appreciated side effects of the disease. And finally, there’s spleen-related symptoms. The spleen is in the left upper quadrant of the abdomen and it’s an organ that generally is about 12 centimeters in length, 10 to 12, but in patients with myeloproliferative diseases it can be enlarged. And as a result of an enlarged spleen people can have feeling like they get fuller early. So, if you’re eating a meal, all of the sudden you can only eat half of that meal versus the whole meal.  

Discomfort or pain in the left upper quadrant. Sometimes it’s much more noticeable when you like bend over to tie your shoes. And then sometimes people can actually, when the spleen gets really big, the blood flow can be impaired towards the end of it which can cause some of the spleen tissue to die, and that can be painful. So, these are things that if somebody does start to notice that they’re having fullness in the left upper quadrant, pain, stuff like that, that that may be related to spleen symptoms. 

Katherine Banwell:

What about PV or polycythemia vera, what are the symptoms? 

Dr. Jeanne Palmer:

So, all of these sorts of relate to all of the myeloproliferative diseases. So, one other one that I didn’t mention, and this is actually more in PV than others, is itching. Itching can be absolutely unbearable when somebody has PV. It’s particularly noticeable after taking a shower. So, a lot of times I’ve met patients who are like I haven’t been able to take a shower in years, because it causes such a high degree of itching. 

Katherine Banwell:

Why a shower? Is it different from having a bath?  

Dr. Jeanne Palmer:

Water on the body that can cause the problem. So, if people take hot showers, it’s even worse. Although I think that people sort of react to it differently. Usually what patients end up doing is more like sponge bath type of things, rather than actually being exposed to the water. 

Taking colder showers or cooler showers can sometimes help mitigate that. But the itching, and even in the absence of a shower, people can have pretty severe itching, and that can also be one of the major side effects. 

Katherine Banwell:

Much of the time the chosen treatment for MPNs manages the symptoms of the condition. I’d like to review the different types and classes of treatment for the three MPNs. So, let’s start with essential thrombocythemia again. When is it time to treat, and what are the options available?  

Dr. Jeanne Palmer:

Right. So, with essential thrombocythemia, that’s the disease that sometimes we don’t need to treat. 

So, we basically have a risk stratification system and this risk is based on age, history of a blood clot, the presence or absence of a JAK2 mutation. So, for example, if somebody is 28, does not have a JAK2 mutation, which is again one of those driver mutations, and never had a blood clot, they actually don’t necessarily need to do anything and just be monitored.  

Somebody who is less than 60 and has a JAK2 mutation or who is greater than 60 and does not have a JAK2 mutation, in that setting, a lot of times you can use aspirin. Now, it gets a little bit gray in terms of that over 60 without the JAK2 mutation with regards to whether at that point you really should start taking some medicine to lower the platelets. 

Now, if somebody has a JAK2 mutation, is greater than 60 or has had a blood clot, hands down they need to take medicine to lower the platelets, in addition to aspirin or whatever blood thinner they may need. So, for example, if you have a blood clot in a vein, a lot of times you need to take a blood thinner and that will be a lifelong thing. And again, we do these risk stratifications because we know there is a certain risk of clotting associated with the risk of essential thrombocythemia. 

So, for example, somebody who is less than 60 and does not have a JAK2 mutation, never had a clot, their risk of clotting is probably very close to that of the normal population. Whereas if you’re higher risk and have a JAK2 mutation and greater than 60 or have had a history of a clot, the risk of clot is probably about 4 percent per year. So, this is something that can vary quite widely, and even though that 4 percent per year on the short-term doesn’t sound like a lot, if you take it additive over years, that’s why we generally try to be aggressive about lowering the platelets.  

In lowering the platelets, the goal is to get less than 400 and doing that can be done through several different medications. The most commonly used medications is a drug called hydroxyurea, which has been around for a number of years, and a drug called anagrelide which is probably a little less commonly used, because it has some more GI side effects and headaches associated with it. 

In some cases, especially in younger patients with this disease, we can consider using interferon, which is an injection of a cytokine, which are one of the chemicals that regulates the immune system within the body. But this interferon can actually help lower the platelets and there is a question of whether it may affect the biology of the disease as well. 

Katherine Banwell:

Let’s turn to polycythemia vera or PV, what are the different options available for treating it? 

Dr. Jeanne Palmer:

So, for polycythemia vera, everyone needs to be on aspirin. 

And additionally, everyone needs to make sure to keep their blood count low, to manage their hematocrit, which is one of the measures of red blood cells. So, in men it’s generally recommended to keep below 45 and in women it’s recommended to keep below 42 percent.  Now, the studied number was 45 percent and that was a study that was done, I don’t know, it was probably about 10 plus years ago, that actually showed that by keeping the blood hematocrit less than 45 percent you reduce the risk of having negative events like cardiovascular events and heart attacks. Because women tend to run with a lower blood count than men, it’s been extrapolated that 42 percent should be the number used for women. 

Now, this can be done by phlebotomy, which essentially is bloodletting. It’s kind of like donating blood except for that the blood unfortunately can’t be donated to anybody, it has to be discarded. But the phlebotomy is one way to do that, and the reason that works is because it makes somebody iron deficient. So, whereas if this is normal, if you’re iron deficient you become anemic. If your baseline hematocrit is here, making you iron deficient brings you back to normal. So, even though we always associate iron deficiency with anemia, iron deficiency in the setting of polycythemia vera is actually kind of a treatment of sorts. 

Now, once somebody gets above 60 and 60 seems to be sort of the magic age in these diseases, once somebody gets above 60, it is recommended that cytoreductive therapy is used, which means therapy or treatment that will bring down the red count. And again, for this one, hydroxyurea is an option as well as interferon. And there is recently an approval, actually FDA approval for a newer interferon called ropeginterferon or Besremi, which can help just bring down the red blood cells but it is the first interferon that’s actually been FDA approved for this indication. 

Katherine Banwell:

Are JAK inhibitors used as well? 

Dr. Jeanne Palmer:

They are. So, if somebody doesn’t respond well to hydroxyurea, the approval for ruxolitinib is actually for patients who have failed hydroxyurea. Although it’s something that we often consider especially in people who have a lot of symptoms. So, the itching, one of the things that can really help itching actually is Jakafi. If people have night sweats, they have weight loss, spleen related symptoms, those are the patients that will benefit from Jakafi. Additionally, if they are on hydroxyurea and can’t seem to get control of their blood count, Jakafi is a good option to help control the blood counts as well. 

Interferon is a very nice option because there’s great data that shows that you may actually be able to lower the percentage of JAK2 burden. 

So, we’d look at something called an allele burden, which is the percentage of cells that are involved – have the JAK2 mutation. Now, we don’t know whether lowering this percentage necessarily translates to long-term better survival, but I think there is enough data out there, and there is a good biologic underpinning for saying that this actually can help. But yes, Jakafi is another thing. 

And the really exciting thing is that there is a newer agent called rusfertide, which is a hepcidin mimetic, which is basically taking a protein in your body that helps metabolize iron and by making it externally and giving it to somebody that it can actually help bring down the hematocrit without having some of the other side effects we know with some of the other medications. That is currently in Phase III studies, so hopefully in the next couple of years we’ll see approval for that. 

Katherine Banwell:

Oh, that’s great news. And finally, how is myelofibrosis treated? 

Dr. Jeanne Palmer:

So, myelofibrosis is a little bit of a different animal. When you have something like essential thrombocythemia or PV, a lot of this is managing symptoms, preventing blood clots, but if you do appropriate treatment and management of these diseases you could probably live close to a normal life expectancy.  

So, I never typically pin a survival on it. With myelofibrosis, it’s a little bit different because there is a survival. Instead of saying you can live close to normal life expectancy, it backs up to saying how many years do I think you can live with this disease. Now, of course, we are horrible at predicting how many years anyone can live, so we have to take that all with a grain of salt. But we can at least sort of risk stratify people. 

And the first thing that’s really important is to figure out whether somebody is a transplant candidate or not and if, based on age, disease risk features, stuff like that, or whether we think they ever will be a transplant candidate. So, that kind of helps us sort of think about what your path moving forward is.  

Now, the current FDA-approved treatment for myelofibrosis, there are three JAK inhibitors approved, which is like Jakafi, which was the first approved one but there is also Inrebic or fedratinib and Vonjo or pacritinib and these have all been approved over the years. 

The role of JAK inhibitors and treatment of myelofibrosis is symptoms-based. So, for example, a lot of patients with myelofibrosis will have weight loss, night sweats, big spleens, really feeling fatigued and poorly and in this setting, the JAK inhibitor can be very helpful. And you don’t have to have a JAK2 mutation, a lot of times people say, well, I don’t have the JAK2 mutation so how can a JAK inhibitor help. So, the JAK inhibitor works on this pathway, which is called the JAK/STAT pathway, irrespective of mutation. 

So, if you are having symptoms and you have myelofibrosis, JAK mutation, excuse me, the JAK2 mutation does not predict who is going to have a response. And people who, regardless of which mutation you have, may actually benefit from it. 

So, the JAK inhibitors, though, are extremely effective at reducing symptom burden as well as reducing the spleen size. And we know that if a spleen is big and we can make it shrink that, that probably is a surrogate marker for living longer, and I think it’s because inflammation does a lot of wear and tear on the body. So if you can reduce the inflammation and the spleen shrinks, which generally go hand in hand, then you might help somebody live longer. It is not changing the biology of the disease, though, however, it doesn’t change the pathway and that this disease is kind of projecting ahead in terms of creating – it changes, as it goes along, may acquire new mutations or something like that which makes the disease become more serious. 

Right now, the approved therapies for it are JAK inhibitors and the Jakafi, ruxolitinib was the first one approved. Inrebic was approved several years back, or fedratinib. 

And then the most recent one that was approved is Vonjo or pacritinib and that’s a drug that is a JAK inhibitor that is actually very good for people with low platelets. The reason I bring that up is because if we think of what’s the biggest limiter of JAK inhibitors, JAK inhibitors bring down red blood cells, and they bring down platelets. So, when somebody has low platelets it’s very hard to use a JAK inhibitor, because we’re not really able to increase the dose well enough to get that inflammatory reduction because of the fact that the blood counts will drop too low. 

So, now drugs like Vonjo exist which, due to several other mechanisms associated with the drug are actually much more tolerated in somebody with low platelets. So, if you have low platelets, you can actually take the Vonjo, hopefully get the same degree of JAK inhibition to help the spleen shrink, help the symptoms get better without necessarily making the platelets substantially worse. A lot of times they do drop, it doesn’t help bring up the platelets, but it does help people tolerate more JAK inhibition, which ultimately will help with symptoms.  

Dr. Jeanne Palmer:

So, one thing I also wanted to add about myelofibrosis treatment is sometimes people present, they don’t have a lot of symptoms, they don’t have a lot of spleen related problems but they have anemia or low blood counts and these can be incredibly hard to treat. 

Even with symptoms and low red blood cell count or anemia or low platelets, it can be challenging to treat because many of these medications lower that. To treat the anemia there are several things that we can do. One of the first ones is using erythropoietin, and so there are many agents, they go by the names of like Procrit or darbepoetin alfa, that actually stimulate red blood cell growth by – like we give a recombinant hormone that helps red blood cells grow. This is normally something produced by the kidney. 

So, one thing that’s important before going on one of these injections is to make sure that the kidney is not already producing enough. So, for example, if the kidney said, oh geez, I really need more red cells and is making lots of this hormone, erythropoietin, giving more of it is not going to help the system. But in people who don’t have a really high level it can be very beneficial. 

The other thing that can help with anemia, specifically, is a drug called danazol.  

It’s been around for a very long time. There are multiple presumed mechanisms of action, but one of them is that it is kind of a testosterone derivative. So, this is a medicine that can often help increase red blood cells in probably about 40 percent of people, and it’s a pill that you take twice a day. 

Another option, sometimes we use thalidomide or lenalidomide (Revlimid). These are medications that have been used quite frequently in the setting of multiple myeloma and even a little bit in myelodysplastic syndrome, so some other blood disorders.  

But in the setting of myelofibrosis, they can be helpful with anemia and sometimes are combined with prednisone or a corticosteroid. And then finally, in terms of drugs that are being tested and hopefully will be approved at some point in the future. There is a drug called momelotinib, which is another JAK inhibitor that actually has some mechanisms that may also help improve hemoglobin. 

So, this is something I’m really looking forward to and we anticipate may be approved by the end of the year. And finally, there is another drug called luspatercept (Reblozyl). Luspatercept may work in the setting where your kidneys are already producing enough erythropoietin. So, the luspatercept is an injection that you receive once every three weeks.  

It is currently FDA-approved for the treatment of myelodysplastic syndrome but this is something that has been shown to have some efficacy in myelofibrosis as well. So, this could be another therapeutic option for patients with myelofibrosis. 

It is also important, especially for people who have polycythemia vera myelofibrosis to make sure that your iron has been checked and B-12 has been checked, because just because you have a bone marrow disorder doesn’t necessarily mean you don’t have a nutrition deficit that may be able to help improve your hemoglobin somewhat. But these are important things to talk to your doctor. I do not recommend just starting to take iron or B-12, however, if you’re anemic because in many cases you are not deficient and taking too much iron can actually be damaged. 

Katherine Banwell:

Yeah, that’s great advice.  

When would you consider a stem cell transplant? 

Dr. Jeanne Palmer:

So, the stem cell transplant is based on disease risk. There is a number of ways we assess disease risk. The first two ones that were published a number of years back were the DIPSS score, which is Dynamic International Prognostic System Score, or the DIPSS Plus, which basically is the DIPSS and then you add to it a few other clinical features. This symptom score is based largely on things that we can see without even a bone marrow biopsy, so things like symptoms, age, number of white blood cells, whether somebody has anemia. And then the number of something called blasts, which is very immature white blood cells. The DIPSS Plus takes into account low platelets, need for transfusions, and chromosome abnormalities, which is the only test among that that needs to be from a bone marrow biopsy. 

Now, these were created prior to Jakafi being commercially available. So, we have to take a little bit of a grain of salt with those because of the fact that Jakafi probably has changed how long people can live with this disease. 

Now, more recently they’ve tried to account for these other molecular changes. So, when we take the genetic landscape of these diseases, we have the known driver mutations, so the JAK2 mutation which I have talked about, also calreticulin and MPL.  

These three mutations all affect that one pathway, the JAK/STAT pathway, so they all affect the pathway that drives the disease and they are known to be kind of mutually exclusive and definitely contribute to the formation of the disease.  

Some of these other mutations are called somatic mutations. They could be checked by things next generation sequencing or genetic analysis. There’s a number of different names that people use for this testing, but we look for mutations that are present and these mutations, number one, can sometimes tell us risk. So, there’s certain mutations that are high risk. Other times it can actually give us other opportunities for therapy, especially of the disease progresses. But these mutations are important to know for risk stratification. For example, if somebody has DIPSS score that is maybe not super high risk, but then they have one of these mutations, we know that that probably makes their disease a little bit more aggressive. 

And that’s when we think about transplant, is when we know that the disease probably has an average life – when somebody gets to the point in their disease where we estimate their life expectancy is around five years, recognizing that we’re not very good at this. That is the type of point when we start to think about transplant. But the timing of transplant is something that’s extremely difficult and a very personalized decision. It’s something that it’s really important to understand the disease risks, how we assess them and the caveats of these disease risk assessments as we move forward planning and timing of transplant and that’s something that is, again, a very, very important discussion to have at length with your physician. 

And I always recommend, there is quite a few of us out there who actually specialize in transplant for myelofibrosis and having discussions with somebody who really understands the biology of the myelofibrosis and important because it’s very different than a lot of the other diseases that are transplanted.   

Katherine Banwell:

Yeah. Well, speaking of that, patients can sometimes feel like they’re bothering their healthcare team with their comments and questions. Why do you think it’s important for patients to speak up when it comes to symptoms and side effects?  

Dr. Jeanne Palmer:

Well, there is a lot of things. This is a disease, again, that we can direct our therapy many times towards symptoms, and so when we think about how do I direct my therapy, so how do I treat somebody, symptoms are an incredibly important part of it. And there is nothing worse than having a patient come and see me who I see every six months, because they’ve been pretty stable and they’re like, “Oh, for three months I’ve been feeling awful.” And you’re like, well, “Why didn’t you let me know, we could do something about this?” 

So, if there is something that doesn’t feel right, it’s very, very important to talk to your healthcare provider. I would much rather be bothered and handle something earlier on than miss something and really have a lot more catch-up to do afterwards. 

The other thing is symptoms may indicate a blood clotting event. We know that patients will have a higher risk of blood clotting. These are extremely important to identify early on because if they go unchecked, they can cause more damage. 

Katherine Banwell:

With many of the treatments available as pills now, patients have a role in self-administering their treatment regimen. What happens if a patient forgets to take a medication? Does it impact its effectiveness? 

Dr. Jeanne Palmer:

Generally no. I think the ones that would are certain blood thinners you really don’t want to miss and you don’t want to miss the doses on it. With drugs like Jakafi, if you miss one dose you probably won’t notice it, but if you miss multiple doses you can actually get very sick from that. So, some of these medications are really important to be consistent on. 

Now, I know this could be a challenge. I mean I don’t take very many medications and I sometimes have a hard time keeping track of what I take, so I know that this can be a difficult thing to do. So, one thing is if you really find you’re struggling with it, setting an alarm on your phone or your Apple Watch or whatever… 

Katherine Banwell:

…device. 

Dr. Jeanne Palmer:

Device you have can be a really helpful way of doing it. Also having a pill box. They make pretty amazing pill boxes these days that can account for taking drugs once a day, twice a day, three times a day. I’ve even seen them up to four times a day, although generally the most you’ll probably have to take a medicine for a myeloproliferative disease is twice a day. But those are different ways that can really help make sure you’re consistent about taking your medication. 

Katherine Banwell:

And if a patient misses a dose, do they need to call their healthcare team and let them know? 

Dr. Jeanne Palmer:

Not just for one missed dose. If like, for example, they’re run out and they say, “Oh, geez, I don’t have any and many of these drugs are specialty pharmacy,” so they need to be mailed, and you know that you’re going to be missing it for a while. Or let’s say you look at your pill bottle and go, “Oh shoot, I only have so many pills left,” it is helpful to call because a lot of times, for example, if somebody is on Jakafi and they know they’re going to run out of their pills four days before they’re going to get their next shipment in, then what I sometimes do is I lower the dose a little bit to make sure they maintain a dose throughout that time. 

But this is something you definitely want to do under the advice of a healthcare provider. You don’t want to just all of the sudden go, “Oh, well I’m going to run out so I’m just going to change my dose,” and kind of do that. 

Katherine Banwell:

Yeah, yeah. We received some audience questions prior to the program today. This one is from Jacqueline, “What can I do to minimize pruritus or itching due to PV? A typical histamine blocker like Claritin or Zyrtec has done nothing whatsoever.” 

Dr. Jeanne Palmer:

Yeah. Unfortunately, the itching of this is not as much mediated by an allergic type reaction or histamine. It’s a lot related to that microvasculature, those tiny little blood vessels. Things like avoiding hot showers, as we talked about, taking cooler showers or not even taking showers, just like cleaning yourself with a washcloth can be helpful. There are certain medications that we can use sometimes that help. 

Now, first of all, Jakafi is extremely effective for itching. Of course, it does have side effects. It’s not always approved for your disease, so for example, it’s not approved for essential thrombocythemia. But JAK inhibitors can be helpful in that setting. There are also medications like Gabapentin, which is a medicine that we use to treat peripheral neuropathy and that can actually be helpful because actually the itching, a lot of it is related to nerves not functioning right, so gabapentin can be helpful. 

And a really old-school medicine that I sometimes use, especially if the itching is most prevalent at night, is a drug called Doxepin and that’s been around for a very long time, but it can be extremely sedating and has to be used with caution, especially in patients who are older. 

Katherine Banwell:

Here is a question from Daniel. “How often should a person with PV have hematology appointments, and how often should you have blood tests?” 

Dr. Jeanne Palmer:

Well, that is something that you need to discuss with a provider, because everyone’s a little bit different. If I have somebody who I’m managing on a medication, they’ve been rock solid stable, it may be every few months that I check blood and maybe every six months that I see them.  

If I have somebody who have been particularly difficult to control and I’m sort of adjusting medications or they’re having symptoms, then I try to check blood more regularly, like on a monthly basis. But again, this is something that – I have checked blood as frequently as every two weeks, especially in somebody who has an extremely high red blood cell count that I’m trying to lower. I have checked blood as infrequently as every three months. Again, in somebody who is not undergoing treatment, say, for example, who has essential thrombocythemia, sometimes I check blood even less. So, it really is something that can vary from every two weeks to every six months. 

Katherine Banwell:

Okay. Katie had this question. “What are the signs of progression from PV to MF or AML, both clinically and in blood tests, and when do you need a new bone marrow biopsy to check for this happening?” 

Dr. Jeanne Palmer:

So, in terms of progression, there are several things that we see happen. 

I think most importantly is, let’s say you have PV, and you’ve always been on medication, and it’s been hard to control. And all of a sudden, you don’t need medication to control it anymore, or the same thing for essential thrombocythemia. You have been taking medication, and all of a sudden your platelets go down, and you don’t need to take drugs anymore. A lot of times people are like, “Oh, that means I’m fixed and I’m well,” not necessarily, you really need to make sure to talk to your healthcare provider and potentially get a bone marrow biopsy. 

Now, the other thing – sometimes the blood counts will actually drop too low, so you’ll have somebody who has PV, who has always been too high and then all of the sudden they come in, and their hemoglobin is very low, and they’re anemic, and that’s another situation where you do that. So, anytime the blood counts start to drop is concerning.  

Now, it’s a continuum, so the blood counts may drop as you’re at the point of transitioning but it doesn’t – it’s not like if your blood count is dropping you say, “Oh my God, I have myelofibrosis, I need a bone marrow transplant tomorrow.” That’s not necessarily the case. This is generally a transition type process. 

Also when the spleen starts to get enlarged. Now, the spleen can be enlarged even in the setting of just ET or just PV, so spleen enlargement does not necessarily mean you’re transforming, but it can be one of the things that we would see that would indicate that. 

Katherine Banwell:

Okay. 

Dr. Jeanne Palmer:

And then finally white blood cell count increasing can often be a sign of that. Now, in terms of progression to AML, that is generally something we’ll see in the blood. AML or acute myeloid leukemia, is indicated by the presence of blasts at greater than 20 percent. Now, many patients with myelofibrosis, in particular, but even PV and ET, may have blasts in their peripheral blood. Blasts are normal. If I did a marrow on every healthy person out there, they are going to have some blasts, because these are the first part of the development of white blood cells. So, they’re like baby white blood cells. But what the problem is, is when they start to grow too much. 

And so in the setting of myelofibrosis and even sometimes with these other diseases, the blasts will be in the peripheral blood primarily because the bone marrow is damaged and doesn’t hold them in very well. It becomes AML when it gets greater than 20 percent, so that blasts of greater than 20 percent in the peripheral blood or in the bone marrow but a lot of times we find it in the peripheral blood is where we indicate this has progressed to AML. 

Katherine Banwell:

Yeah. 

Dr. Jeanne Palmer:

Blasts of greater than 10 percent are also something that we really want to pay attention to, because that would suggest that the disease is starting to become more aggressive. Now, blasts vary, so for example, I’ve had patients go up to 11 and then drop back down to 3 or 4, and then they say around 3 or 4 or 5. So, you always want to make sure to double-check because one blast count at 11 percent, whereas it’s very important to address, may not necessarily reflect that you need to change in treatment at that time. Again, these blood tests, I always tell people, do not freak out over one blood test.  

Make sure you get at least a couple of them to really confirm what you are looking at. 

Katherine Banwell:

Thank you, Dr. Palmer. And to our viewers, please continue to send in your questions to question@powerfulpatients.org and we’ll work to get them answered on future webinars.  

Dr. Palmer, was we close out this conversation I wanted to get your thoughts on where we stand with progress in helping people live longer and truly thrive with MPN. What would you like to leave the audience with? 

Dr. Jeanne Palmer:

So, I think that the first thing is make sure you understand your disease. Don’t hesitate to ask for a second opinion. It’s always good to make sure you talk to someone who can really explain so you feel like when you go home you understand what’s going on in your body. Make sure you understand what symptoms to look for, what things to be aware of, because a lot of times people come in and they have no idea that, oh, these symptoms are actually related to their disease. 

The other thing to make sure is that you’re very honest with your provider on how you’re feeling. A lot of times people come in and they say, “Oh, how are you feeling?” “I feel fine,” but then they start to ask very specific questions and they’re like, “Oh yeah, I’m really tired, my fatigue is an 8 out of 10,” or something. 

So, make sure you’re really honest with your provider. When they ask you how they’re doing, this is not a social visit, this is a visit where they need to know your symptoms, so you don’t need to say I’m fine like you normally would if you were walking down the street. 

The next thing is to always make sure to know where there’s clinical trials because we are making enormous great leaps and bounds in this field. It’s a really exciting time for myeloproliferative diseases, and there’s a number of new drugs that are being tested and coming out. So, it’s always important, if the opportunity is available and you can do it, clinical trials are a great way to get treatment. 

Plus, you are giving back, because these are things that help us learn whether something works or not. So, you’re not as much a guinea pig, you never get a sugar pill. It’s one of those things will you will always get the treatment you need and then they may add something to it or you may be in the situation where there is no treatment, so they try something. 

But clinical trials, I have to emphasize, are a great way to get therapy and really are how we know everything that we know about treatment for these diseases. 

Katherine Banwell:

Yeah. It sounds like there’s a lot of progress and hope in the field.  

Dr. Jeanne Palmer:

Oh, absolutely. 

Katherine Banwell:

Thank you so much, Dr. Palmer, for joining us today.  

Dr. Jeanne Palmer:

You are very welcome, my pleasure, and it’s always fun to do these things, so thank you for having me.   

Katherine Banwell:

And thank you to all of our partners. To learn more about MPNs and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell, thanks for joining us today. z

Advice for Hesitant MPN Clinical Trial Participants

Advice for Hesitant MPN Clinical Trial Participants from Patient Empowerment Network on Vimeo.

What should MPN patients know about clinical trials? Dr. Claire Harrison from Guy’s and St. Thomas’ Hospital in London shares information about the varying degrees of clinical trials and advice to those who are hesitant about clinical trials.

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Transcript:

Dr. Nicole Rochester: 

It’s said that clinical trials are tomorrow’s medicine today, and you’ve already kind of alluded to the importance of clinical trials as it relates to MPN. What would you say to an MPN patient who is on the fence or may be concerned or afraid of participating in a clinical trial?

Dr. Claire Harrison: 

It’s right to be cautious and, you know, careful because ultimately it’s a huge privilege as a clinician that involves patients in clinical trials that my patients trust me and trust my team to look after them with something that is experimental, but remember there are varying degrees of experimental. Most clinical trials are not first in man, you’re not a complete guinea pig, it may be a drug, for example, navitoclax is in clinical trials mainly for myelofibrosis also ET and PV but that is a drug that has been used for thousands of patients, for another indication so talk to your healthcare team, if you don’t find the answer from the primary person that you’re used to dealing with, find someone else, be linked to somebody you trust and that you have a good relationship with, take someone with you to the consultation, write down the questions I’m so sure you say this all the time, don’t you Nicole to the people that you talk to, but write down your questions, don’t be afraid to ask them again, there is no stupid question in this context, you will be given a 30-plus page booklet to read, and I lost count of the number of times, my patients go, yeah, I’ve got this, or I trust you.

Actually, you know, you need to read it…we are experimenting on you, and you need to read that and understand. And you need to understand, what happens if I go on the control arm, will I be able to cross over? How many visits will I have, will I have to pay for those visits, etcetera. It’s all really important. But ultimately the relationship with your healthcare provider is important, and using an advocate is really important too.

Dr. Nicole Rochester: 

I agree 100 percent. So important, these are things that I talk about all the time, so I really appreciate that you highlighted that, and just the importance of patients taking an active role in their medical care and also the trust that is required between the patient and their treating providers. So I really appreciate that. Do you have any examples, Dr. Harrison, in your own practice of successes with MPN patients who have participated in clinical trials? 

Dr. Claire Harrison: 

Oh yes, I think I started doing clinical trials, well golly, a long time ago. I think my first clinical trial, probably the records were written parchment to be honest, but we’ve still learned a lot from that, so that was an ET study. It was from that study we understood about the JAK2 mutation, and we understood how patients behave differently. I think probably the most gratifying thing for me was being involved in the JAK inhibitor studies in myelofibrosis and being involved in delivering ruxolitinib and Jakafi to patients and seeing the benefits for those patients. 

Big things, you know, there are patients who are alive because they took part in that trial today, I think, but there are also patients for whom small things were also really important, so as a patient, that’s important to define what is the benefit you want to get. So one of my first patients, you haven’t been able to have a bath or a shower for years, because he had terrible what we call aquagenic pruritus, itching induced by contact with water, we called him two days after he started ruxolitinib (Jakafi), and he was in tears, he could take…or you can take it out.

These things are really important. Like myself, I can imagine not being able to dig it out, I would either be very tough for another patient, it was, well, I looked really skinny because I’d lost loads of weight and I put weight on, and body image was really important as well, but then the small things like being able to be…participate more in family activities is really, really important too. 

What Are the Unmet Needs in Access to MPN Care?

What Are the Unmet Needs in Access to MPN Care? from Patient Empowerment Network on Vimeo.

Which areas of MPN care still need improvements to access? MPN expert Dr. Claire Harrison from Guy’s and St. Thomas’ Hospital in London explains patients who still experience barriers to care and what can be done to reduce access issues.

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Advice for Hesitant MPN Clinical Trial Participants


Transcript:

Dr. Nicole Rochester: 

What would you say are the unmet needs in access related to MPN and care, specifically as it relates to clinical trials, and what can we do to address those unmet needs?

Dr. Claire Harrison: 

Well, I think there is a problem with rare diseases in terms of geographical access to trials, and we often find patients have to travel a long way. I know that’s true in North America as well as in Europe. And we’re very lucky in our geographical locations, but in some parts of the world, some companies or doing not open clinical trials, so I think there’s an access issue. 

I think also there is something about patients have to meet rigid entry criteria for clinical trials, and so oftentimes in myelofibrosis, for example, commonly patients who fail ruxolitinib (Jakafi) have a lower platelet count, and that is often an exclusion criteria. Those criteria are there to try to get a uniform population of patients in a trial, but it can feel like you’re excluded as a patient, and it can feel very tough and for your health care team that we can’t include you in a clinical trial. We also have to remember that it is there for safety purposes, so if there is a lower limit for platelet count, that’s often because the drug might affect platelet count. It is really important that we have a broad spectrum of trials available and that we try to increase the availability of trials for patients. 

I also want to say a word about inequality of access and thinking about accessing some different ethnicity, so often non-white MPN patients are under-represented in clinical trials, and I know that a focus in the UK and also in North America as well. And it is really important that patients have access to a clinical trial if they need it, and also that we understand how investigational products will work in people of different backgrounds. So for example, we know that probably, Nicole, your blood count assuming it’s a healthy, normal blood count may well be different from mine for background, racial genetic differences, so drug metabolism might be different, so this is really important, and we need to work hard as a community, the clinical community and the patient community to raise awareness and improve access for patients. 

Dr. Nicole Rochester: 

Well, as someone who does a lot of work in health equity, Dr. Harrison, I really appreciate you pointing that out. It’s certainly an issue here in the United States, as you mentioned, differential access to clinical trials, and we’ve learned that not only our patients, often not aware, but often the providers, at least here in the U.S., are not offering clinical trials as an option for patients from marginalized and minoritized communities. So I really appreciate you bringing that up. 

How Can MPN Patients Stay Up to Date With New Treatments?

How Can MPN Patients Stay Up to Date With New Treatments? from Patient Empowerment Network on Vimeo.

What are some ways for MPN patients to stay updated on new treatments? MPN expert Dr. Claire Harrison from Guy’s and St. Thomas’ Hospital in London shares resources for MPN treatment news and the benefits that data sharing brings for all MPN patients.

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Transcript:

Dr. Nicole Rochester: 

Dr. Harrison, how can patients best keep up with the new treatments and communicate with their doctors in a way that makes sure that they have access to these new therapies?

Dr. Claire Harrison: 

Well, I think patient advocacy groups are really important here, and use of social media and the Internet, you’re only a few clicks away from updated data, programs like these, but you also have to trust your team and trust your doctor. We all have to keep up to date. That is a professional requirement, and we also are all networked, so I’d probably get 10 to 15 emails a day from colleague saying, “Hi Claire, can I talk to you about this?” There was an email just the other day about a patient in Washington, actually a very young child, we are all connected. 

We all want the best for our patients. But do you remember that you can contribute as a patient to advance this in your field, and I know many patients are really interested in this, if you are asked to submit in a blood sample, giving permission for us to use your data. So if we can touch maybe on the field of real-world data and real-world data collection here would be good, so what on the real world data? What does that mean? And so this is becoming a really important way that’s recognized by the FDA and other approval agencies in the world, so in Europe, we have EMEA, for example, and in the UK, we have NHRA as a way of collecting data on agents, so once they are approved, we collect data with regard to how the patients do. 

We’ve traditionally done this, but increasingly, as we use electronic data for our patients, we’re more able to collect real-world data, how does my patient who is with myelofibrosis on ruxolitinib (Jakafi) in my clinic inside East London do? So if we can pull that data, we learn a lot more about how these agents are working in patients outside of clinical trial, so you will be contributing if you allow us to collect that kind of data, we discovered JAK2 mutations, CALR mutations, etcetera from samples collected from patients and data. If you want to be part of a clinical trial, then by all means, ask your healthcare team, many MPN centers have lists of trials, and you can always look at clinicaltrials.gov, but boy you throw up a lot of different options when you search in that…on that website. 

Dr. Nicole Rochester: 

Thank you. I think it’s important to talk about real-world data because in this day and age, many of us are very protective about our personal health information and we should be, but as you stated, having access to that data is really a key way to advance the science and technology in the treatment of some of these conditions, so I really appreciate you sharing that.

Dr. Claire Harrison: 

I think just to point out, and I’m sure the audience is acutely aware of what did we learn about COVID? We learned an awful lot about COVID from real-world data from all you MPN patients who gave samples, who told us about how you did with COVID, that’s how we learned about what happened to patients during COVID with MPN, how they responded to vaccination, etcetera. It’s really powerful. And your data will be anonymized, it won’t be linked back to you, Nicole Rochester, or me, Claire Harrison it will be completely anonymous. 

How Can I Get the Best Myeloproliferative Neoplasm (MPN) Care?

How Can I Get the Best Myeloproliferative Neoplasm (MPN) Care? from Patient Empowerment Network on Vimeo.

 There are many exciting developments in the myeloproliferative neoplasms (MPNs) research pipeline, but how can patients get the best possible MPN care? Internationally respected MPN expert Dr. Claire Harrison from Guy’s and St. Thomas’ Hospital in London shares information about research updates, treatment strategies, clinical trials, and how to achieve patient-centered care for you or your loved one.

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Transcript:

Dr. Nicole Rochester:

Hello and welcome. My name is Dr. Nicole Rochester, I’m a pediatrician and a professional health advocate, and your host for today’s Patient Empowerment Network program. We are thrilled that you have decided to tune in. With so many exciting developments in the research pipeline from myeloproliferative neoplasms or MPNs. We’re going to answer several important questions during today’s program, how can you as a patient access the best possible MPN care? Will there be alternative treatment strategies for MPN patients who have failed previous therapies? Should you consider a clinical trial as a path to enhancing your care? Whether you’re living with polycythemia vera, essential thrombocythemia or myelofibrosis, we have so much to unpack and we are joined by world-renowned and highly respected MPN expert, Dr. Claire Harrison. Thank you so much for joining us, Dr. Harrison, it’s an honor and a privilege to join with you.

Dr. Claire Harrison:

It’s a great pleasure and it’s a privilege to join you as well.

Dr. Nicole Rochester:

Following this program, you will receive a survey and we’d be delighted if you take some time to provide your feedback that helps inform future MPN programs that we produce. Please remember that this program is not a substitute for seeking medical care, so please be sure to connect with your healthcare team to determine what is best for you. Now, let’s dive right into this very important topic, how can you get the best myeloproliferative neoplasm care. 

Dr. Harrison, we know that the treatment landscape for MPN is rapidly changing and keeping up with the pace of the developments can be challenging both for healthcare professionals and certainly for patients and their families, so I was wondering if you can give us a general overview of the treatment landscape and maybe highlight anything that’s new and in development that you think would be helpful for the audience.

Dr. Claire Harrison:

Well, sure, I think this is obviously really interesting, very important. It’s a fast-moving field. And one of the first changes actually completely hot off the press is a brand new diagnostic criteria that has been produced by two separate groups that are shortly about to be published, kind of just seeing pre-published and those of us that have been privileged to be involved, have seen them. So that’s gonna really focus the mind of clinicians on how do we achieve the diagnosis, and that’s the first thing that’s really important, get an accurate diagnosis, don’t just accept well, you’ve got an MPN, actually, it’s really important to know what type you’ve got. 

Maybe as much do you tell as possible in terms of the genetic mutation or change that underlies the disease, because that is increasingly important in what we call prognostication, understanding what the risk of events happening due to the disease actually is. When we make a diagnosis, we sometimes can’t be accurate and we might have to go back and revisit them, so some patients don’t get a PV, ET or MF diagnosis, they might get an MPN unclassified. That’s okay, but it’s important to keep revisiting that.

Once we’ve made a diagnosis, then it’s really important to think about what the risk is to the patient, and we’ve had some changes to our risk classifications recently, right from the ET end of the spectrum where we’re thinking more and more actually, those patients who are under the age of 60 with a lower count and the CALR mutation, do we even need to give you aspirin because we might be increasing the risk of bleeding. 

To the other end of the spectrum for patients with myelofibrosis, a more aggressive disease, we want to know more about your mutational profile, so we’re doing more powerful genomic tests and assessing them, your prognosis, and then what the features of your disease are that need treatment. And there are lots of changes, which I think we’ll get into later in our conversation here and lots of new options, which are really important, I just also don’t to leave this segment without saying to all of you who are listening, it’s important that you understand your disease, it’s important that you understand the diagnosis, prognosis, etcetera, and you get the best care.

But that’s maybe not enough, you need to know that you’re taking good care of you, and that’s something that’s really important to all of us, so you need to know that you’re managing your vascular risk don’t just think about your blood. Think about the fact that you know if you’re smoking, quit smoking, if you’re drinking too much, cut it down, if you’re not walking enough,  walk more, lose weight. The majority of patients with MPN actually have a problem with a blood clot, not a further complication of their disease, so maybe we’ll stop there and then we can dive in a bit more deeply

Dr. Nicole Rochester:

Thank you, I appreciate you pointing out the changes with the diagnosis. I’m really excited to learn more about that, and also pointing out the importance of self-care and some of the other risk factors that individuals with MPN can mitigate. So I think that’s extremely important. Can you share a little about what’s in the robust pipeline of potential therapies for patients with MPN, what is it that you’re excited about? And is the future bright in this area?

Dr. Claire Harrison:

I think the future is really bright from the point of view of de-escalating treatment as well as newer treatment, so I think it’s important to point that because all treatments have potential complications inside of it, so as we understand that some of these conditions may have very low risk for patients, it’s important to understand that, and de-intensify, I call that calreticulin (post ET?), I would also call out ET, essential thrombocythemia, which lacks a known driver mutation, so-called triple-negative ET, emerging data suggests that may have very low risk for patients, but what you all want to hear about, of course, is what’s new treatment-wise. So I think just to call out, I’m really excited that there will be a new trial this year for ET patients with Bomedemstat, which is an LSD-1 inhibitor, new target, new molecule. We’ve been testing it in myelofibrosis and we’ve tested it now in a bunch of patients with ET, and it seems to be very efficiently reducing the platelet count not affecting hemoglobin and patients appear to get a good benefit with regard to fatigue, which we know is the number one symptom for patients with MPN, so I’m excited about that because it’s been a long time since we’ve had a new treatment for patients with ET. And then for patients with PV, increasingly across the globe, the availability of this newer formulation of interferon, Besremi is becoming more available and the latest data with that agent suggests that it may be superior to standard therapy such as hydroxyurea, hydroxycarbamide in terms of clotting, et cetera, is really important.

Interestingly, and we may both have to think back to our med school days on this, we’ve been targeting the iron pathway in for patients with PV. So I always tell my patients with PV, do not let anyone give you iron tablets without speaking to one of our team because that’s like putting oxygen on the fire, it’s like feeding the red cell production. So there is a new agent called Rusfertide PTG-300, which targets the iron pathway and allows iron to build up in the body, but it doesn’t allow it to get to the bone marrow and so, this is a new treatment for PV patients, which might reduce the need for iron removal by phlebotomy or venesection, and has been also shown to give symptomatic benefit, and then of course, there’s a bunch of new treatments for patients with myelofibrosis, that’s probably the busiest part of the portfolio at the moment. 

We’ve just seen positive data with me Momelotinib, which is one of the fourth JAK inhibitors, very strong data from the momentum study, good results in patients even with low platelet counts down to 25, and then I’m really excited to see strong data coming with Navitoclax and Pelabresib, which are other agents targeted at are the pathways in myelofibrosis and then finally, in Denmark, they’ve been looking at vaccination strategies, and I know my patients are really interested in vaccination and (inaudible). I don’t have anything new to say (inaudible), but I do have something new to say on vaccination.

So in Denmark, they’ve been looking at producing a vaccination against the calreticulin mutation Nicole, because it’s expressed on the surface of the blood cells, so antibodies can find it. So this is ongoing, no positive result as yet, but it’s still ongoing and there are newer taking off with regards to vaccination structures, and I think that’s really exciting.

Dr. Nicole Rochester:

Wow, there is a lot on the horizon for MPN patients. That is extremely exciting, Dr. Harrison, how can patients best keep up with the new treatments and communicate with their doctors in a way that makes sure that they have access to these new therapies?

Dr. Claire Harrison:

Well, I think patient advocacy groups are really important here, and use of social media and the internet, you’re only a few clicks away from updated data, programs like these, but you also have to trust your team and trust your doctor. We all have to keep up to date. That is a professional requirement, and we also are all networked, so I’d probably get 10-15 emails a day from colleagues saying, Hi Claire, can I talk to you about this? There was an email just the other day about a patient in Washington, actually a very young child, we are all connected. 

We all want the best for our patients. But do you remember that you can contribute as a patient to advance this in your field, and I know many patients are really interested in this, if you are asked to submitting a blood sample, giving permission for us to use your data. So if we can touch maybe on the field of real world data and real-world data collection here would be good, so what about the real world data? What does that mean? And so this is becoming a really important way that’s recognized by the FDA and other approval agencies in the world, so in Europe, we have EMEA for example, and in the UK, we have NHRA as a way of collecting data on agents, so once they are approved, we collect data with regard to how the patients do. 

We’ve traditionally done this, but increasingly, as we use electronic data for our patients, we’re more able to collect real-world data, how does my patient who is with myelofibrosis on Ruxolitinib in my clinic inside East London do. So if we can pull that data, we learn a lot more about how these agents are working in patients outside of clinical trial, so you will be contributing if you allow us to collect that kind of data, we discovered JAK2 mutations, CALR mutations, etcetera from samples collected from patients and data. If you want to be part of a clinical trial, then by all means, ask your healthcare team, many MPN centers have lists of trials, and you can always look at clinicaltrials.gov, but boy you throw up a lot of different options when you search in that… On that website.

Dr. Nicole Rochester:

Thank you. I think it’s important to talk about real-world data because in this day and age, many of us are very protective about our personal health information and we should be, but as you stated, having access to that data is really a key way to advance the science and technology in the treatment of some of these conditions, so I really appreciate you sharing that.

Dr. Claire Harrison:

I think just to point out, and I’m sure the audience is acutely aware of what we learn about COVID? We learned an awful lot about COVID from real-world data from all you MPN patients who gave samples, who told us about how you did with COVID, that’s how we learned about what happened to patients during covid with MPN, how they responded to vaccination, etcetera. It’s really powerful. And your data will be anonymized, it won’t be linked back to you, Nicole Rochester, or me, Claire Harrison it will be completely anonymous.

Dr. Nicole Rochester:

Absolutely, thanks for clarifying that. I want to go back to treatment strategies, you’ve mentioned earlier about low-risk versus high-risk patients, and that some of those criteria are changing. How are treatment strategies changing for low-risk and high-risk patients with MPN?

Dr. Claire Harrison:

It’s complicated because we need to think across the entities, and we don’t have an answer to that for patients with MPN unclassified and we don’t actually have a good answer to that for this entity called pre-fibrotic myelofibrosis which does appear and is strongly recognized in the new diagnostic criteria, but for ET, for example, low-risk patients I mentioned triple negative, calreticulin, m-positive, young patients, platelets less than 1500, not too much changing their queries about aspirin or not, and then for PV patients, we haven’t really changed all kind of high-risk criteria and for both ET and PV, the questionnaire is, should we use the treatment above aspirin or above aspirin (inaudible). And for the most part, that would be hydroxycarbamide, hydroxyurea, which is the commonest treatment used worldwide or Interferon, and these are the right treatment for some patients and not the right treatment for other patients, so some patients can be very fixated on interferon is the absolute best, but there is no clear evidence of that, and there are some patients who interferon is not the right treatment, but low versus high risk becomes even more important for myelofibrosis patients.

And here, we’re thinking about using a risky strategy like transplantation for those patients who have higher risk disease, and we’re using, as I mentioned to you, these molecular markers and newer prognostic tools to stratify patients, and it is important to remember is a patient leave if someone puts your data into a prognostic tool and that comes up with five years, but it doesn’t mean to say five years on the dot your times up, that’s an average. 

And if we put your data into a slightly different tool, we might get something else. So for the most part, we make decisions like transplants,  we are learning more about transplantation and outcomes from that, and then in some countries, some treatments are used for patients who fall into intermediate or high-risk categories, and some clinical trials are based on that as well. I would want to say about myelofibrosis, and something I think I would really like to see changed, not changing yet, but changed, is that we should be able to intervene for patients with a low-risk disease. If my myelofibrosis patients have breast cancer, we would not be going there, then you’ve got low-risk disease we’ll put you on watch and wait, watch and wait is really hard for our patients, we know that I can see you nodding.

Dr. Claire Harrison:

You know that too, right? So if these were patients with breast cancer we would not say, We’ll just watch and wait. So I would really like to see in the next five to 10 years a treatment that we could use earlier in the disease course, but there is nothing at the moment, but we’re looking at that. The other thing we’re looking at, if we’ve got a minute or so is the different endpoint, so we’re trying to understand what does it mean if you’re a (?), so the amount of abnormal genes you’ve got goes down, the amount of bone marrow fibrosis you’ve got goes down. And again, this is something we’ll collect in a clinical trial, but also from real-world data.

Dr. Nicole Rochester:

Wonderful. Wow, thank you. What about for patients who have failed therapies, are there any treatment strategies for MPN patients who have failed traditional therapies?

Dr. Claire Harrison:

Yes, in fact, actually, that’s where we’re evaluating new therapies across all of these entities, so if you’re a PV or an ET patient and you failed a therapy, then this is where, for example, in ET, we would be looking at Bomedemstat or we’re looking at the bromodomain inhibitor Pelabresib, and there’ll be other agents that we’ll be looking at, or we might be looking at vaccination. And for MF patients that while there are a bunch of different therapies for patients who you have not tolerated or progressed through standard therapy. So actually, there’s a lot of options, some of them are already approved and some of them are in clinical trials.

Dr. Nicole Rochester:

And you mentioned clinical trials, and so I think this is a perfect opportunity to transition and start to talk more about clinical trials as a treatment option for NPM patients and really focusing on treatment access, what would you say are the unmet needs in access related to MPN and care, specifically as it relates to clinical trials, and what can we do to address those unmet needs?

Dr. Claire Harrison:

Well, I think there is a problem with rare diseases in terms of geographical access to trials, and we often find patients have to travel a long way. I know that’s true in North America as well as in Europe. And we’re very lucky in our geographical locations, but in some parts of the world, some companies or doing not open clinical trials, so I think there’s an access issue. I think also there is something about patients have to meet rigid entry criteria for clinical trials, and so oftentimes in myelofibrosis, for example, commonly patients who fail (?) have a lower platelet count, and that is often an exclusion criteria. Those criteria are there to try to get a uniform population of patients in a trial, but it can feel like you’re excluded as a patient, and it can feel very tough and for your health care team that we can’t include you in a clinical trial. We also have to remember that it is there for safety purposes, so if there is a lower limit for platelet count that’s often because the drug might affect platelet count. It is really important that we have a broad spectrum of trials available and that we try to increase the availability of trials for patients. 

I also want to say a word about inequality of access and thinking about accessing some different ethnicity, so often non-white and patients are under-represented in clinical trials, and I know that a focus in the UK and also in North America as well. And it is really important that patients have access to a clinical trial if they need it, and also that we understand how investigational products will work in people of different backgrounds. So for example, we know that probably Nicole, your blood count assuming it’s a healthy, normal blood count may well be different from mine for background, racial genetic differences, so drug metabolism might be different, so this is really important and we need to work hard as a community, the clinical community and the patient community to raise awareness and improve access for patients.

Dr. Nicole Rochester:

Well, as someone who does a lot of work in health equity, Dr. Harrison, I really appreciate you pointing that out. It’s certainly an issue here in the United States, as you mentioned, differential access to clinical trials, and we’ve learned that not only our patients, often not aware, but often the providers, at least here in the US, are not offering clinical trials as an option for patients from marginalized and minoritized communities. So I really appreciate you bringing that up. It’s said that clinical trials are tomorrow’s medicine today, and you’ve already kind of alluded to the importance of clinical trials as it relates to MPN. What would you say to an MPN patient who is on the fence or may be concerned or afraid of participating in a clinical trial?

Dr. Claire Harrison:

It’s right to be cautious and you know, careful because ultimately it’s a huge privilege as a clinician that involves patients in clinical trials that my patients trust me and trust my team to look after them with something that is experimental, but remember there are varying degrees of experimental most clinical trials are not first in man, you’re not a complete gene page, it may be a drug, for example, Levetoclax (?) is in clinical trials mainly for myelofibrosis also ET and PV but that is a drug that has been used for thousands of patients, for another indication so talk to your healthcare team, if you don’t find the answer from the primary person that you’re used to dealing with, find someone else, be linked to somebody you trust and that you have a good relationship with, take someone with you to the consultation, write down the questions I’m so sure you say this all the time, don’t you Nicole to the people that you talk to, but write down your questions, don’t be afraid to ask them again, there is no stupid question in this context, you will be given a 30-plus page booklet to read, and I lost count of the number of times, my patients go, yeah, I’ve got this or I trust you.

Actually, you know, you need to read it… We are experimenting on you, and you need to read that and understand. And you need to understand, what happens if I go on the control arm, will I be able to cross over? How many visits will I have, will, I have to pay for those visits, etcetera. It’s all really important, but ultimately the relationship with your healthcare provider is important and using an advocate (inaudible) is really important.

Dr. Nicole Rochester:

I agree, 100%. So important, these are things that I talk about all the time, so I really appreciate that you highlighted that, and just the importance of patients taking an active role in their medical care and also the trust that is required between the patient and their treating providers. So I really appreciate that. Do you have any examples, Dr. Harrison in your own practice of successes with MPN patients who have participated in clinical trials? 

Dr. Claire Harrison:

Oh yes, I think I started doing clinical trials, well golly a long time ago. I think my first clinical trial, we probably the records of written parchment to be honest, but we’ve still learned a lot from that, so that was an ET study. It was from that study we understood about the JAK2 mutation on and we understood how patients behave differently. I think probably the most gratifying thing for me was being involved in the JAK inhibitor studies in myelofibrosis and being involved in delivering Ruxolitinib and Jakafi to patients and seeing the benefits for those patients. 

Big things, you know, there are patients who are alive because they took part in that trial today, I think, but there are also patients for whom small things were also really important, so as a patient, that’s important to define what is the benefit you want to get. So one of my first patients, you haven’t been able to have a bath or a shower for years, because he had terrible what we call aquagenic pruritus itching induced by contact with water, we called him two days after he started Ruxolitinib and he was in tears, he could take… Or you can take it out.

These things are really important. Like myself, I can imagine not being able to dig it out, I would either be very tough for another patient, it was, Well, I looked really skinny because I’d lost loads of weight and I put weight on, and body image was really important as well, but then the small things like being able to be… participate more in family activities is really, really important too.

Dr. Nicole Rochester:

Wonderful, so what advice would you give for patients so that they can really take a proactive approach to their healthcare and feel more confident in talking about their concerns and communicating with their healthcare team, you’ve shared with us how important that is. Do you have maybe two or three specific tips or maybe questions that every MPN patient should ask their healthcare provider?

Dr. Claire Harrison:

I think the first thing to say is, in my personal view is you do not have to be under an MPN expert to get the best care. I know some people differ with regard to that, but these are chronic conditions, there are national and international guidelines, clinicians are connected. We all talk about patients over time, as we like to do that, we like to get the best for our patients, so a local center with a clinician who you trust, who you get on with… Where you can get there easily. You trust their team, you know their logistics work for you, maybe it’s a nurse who work who you get on with, well, who comes to the appointment with you, that is just as good as being under the best professor in the state, where you might not actually see them  when you turn up and go to the unit, so that’s really important, understanding your condition, and if you don’t understand being empowered to ask questions, and if you’re in a position where you can’t ask a question, something’s wrong. So don’t be afraid, take somebody with you, write it down. Sometimes it can be a mistake to do a troll on the internet, so I wouldn’t always encourage that because what’s on the internet is not always accurate, but go to a trusted website as the clinician… Where can I go to find out more information? Some patient advocacy groups run buddy systems that can also be very helpful and it can be very empowering to meet another patient with the same or similar condition, so I think those are all helpful tips from my perspective, also don’t expect to get all the answers all the time, it can be really tricky as a clinician, maybe you get a patient who comes with a big long list of questions, and say What is your top question that you really want answers to.

Dr. Nicole Rochester:

Those are awesome, awesome tips. I’m just gonna repeat a few of them, just to highlight, you mentioned prioritizing your concerns which is incredibly important, and acknowledging that the clinician doesn’t have unlimited time, and so really focusing on the things that concern you the most, you mentioned bringing a buddy to appointments, which is something I fully endorse, so that there’s someone else that’s taking notes or… It can be your eyes and ears during that appointment, things that you may have missed either because of anxiety or stress, and you mentioned writing things down, taking notes, even as the patient asking questions, which is so incredibly important, and really the way that I feel patients demonstrate their involvement in their disease and being an active member of the team, so I really, really appreciate those tips, Dr. Harrison, I think that you have given us so information, so much information about how to empower MPN patients and their families so that they can really get the best care at the outset. So it’s time to wrap things up, Dr. Harrison, I’d love to close with any closing thoughts that you have, any takeaway messages you’ve given us so many already, but if there’s anything else that you have not had the opportunity to share with the audience, I love for you to go ahead and do that now.

Specifically anything related to how they can advocate for themselves or any other important messages that you wanna leave the audience with.

Dr. Claire Harrison:

I think I would want the listeners to feel empowered and to feel very hopeful, this is the time where there’s a great change. We’ve been through a really difficult couple of years, but actually, we group together really well as a patient in a clinical community, and we’ve learned a lot, so trust your clinical team if you don’t trust them if there’s a problem. Move on. And don’t be afraid to do that, don’t be afraid to ask for another opinion, actually, we as clinicians like somebody else to give an opinion on our patients, that’s another thing we haven’t covered, and do connect with patient advocacy and keep up-to-date. Do you ask for a copy of your letter, don’t be afraid to ask for copies of your diagnostic information, you will properly outlive the relationship with your clinician. I will probably retire before my patients move on from my practice, so keep the information and understand it as much as you can.

Dr. Nicole Rochester:

Wonderful, thank you. So Dr. Harrison and you’ve just left us with a message of hope and a message of empowerment, and I think those two things are incredibly important, so I really appreciate you taking time with us today, and thank you so much for sharing your insights and your expertise. And I wanna thank you all for tuning in to this Patient Empowerment Network program. 

Notable New MPN Treatments

Notable New MPN Treatments from Patient Empowerment Network on Vimeo

What’s the latest in myeloproliferative neoplasm (MPN) treatments? Dr. Kristen Pettit from Rogel Cancer Center gives updates about treatment developments for myelofibrosis, polycythemia vera (PV), and essential thrombocythemia (ET) care including JAK inhibitors, BCL-2 inhibitors, BCL-XL inhibitors, BET inhibitors, and others.

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Transcript:

Dr. Kristen Pettit:

There are so many new treatments in MPNs that I’m excited about, so one that is investigational that has been moving through the pipeline is momelotonib, which is a newer JAK inhibitor for patients with myelofibrosis. The mechanism of action is slightly different than the other JAK inhibitors, ruxolitinib (Jakafi), baricitinib (Olumiant), and pacritinib that’s improved as well.

The hope with momelotonib is that it will do some of the good things that the other JAK inhibitors do reduce symptoms and reduce spleen size, but also potentially improve anemia for patients who struggle with anemia, which is such a high proportion of our patients with myelofibrosis. I think that’s one exciting thing, another exciting avenue are new potential up-front treatment strategies that are being studied, so there are a number of different clinical trials going on right now, testing the strategy of either standard ruxolitinib or Jakafi by itself compared head-to-head versus a combination of Jakafi plus another medication.

Those other medications that are being tested in trials include the BET inhibitor called parsaclisib, also BCL-2, BCL-XL inhibitor called navitoclax, and a Pi3 Kinase inhibitor called parsaclisib. These upfront head-to-head treatment strategies are going to be very important to keep an eye out for over the next couple of years. The hope is that these combination strategies could deepen responses and potentially prolong responses when a new drug is combined with the JAK inhibitor as the first treatment option for patients with myelofibrosis. In the later line setting, one thing that’s exciting is Imetelstat, which is a telomerase inhibitor.

This is the first study in my myelofibrosis that is trying to specifically prove whether or not it is linked in survival for patients with myelofibrosis. So, I think that’s very exciting and something to keep an eye out for.

In polycythemia vera, one newer treatment option that’s getting a lot of excitement is the Hepcidin mimetic called rusfertide, this medication will hopefully harness the body’s iron metabolism pathway and act as sort of a chemical phlebotomy as opposed to an actual therapeutic phlebotomy in order to control the hemoglobin and hematocrit for patients with PV as well as improve symptoms.

In ET the newer agents that are being investigated include the BET inhibitor parsaclisib, is also being studied for myelofibrosis as well as an LSD-1 inhibitor called bomedemstat. Both of these look exciting so far, as far as their ability to both control platelet count and improve symptoms for patients with ET.

An MPN Expert Defines Clinical Trial Types

An MPN Expert Defines Clinical Trial Types from Patient Empowerment Network on Vimeo.

 What are the types of clinical trials? Dr. Ruben Mesa explains the differences and discusses what patients should expect with each type.

Dr. Ruben Mesa is an international expert in the research and care of patients with myeloproliferative neoplasms (MPNs). He serves as executive director of UT Health San Antonio MD Anderson Cancer Center in San Antonio, Texas. More about this expert, here.

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Transcript:

Katherine:                  

You touched upon the various types of clinical trials and I would like to look at each one of them individually. So, let’s start with the double-blind clinical trial. What is that?

Dr. Mesa:                   

What that refers to is that neither the patient nor the physician knows which of the two comparator arms of the trial are more that a patient receives. So, with a trial, let’s say that there’s more than one way that someone can be treated. Let’s say arm A is drug X, and arm B is drug X plus drug Y, where drug Y is the experimental drug, and drug X is our standard of care. The reason they are double-blinded is that if the physician or the patient know exactly which arm they’re on, that might have an influence in terms of the physician assessing the response of the patient, the patient filling out questionnaires regarding response in symptoms.

It’s natural for us if we’re on a drug to say, “Oh, wow, you know, I automatically feel better. I’m excited about being on this,” and lead to what we call a bit of a placebo effect. Where there have been studies in the past where someone got a placebo but believed they were already feeling better even though nothing different had occurred. So, that they had somewhat kind of convinced themselves they were going to be doing better. So, the intent is, again, just to get the most objective set of response both from the physician and from the patient.

Katherine:                  

What is a randomized clinical trial?

Dr. Mesa:                   

A randomized trial means that when there is more than one arm, which treatment that a patient receives is random, is not chosen by the physician. Why that is the case is, again, we truly want to see which approach is better.

If the physician got to choose, they may inadvertently put all the sicker patients on one arm, or put all the less sick patients on one arm. In either case, it would make the value of the clinical trial less.

The value of the clinical trial, the entire reason we do them, is to try to, in the best way that we can, figure out which approach was better, whether that’s a treatment for your MPN, whether that’s figuring out whether a COVID vaccine helps to prevent to COVID, whether it’s figuring out whether a cholesterol lowering medicine is a good medicine to be on. Regardless of the reason, we want to know, is it the right way to go?

Because after that, there will be a lot of people who receive that treatment.

Katherine:                  

And finally, what is a controlled clinical trial?

Dr. Mesa:                   

A controlled clinical trial is, again – is following these same pieces where it has a comparator, where that comparator arm is sometimes also called the control, meaning that’s kind of the baseline – and, again, you’re looking to see, does that make a difference a baseline. So, let me use an MPN analogy. When ruxolitinib or Jakafi was first tested, there were no approved drugs for myelofibrosis.

So, how that worked – it was a controlled study. There was randomized placebo control. Half the group got ruxolitinib, half got placebo. After 24 weeks, people could then go on to get the ruxolitinib.

So, everyone eventually got the ruxolitinib. But, for those 24 weeks, we were able to compare what did the standard of care, which was really nothing, against ruxolitinib and saw a dramatic benefit. Now, the newer trials, now that ruxolitinib (Jakafi) is approved, ruxolitinib has been the control.

So, when there was a ruxolitinib and momelotinib trial to see if momelotinib was an effective drug, it was compared against ruxolitinib. Now, it was blinded, so that you didn’t know which of the two that you were on, but people were getting an active control. So, that is an active-controlled trial versus a placebo-controlled trial where the comparator is placebo.

Katherine:                  

What is an observational study, and how does that differ from the other clinical trials?

Dr. Mesa:                   

An observational study, as the name might suggest, is, again, where you’re observing a group of individuals, whether they start on a treatment, whether you’re trying to see how the disease behaves over a period of time.

But what it typically does not do is that you are intervening in a very specific sort of way where you are again changing how people otherwise would have been treated.

Clinical Trials As an MPN Treatment Option: What You Should Know

Clinical Trials As an MPN Treatment Option: What You Should Know from Patient Empowerment Network on Vimeo.

 Should you consider an MPN clinical trial? Dr. Ruben Mesa provides an overview of clinical trials—including the phases—and defines common trial terms and types. Dr. Mesa shares advice on trial participation and gives an update on the latest advances in MPN research.

Dr. Ruben Mesa is an international expert in the research and care of patients with myeloproliferative neoplasms (MPNs). He serves as executive director of UT Health San Antonio MD Anderson Cancer Center in San Antonio, Texas. More about this expert, here.

Download Guide

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How Treatment Goals Impact MPN Treatment Decisions


Transcript:

Katherine:                  

Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today, we’re going to discuss research advances in myeloproliferative neoplasms, or MPNs, and review key information that patients should know about clinical trial participation.

Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining me is Dr. Ruben Mesa. Dr. Mesa, welcome. Would you please introduce yourself?

Dr. Mesa:                   

Thank you so much. It’s a pleasure to be here. I’m Ruben Mesa. I’m the executive director of the Mays Cancer Center at UT Health San Antonio MD Anderson.

Katherine:                  

Great. Thank you so much for joining us today. As we move through this conversation, we’ll talk about the classic myeloproliferative neoplasms, essential thrombocythemia, polycythemia vera, and myelofibrosis. So, before we dive deeper into our clinical trial discussion, let’s talk about research advances. What are the latest developments in the field of myeloproliferative neoplasms?

Dr. Mesa:                   

There are many advances that are very important for patients to know about. First, we’re learning more about the biology of these diseases. Why do they occur? Why do they progress? Why are they different in different individuals? Indeed, the course of these diseases can be quite variable. So, these important pieces of biology are important for us to be able to better diagnose the disease, monitor the disease, and develop better therapies.

Second, I would say that there are many important new therapies that are in development. They are only able to be developed into therapies that patients can use by the process of undergoing through clinical trials. But these therapies are for patients with essential thrombocythemia, polycythemia vera, and myelofibrosis. So, a critical part, but many different scientific advances that are important and hopefully will have an important impact for patients with MPNs.

Katherine:                  

Mm-hmm. It sounds very promising. And, of course, these research advances wouldn’t be possible without patients actually participating in clinical trials. So, can you help us understand more about the trials? What is a clinical trial? Let’s start with that.

Dr. Mesa:                   

It’s a very good question. A clinical trial is a very structured way for us to be able to ask a question, whether that question is, is a new therapy safe?

Is it effective for a particular disease? Sometimes there are clinical trials that don’t involve treatments, that involve questionnaires, or other interventions, things like exercise or yoga or other things. But in general, it’s where we are having a patient do something in a structured way that we are able to then assess. Is it safe and is it effective? Is it reaching our goal in terms of trying to have an impact on that disease, whatever that is?

So, if it’s a blood pressure medicine, it’s probably about lowering the blood pressure. If it was about the COVID vaccines, did the vaccines help people from developing COVID or make COVID less severe? So, what they’re testing is variable. But the concept is the same.

It’s a very organized way for patients to be able to receive something that is closely monitored, that has been approved in advance as being a reasonable, safe, and ethical to ask patients to participate.

Katherine:                  

What are the phases of clinical trials?

Dr. Mesa:                   

So, the phases are particularly to treatment or drug use trials for developing new therapies. And they start with Phase I, which is typically the first time a drug is tested in human beings. It’s already gone testing in the lab to see whether it should work. It likely has had some animal testing to get a sense of dose and safety. But then, the first individuals who receive the drug, it’s on Phase I. What we’re really trying to understand the safety of the drug and to try to get around the dose.

There is the Phase II, typically where we’re testing a therapy in a group of people that are all similar to see what is the effectiveness of the treatment.

So, that first phase is, is the drug safe? What is the dose? The second phase is, is the drug effective? and however we define effective for that particular disease. And then, the third phase is where that new treatment is compared against how we otherwise normally would have treated the disease. So, if that’s in the setting of where we already have a drug that is approved, it’ll be compared against that drug.

If there’s never been a drug, then that comparator could possibly be a placebo, or an inactive part, or observation, or sometimes best alternative therapy the doctors can use.

There is, finally, a fourth phase. There are times that, after a drug is approved, the FDA will ask for additional information – safety information, effectiveness information – even after approval, and that’s something referred to as the fourth phase.

Katherine:                  

Let’s move on to some common language used around clinical trials. I’ll mention a few and then maybe you could define them for the audience. The first one is, informed consent. What does that mean?

Dr. Mesa:                   

Informed consent is that what is involved with participating with a trial, what the drug is, what do we know about its safety, what you might anticipate, either in terms of side effects, whether a likely side effect or a rare side effect.

And what’s involved with you in terms of a participation, whom to call if there’s an issue. It really is an extensive document. It looks like a contract, but actually it is not.

So, informed consent is not an obligation to participate in the trial, nor does it mean that you have to stay on the trial for any length of time.

It is truly to inform you, and then you sign it, saying that you have been informed. One important concept: in the clinical trial, you are always in the driver’s seat, so that if you take – you sign the consent and you choose not to participate, you’re done then and there. If you take one dose and you don’t want to take anymore – fine. So, you’re always in the driver’s seat. It looks like a contract; it clearly is not. It is not an obligation from your side.

Katherine:                  

That’s good to know. What about standard of care?

Dr. Mesa:                   

So, standard of care is the medical language we use to how we would treat you otherwise. So, a clinical trial, by definition, is we’re trying something new.

Sometimes it’s a drug that’s never been approved, but sometimes it’s a drug that’s approved that we’re testing in a different way. Standard of care is kind of the default care that you would normally receive anyway, that is kind of the medical standard for your particular condition.

Katherine:                  

What does adverse event mean?

Dr. Mesa:                   

An adverse event means any possible side effect or event, a hospitalization or something of that nature. And then, the doctor typically attributes whether it’s related or unrelated. So, let me use an example.

If you’re on a clinical trial with a drug, but you go skiing; you fall and you break your ankle. That is an adverse event. You were hospitalized and had a broken ankle during the conduct of the study.

Now, it likely is not attributed to the trial drug, and that’ll be discussed and investigated.

But maybe it was. Maybe you felt light-headed and you passed out because of the drug you were on and you were skiing. So, again, that is a determination that your doctor makes about an adverse event. But it’s an adverse event whether it’s related to the drug or whether it has nothing to do with the drug.

Katherine:                  

And what about HIPAA? What does that mean?

Dr. Mesa:                   

HIPAA relates to – and I forget the full acronym – but really, it’s around the integrity of your patient information and that that is not able to be disclosed in a way that is either harmful to you or to individuals that really are not authorized to receive that information, which typically includes your treating team with permission – if you give permission to another healthcare provider or system, to your insurance company, et cetera.

But it’s really around both portability, I believe, in terms of your patient record, but also in terms of privacy.

Katherine:                  

A big concern for patients who may be considering participating in a clinical trial is fear that they will receive a placebo. Can you define what a placebo is for the audience?

Dr. Mesa:                   

So, a placebo means a drug that is inert. So, historically, a placebo has been, let’s say, like a sugar pill.

So, one, it is a very small minority of trials in this day and age that have a placebo. So, one, it’s almost solely in the setting of a Phase III trial. So, in a Phase I trial, everyone gets the drug. In a Phase II trial, typically everyone gets the drug. In a Phase III trial, there is typically something that it is compared against.

Now, if there’s a standard of care approach, that’s likely the comparison group.

Now, the group that starts with standard of care may well then have a period where they “crossover,” where they are treated in one way for a certain amount of time, and then get kind of the drug in question. A placebo is truly meant to be the same as kind of getting nothing. Now, in a disease like MPN, the number of placebo control trials is really very few. Sometimes a situation that they are used is where the comparator is, let’s say, trying to use two drugs – so, let’s say, the standard of care plus a new drug – versus the standard of care alone.

Now, sometimes people will take both the standard of care and a placebo so that they are, what we call, blinded. So, they don’t know which treatment arm they were on. They’re still getting treatment. They’re still getting the treatment that they would’ve anyway, but they don’t get two treatments. So, the second part is a placebo.

But anything like this, one – any trial a doctor refers you to, one should fully understand exactly how the trial works. Is it a trial with a placebo? Is it not? And then, allow that to help kinda inform your own consideration.

Is this something that I’m willing to do? Does it make sense? Is there a different approach? You know, is there a different trial that does not involve a placebo? So, I think, as physicians, we clearly understand that we try to absolutely minimize the situation where placebos are used. And when they are used, they are only used in a way that we feel that no one is getting less than at least the standard of care therapy that they would otherwise.

You know, it is unethical for there to be a placebo that really would deny patient a therapy that we otherwise know would be helpful.           

Katherine:                  

You touched upon the various types of clinical trials and I would like to look at each one of them individually. So, let’s start with the double-blind clinical trial. What is that?

Dr. Mesa:                   

What that refers to is that neither the patient nor the physician knows which of the two comparator arms of the trial are more that a patient receives. So, with a trial, let’s say that there’s more than one way that someone can be treated. Let’s say arm A is drug X, and arm B is drug X plus drug Y, where drug Y is the experimental drug, and drug X is our standard of care. The reason they are double-blinded is that if the physician or the patient know exactly which arm they’re on, that might have an influence in terms of the physician assessing the response of the patient, the patient filling out questionnaires regarding response in symptoms.

It’s natural for us if we’re on a drug to say, “Oh, wow, you know, I automatically feel better. I’m excited about being on this,” and lead to what we call a bit of a placebo effect. Where there have been studies in the past where someone got a placebo but believed they were already feeling better even though nothing different had occurred. So, that they had somewhat kind of convinced themselves they were going to be doing better. So, the intent is, again, just to get the most objective set of response both from the physician and from the patient.

Katherine:                  

What is a randomized clinical trial?

Dr. Mesa:                   

A randomized trial means that when there is more than one arm, which treatment that a patient receives is random, is not chosen by the physician. Why that is the case is, again, we truly want to see which approach is better.

If the physician got to choose, they may inadvertently put all the sicker patients on one arm, or put all the less sick patients on one arm. In either case, it would make the value of the clinical trial less.

The value of the clinical trial, the entire reason we do them, is to try to, in the best way that we can, figure out which approach was better, whether that’s a treatment for your MPN, whether that’s figuring out whether a COVID vaccine helps to prevent to COVID, whether it’s figuring out whether a cholesterol lowering medicine is a good medicine to be on. Regardless of the reason, we want to know, is it the right way to go?

Because after that, there will be a lot of people who receive that treatment.

Katherine:                  

And finally, what is a controlled clinical trial?

Dr. Mesa:                   

A controlled clinical trial is, again – is following these same pieces where it has a comparator, where that comparator arm is sometimes also called the control, meaning that’s kind of the baseline – and, again, you’re looking to see, does that make a difference a baseline. So, let me use an MPN analogy. When ruxolitinib or Jakafi was first tested, there were no approved drugs for myelofibrosis.

So, how that worked – it was a controlled study. There was randomized placebo control. Half the group got ruxolitinib, half got placebo. After 24 weeks, people could then go on to get the ruxolitinib.

So, everyone eventually got the ruxolitinib. But, for those 24 weeks, we were able to compare what did the standard of care, which was really nothing, against ruxolitinib and saw a dramatic benefit. Now, the newer trials, now that ruxolitinib (Jakafi) is approved, ruxolitinib has been the control.

So, when there was a ruxolitinib and momelotinib trial to see if momelotinib was an effective drug, it was compared against ruxolitinib. Now, it was blinded, so that you didn’t know which of the two that you were on, but people were getting an active control. So, that is an active-controlled trial versus a placebo-controlled trial where the comparator is placebo.

Katherine:                  

What is an observational study, and how does that differ from the other clinical trials?

Dr. Mesa:                   

An observational study, as the name might suggest, is, again, where you’re observing a group of individuals, whether they start on a treatment, whether you’re trying to see how the disease behaves over a period of time.

But what it typically does not do is that you are intervening in a very specific sort of way where you are again changing how people otherwise would have been treated.

Katherine:                  

Are there other common terms that you think patients should understand and know about?

Dr. Mesa:                   

As you relate to adverse events, sometimes you would hear the term, serious adverse event, and this is sometimes to separate whether, again, as the name suggests, they are serious – and by serious, that sometimes has a threshold of requiring hospitalization, requiring a visit to the ED, emergency department – to potentially being life-threatening. Now sometimes these are associated with the disease or the medication. Sometimes, they’re unrelated. But these are ones we’re particularly sensitive of.

Again, as one looks at side effects of therapies, you’ll look at an informed consent and typically it will be a fairly long list of possible things. A relatively short list of things that we expect might happen being likely to occur, maybe can occur in greater than 20 percent of people, and sometimes some really rare things that are less likely to occur. But we also look at – when we look at a trial and look at all of the side effects that people had – were they related, were they unrelated, and were they potentially serious or not?

Katherine:                  

Let’s talk about safety. What are the risks of a clinical trial participation?

Dr. Mesa:                   

So, clinical trials are structured to try to have the safety be front and center in terms of caring for patients.

So, depending upon the therapy and how much is known about that therapy will dictate the frequency in which the patient is observed. If there’s specific side effects, how are we monitoring for those side effects so that, if they are starting to occur, we can discontinue it, discontinue the drug, lower the dose, etc. So, there are some times we do accept as patients and as physicians some potential new side effects in the hope that a therapy might be more effective against the disease.

So, if it might irritate the eye, do we have eyes exams? If it might cause the heart rhythm to be abnormal in some way, do we monitor electrocardiograms? If it might cause rash, do we have exams at a certain frequency to assess for rash? Is there more blood count tests done to assess for changes in the blood counts, irritation in the liver or kidney?

So, depending upon how the drug might impact someone, it really helps to dictate what monitoring is occurring in the conduct of the study to monitor for side effects.

And then there will always be a very specific plan. Well, if a side effect occurs, what do we do? Is the drug stopped? Is the dose lowered? If it’s stopped, how long do we stop it? – usually until that side effect has recovered. And then, do we restart the drug? And, if so, do we restart it at the same dose or at a dose reduction? So, a clinical trial is guided by something that is called a protocol, which is kind of the long recipe book for exactly how that trial will work and will detail all of these things so that it can be done in a thoughtful way, but also in a consistent way, across institutions.

Katherine:                  

Mm-hmm. Well, that leads me to the next question. I’m curious to know what protocols are in place to protect patients?

Dr. Mesa:                   

So, it depends very much by each clinical trial.

There are specific protocols in that any clinical trial that is developed needs to be reviewed and approved at multiple levels through an institutional review board, which is in ethics or specifically focus on clinical trials for an institution or sometimes for a broader group. There are times that there’s additional regulatory oversight from the FDA, from the National Cancer Institute, cooperative groups, and others.

So, there’s really an entire network of things put in place. Mandatory training for physicians, nurses, and staff in terms of good clinical practices in the conduct of the study. There are specific safeguards in terms of the handling of the drugs. The pharmacist, and other safeguards in terms of you receive the drug that you’re intended to receive at the right dose, made in the right way.

Everything is heavily focused in medical practice anyway on patient safety, but you can imagine that in the conduct of a clinical trial that’s taken really to the next level in terms of trying to provide every safeguard for the patient.

Katherine:                  

Dr. Mesa, let’s move on to participation. How can someone find out about what trials are available to them?

Dr. Mesa:                   

So, first and foremost, it begins with a conversation with your physician. And overall, clinical trials – the majority of clinical trials are in situations where things are not going perfectly. You know, if you’re doing well, you’re feeling well, you’re doctors a hundred percent happy with how you’re doing, then a clinical trial may or may not be an option. They are usually in a situation where things are not going as well as we would like. You have residual symptoms; you’ve only had a partial response.

If the current medicines for the disease don’t agree with you, you had side effects, or others. Now additional research for learning about these trials include many different organizations. There are disease-specific ones, like the MPN Research Foundation, MPN advocacy & Education International, MPN Hub, amongst many others. There is the broader, clinicaltrials.gov. Now, that’s a very broad site.

It is searchable. Sometimes it gives you more information than is helpful, but most things are listed on there. The Leukemia and Lymphoma Society, at LLS.org, has a specific kind of navigation function that they have for learning more about clinical trials and getting matched up with them.

But it truly starts with you and your doctor. If things aren’t working well, what are the options that I have? Is it a different option in terms of therapy? Or, if not, asking about clinical trials because clinical trials, again, will have their own upsides and downsides you and doctor will go through depending upon your situation.

Katherine:                  

What are the barriers to accessing clinical trials? Are there any?

Dr. Mesa:                   

So, first, clinical trials have, kind of, the broader logistics barriers. Frequently, you need to enroll and participate at a particular site and sometimes that site is not locally. Your doctor may or may not be participating in that trial. Some trials are only done at a single institution. So, for many, there can be a hassle factor.

You know, it’s impractical for me to be there, or be there for the frequency of visits or other pieces. So, that is one potential barrier. Overall, we hope that insurance or other coverage is not a barrier. In general, clinical trials are structured in a way to hopefully have them be financially neutral for patients.

It’s not less expensive to get your care if you’re on a trial, but it shouldn’t be any more expensive because the standard of care items are billed to your insurance as they would be normally. But if there are things that are experimental, they are included as an expense of running the trial and you’re not charged for those. Now the other barrier is, specifically, trials tend to have a specific set of eligibility for participation that are medical. It may be in a subset of patients based on any number of factors.

And there may be other limiters in terms of prior health conditions, sometimes in terms of age, sometimes in terms of how well the heart, the liver, the kidneys, or other things work. There’s both kind of a logistical piece, but then there is very specific eligibility. As a researcher, when a patient is a candidate for a clinical trial, I will have to go point by point, and sometimes there might be 50 points of disease, blood tests, and organ function – other pieces that need to be correct for participation in that trial.

It’s not to say that drug may not conceivably help that individual. It’s to say that for that specific trial, that’s what’s needed to participate in that very specific clinical trial.

So, sometimes that can lead to a bit of frustration, but it’s critical so that that trial is comparing the right group of patients so that the safety is really as great as the safety can be in the conduct of that study.

Katherine:                  

Right. What sort of questions should patients be asking their healthcare team about participating in a clinical trial?

Dr. Mesa:                   

Well, I think this discussion acts as a nice framework. So first, why should I participate in this clinical trial? Meaning, what is it about my disease that makes a different treatment option a consideration? So, why to begin with? And, if so, why this trial? What drug is it? Why does it help? If it was successful, what can I expect?

Then, what is entailed with me to participate? How frequently do I need to come? What’s involved? Is there more expenses that I can anticipate?

Again, in general, I can hopefully say no. But, of course, if you’re having to fly once a month, that, in some trials, may be covered as an expense of the trial and you’re reimbursed, but it may not. So, again, I think it starts with, medically, why does it make sense? What is involved for me? And then, really, what are those other next steps? And then, what are the alternatives? Sometimes there’s more than one clinical trial as an alternative. Sometimes there’s other options that are not a clinical trial that are an alternative to consider as well.

Katherine:                  

Before we end the program, Dr. Mesa, I’d like to get your thoughts. What message would you like to leave the audience with related to clinical trial participation?

Dr. Mesa:                   

Clinical trials are essential.

They are really the only way that we make progress in terms of developing new treatments. In the United States, less than 10 percent of patients with diseases like MPNs and cancers participate in clinical trials. And, to be honest, this really slows our ability to develop new therapies that would benefit folks. These are a very important resource.

I’ll flip it around another way – in children, where, again, we want to do everything that we can – about 80 to 90 percent of children are treated in the conduct of a clinical trial, where, again, they’re constantly pushing the envelope to try to develop better therapies.

And because of that, I think our progress comparatively, in childhood cancers, has been much faster in developing therapies than it has been in adults. So, it’s critical. It’s an opportunity.

Again, it’s very much a personal decision, but it’s something that I would strongly encourage you to consider. Again, one can begin and you are not obligated to remain on if that clinical does not, in the end, end up having the benefit that you had hoped, or if it ends up having a side effect that you prefer to not experience.

Katherine:                  

Dr. Mesa, thank you so much for joining us today. It’s been a pleasure.

Dr. Mesa:                   

Wonderful. Thank you so much for including me.

Katherine:                  

And thank you to all of our partners. To learn more about MPNs and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us.

Expert Perspective: Hopeful MPN Research and Development

Expert Perspective: Hopeful MPN Research and Development from Patient Empowerment Network on Vimeo.

MPN expert and clinical researcher Dr. Abdulraheem Yacoub shares excitement about the future of MPN treatment and research, including an optimistic outlook for new approvals in the coming year. 

Dr. Abdulraheem Yacoub is a hematologist oncologist at the University of Kansas Cancer Center. Dr. Yacoub is an active researcher and is an Associate Professor of Hematologic Malignancies and Cellular Therapeutics. Learn more about Dr. Yacoub, here.
 
 

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How Treatment Goals Impact MPN Treatment Decisions

How Treatment Goals Impact MPN Treatment Decisions

Advice for Choosing MPN Therapy: What’s Right for You?

Advice for Choosing MPN Therapy: What’s Right for You?

How Should You Participate in MPN Care and Treatment Decisions?

How Should You Participate in MPN Care and Treatment Decisions?


Transcript:

Katherine:

I wanted to get your take on the future of MPN research and treatment. Are there new developments that you’re excited about and that make you hopeful?  

Dr. Yacoub:

Absolutely. So, again, I would like to take the last few minutes to advocate for the future. And the future can only come when doctors and patients and advocates work together to advance the science. We have few tools to treat patients and to help patients. We have a lot of unanswered questions. And the only way to answer them is by designing quality clinical trials, enrolling patients on trials, taking the risk, and trying to find new answers and new therapeutics. So, I always would like to advocate for patients to seek clinical trials whether with their doctor or whether they have to travel for it, and for doctors to consider that for their patients. That’s the only way to advance science.  

There are very important national and international studies going on right now. One of the – and first, I would like to emphasize is that we have had ruxolitinib (Jakafi) as the only therapy, or the first-line therapy for myelofibrosis for a decade now.  

Not everybody responds to it, not everybody responds to it for a long time. So, now we’re designing combination trials. So, there’s a few studies that we are trying to redefine, “Is ruxolitinib alone enough, or should we have a combination first-line therapy?” So, these are some of the more important questions being asked right now.  

And this is definitely one of the bigger moves in the field, is trying to redefine what is the first-line therapy for myelofibrosis. For polycythemia vera, we’re also exploring therapeutics that would reduce phlebotomy with things you can add to your medical care to reduce phlebotomy.  

So, that’s also going on. And it’s definitely a big leap forward for many of our patients. For ET, when we don’t have any actual drugs approved other than hydroxyurea (Hydrea) and anagrelide (Agrylin), we actually have trials with interferon going on.  

So, I would like to advocate for that. So, interferon succeeded and now approved for PV, but not yet for ET. We’re working on that. So, again, in every disease, we’re trying to design clinical trials to redefine what is the best treatment today.  

We’re also doing studies to understand the cancer. So, studies where patients donate their samples for research. These are very helpful, very important. And contributing to that always advances the science, and it’s low effort to the patients. So, if there’s a clinical trial that is offered to patients, I would strongly urge everybody to consider that favorably and contribute to science. 

That’s the only way we can help future patients and ourselves immediately, at moving the field forward.  

What Are the Signs of MPN Progression?

What Are the Signs of MPN Progression? from Patient Empowerment Network on Vimeo.

Dr. Abdulraheem Yacoub, an MPN specialist, explains how essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF) may progress from one disease to the next, including potential signs and symptoms of MPN progression. 

Dr. Abdulraheem Yacoub is a hematologist oncologist at the University of Kansas Cancer Center. Dr. Yacoub is an active researcher and is an Associate Professor of Hematologic Malignancies and Cellular Therapeutics. Learn more about Dr. Yacoub, here.
 

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What Are Treatment Options for Essential Thrombocythemia?

What Are Treatment Options for Essential Thrombocythemia?

What Are Treatment Options for Polycythemia Vera?

What Are Treatment Options for Polycythemia Vera?

What Are Treatment Options for Myelofibrosis?

What Are Treatment Options for Myelofibrosis?


Transcript:

Katherine:

We have a couple of questions from the audience. This one is from Sarah. She writes, “I’ve been living with essential thrombocythemia for three years, and have been relatively stable. Of course, I’m worried about progression to PV or MF. What is my chance of progression, and what are the signs of progression?” 

Dr. Yacoub:

That’s a very good question. And unfortunately, we’re very good at describing those numbers. Unfortunately, our tools at interfering are not as good. So, in general, patients with ET, statistically speaking, have a life expectancy that is not different from their age match peers. And Sarah’s story will be not too indifferent from her sisters and her mother, in terms of what’s going to happen to her long care and her health, provided she gets good medical care. The exception to that is that there is a transformation risk. For ET we caught around a 4 percent every 10 years in which ET will actually change into a different cancer, a higher risk cancer.   

Could be MF, could be MDS, could be acute leukemia. And that will be a much more serious diagnosis. So, it’s about 4 percent in 10 years. We do have a – or we extrapolate some of the data from other cancers. So, certain mutations are more favorable, certain mutations are more risky. And we try to forecast that but worried it’s really hard to predict that since it’s such a long journey with disease. The first symptoms or the findings, when patients start suspecting that their disease has changed, is that the pattern of symptoms that they have are different.   

They often become worse. So, they have more constitutional symptoms, more tiredness, more fevers, more night sweats, losing weight, not being able to eat a full meal, abdominal distension, the spleen gets bigger.  

So, these are some of the feelings that patients can experience that lead to this. Other objective things is when the blood tests change in a less favorable way. So, for patients with ET who always run at 800,000 platelet count, if they’re suddenly 200, and that’s in the normal range, but that’s actually not good news, because the cancer changed. And this change is not favorable. So, as the doctors run routine labs, if they see the sudden change in labs, that’s also abnormal.  

If the doctor can feel that the spleen gets bigger every time, that’s also concerning. If the patients suddenly have anemia or very high white cell count or immature white cells in the blood, that’s also a concern.  

So, that’s why it’s great or important to establish a baseline symptom burden.  A baseline spleen, a baseline bone marrow biopsy with mutation analysis, so that patients have a clear reference point to where they started, and if things change, they can always go back to that point and compare.  

Advice for Choosing MPN Therapy: What’s Right for You?

Advice for Choosing MPN Therapy: What’s Right for You? from Patient Empowerment Network on Vimeo.

MPN specialist Dr. Abdulraheem Yacoub reviews factors that determine which treatment is most appropriate for your essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF). 

Dr. Abdulraheem Yacoub is a hematologist oncologist at the University of Kansas Cancer Center. Dr. Yacoub is an active researcher and is an Associate Professor of Hematologic Malignancies and Cellular Therapeutics. Learn more about Dr. Yacoub, here.
 

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Expert Perspective: Hopeful MPN Research and Development

Expert Perspective: Hopeful MPN Research and Development


Transcript:

Katherine:

As with most conditions, all patients are different, of course, and what might work for one person might not be appropriate for another. So, how do you choose which treatment is right for a patient?   

Dr, Yacoub:

Excellent. So, and that’s actually the heart of what we define as the art of practicing medicine and being patient-centric and focused. And patients already have their own wishes and their needs. And everything should start with having a discussion with patients on what is their priority, and what are they trying to achieve.  

And we do have to explain to them the tools we have, the interventions that can help them. But we also need to make sure they’re compatible with what they actually want and their goals in life. And sometimes what we doctors want is not exactly what the patients want. So, we always have to remind ourselves that patients are the drivers of their care. And they have the absolute right to be informed and to make informed decisions based on the options we advise them about.  

So, that is always a centerpiece of healthcare. And then patients – basically, we defined four pillars of care. We want to control their symptoms, we want to prevent complications, we want to modify the disease so it doesn’t transform, and we want our therapies not to have toxicities, not to have side effects that are worse than the disease.  

So, we bring that up to the table. And we also look at the patient. What are their symptoms? What did the disease cause them to be complications?  

What is the risk that their cancer is actually going to progress quickly to hurt their lives? And how serious is the therapy we’re recommending? And we need to make sure that there is a good match between what we’re offering and what the disease is manifesting. So, for example, for patients who have a lot of symptoms, but they have low-risk cancer that they can live with for a long time, we focus on symptoms. We focus on treatments that improve their symptoms.  

While with patients who have more serious diseases that are eminently life-threatening, we focus on an expedited path to a more aggressive therapy and a bone marrow transplant.  

And then we also try to match those therapies with the other patient’s wishes and needs and so forth. So, all these factors are important. We have more tools to try to prognosticate. So, prognosticate is the medical word that we use as forecasting.  

We like to forecast the disease or the cancer. We try to predict the patient’s future. Fortunately, we actually have good tools to prognosticate now. We have models or calculators that factor in patients’ features, their symptoms, their age, their blood counts, their bone marrow findings, and their DNA mutations. And it gives us a score, a risk score that can correlate with their life expectancy or their outcomes.  

And we use those tools to guide us. So, there’s actually a tool we use to help patients reach that decision. It’s an objective tool to decide how serious is this disease and how seriously we should tackle it. It’s very applicable for patients with myelofibrosis, more sort of the other lower-risk cancers.  

Katherine:

What about comorbidities? How do they fit into the treatment plan?  

Dr. Yacoub:

Very important.  

So, again, it also goes back to finding the balance between how serious is the disease, how serious is the treatment, and how will the patient’s general health tolerate and factor in the choices patients make accordingly. So, myeloproliferative neoplasms do happen in a broad range of ages. And we have children, minors with MPNs, and we have elderly patients with MPNs. And it’s a continuous spectrum. And each individual patient will have their own health concerns and their own health comorbidities and their own wishes. And we always have to make sure that we match our therapies, the disease seriousness, and the patient’s wishes, which is also stemming from their own other health battles, too.  

We cannot turn a blind eye to the other health issues going on. That plays a major factor as we choose to discuss bone marrow transplantation with patients. Because that’s when the medical comorbidities are often the first barrier to go through.  

Katherine:

Are there specific biomarkers that may affect prognosis or treatment?  

Dr. Yacoub:

Yes. So, and we’re glad that actually myeloproliferative neoplasms are actually the model in medical oncology on how predictors can tell us a lot more about the patient’s future about the prognosis. So, early on in MPNs, we’ve developed models, like the International Prognostic Scoring Systems in many different iterations. And more recently, the Molecular Based International Prognostic Scores.  

They factor in patient’s age, they factor in blood numbers, they factor in DNA abnormalities, they also factor in DNA mutations, including the common driver mutations JAK2 and CALR and MPL, as well as more novel mutations that we call higher risk mutations.  

So, based on these models, we use these tools to predict how the cancer will behave, and how to approach it. This advancement has been an application for our MPN patients for a while, way ahead of all other fields of oncology. So, we’re proud that we can give our patients this tool before all other doctors were able to. Yeah.   

What Are Treatment Options for Myelofibrosis?

What Are Treatment Options for Myelofibrosis? from Patient Empowerment Network on Vimeo.

MPN specialist Dr. Abdulraheem Yacoub shares and overview of treatment options, including therapies in development, for patients living with myelofibrosis (MF).

Dr. Abdulraheem Yacoub is a hematologist oncologist at the University of Kansas Cancer Center. Dr. Yacoub is an active researcher and is an Associate Professor of Hematologic Malignancies and Cellular Therapeutics. Learn more about Dr. Yacoub, here.

 
 

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How Treatment Goals Impact MPN Treatment Decisions

How Treatment Goals Impact MPN Treatment Decisions

Advice for Choosing MPN Therapy: What’s Right for You?

Advice for Choosing MPN Therapy: What’s Right for You?

How Should You Participate in MPN Care and Treatment Decisions?

How Should You Participate in MPN Care and Treatment Decisions?


Transcript:

Katherine:

And since myelofibrosis is a progressive condition, I imagine it’s more difficult to manage. So, what else is available for patients with myelofibrosis?  

Dr. Yacoub:

Correct So, myelofibrosis is the higher end of this spectrum of cancers.  

It is a cancer that is associated with much higher symptom burden and impact on daily life. It is also associated with low blood counts, and some patients will require transfusions. It’s a major morbidity to our patients. And in addition, it’s a cancer that is associated with shortened life. So, patients with myelofibrosis will not live as long as their health would have allowed them. And some of them will live actually a much shorter life than they want or deserve.  

So, myelofibrosis treatment requires a lot more considerations. So, for patients who are in good health, who have a cancer that is more aggressive, that would be imminently impacting their longevity, we start a discussion about a curative role of allogeneic stem cell transplantation very early in their course.  

Because bone marrow transplantation can be curative, and those patients can live a long life after a successful transplant. So, this is a treatment modality that should be brought up very early for patients with higher risk myelofibrosis. There are approved JAK inhibitors, ruxolitinib (Jakafi) and fedratinib (Inrebic). And we know that ruxolitinib which has been approved for over 10 years can improve symptoms, can improve the spleen volume, can actually prolong lives for patients on it, and also makes the transplant more successful.  

So, we should be offering that to the appropriate patients also early in their diagnosis, in a strategy where, in addition to that, we get them to a transplant. Fedratinib is approved in that setting. And we are very optimistic that by the end of this calendar year, we will have two other JAK inhibitors approved.  

[Editor’s Note: As of February 28, 2022, pacritinib (Vonjo) has been approved for the treatment of myelofibrosis patients with severe thrombocytopenia.] 

So, we look forward to those two drugs. Momelotinib and pacritinib for patients with special disease features. And hopefully, by the end of this year, we will have a list of JAK inhibitors that we can choose from, which is great news for our patients.  

Katherine:

Oh, we’re still fighting. 

Dr. Yacoub:

Yes, absolutely.  

What Are Treatment Options for Polycythemia Vera?

What Are Treatment Options for Polycythemia Vera? from Patient Empowerment Network on Vimeo.

MPN specialist Dr. Abdulraheem Yacoub provides an overview of available treatment options for patients living with polycythemia vera (PV). 

Dr. Abdulraheem Yacoub is a hematologist oncologist at the University of Kansas Cancer Center. Dr. Yacoub is an active researcher and is an Associate Professor of Hematologic Malignancies and Cellular Therapeutics. Learn more about Dr. Yacoub, here.
 
 

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How Treatment Goals Impact MPN Treatment Decisions

How Treatment Goals Impact MPN Treatment Decisions

Advice for Choosing MPN Therapy: What’s Right for You?

Advice for Choosing MPN Therapy: What’s Right for You?

How Should You Participate in MPN Care and Treatment Decisions?

How Should You Participate in MPN Care and Treatment Decisions?


Transcript:

Katherine:

You mentioned using interferons for ET. That’s something that you would also use for polycythemia vera. Yes?   

Dr. Yacoub:

Absolutely. So, the same principles will apply to polycythemia vera. We would like to treat the higher-risk patients more aggressively. Hydroxyurea (Hydrea) and interferon are also the first-line therapies in these patients.   

The good news in 2022 is that we actually finally have an FDA-approved interferon for our patients. Finally, after 50 years of using interferon, now, we have an FDA approval. So, the new interferon, ropeginterferon alfa-2b is a medication that was studied prospectively in Europe, and it has been approved and in clinical use in Europe under the brand name Besremi.  

And this year, it was approved in the U.S. for patients with polycythemia vera, which is a great achievement for the medical field and a great tool to help our patients. We have used other brands off-label in the past, but it’s glad now to get this confirmation from the FDA that this is a standard of care for all patients.  

And then beyond that, ruxolitinib or Jakafi, is also approved as a second-line option in patients who have had hydroxyurea as their first line.  

So, these are the medicines we use for polycythemia vera. We also use therapeutic phlebotomy. And the goal in high-risk polycythemia vera, or actually in all patient polycythemia vera, is to reduce their hematocrit.  

And we want it under 45 percent every day of the year. And we use the tools that we just discussed phlebotomy and medicines to achieve that, in addition to aspirin. So, that’s how PV is more unique than ET. Yes. 

Thriving with an MPN: What You Should Know About Care and Treatment

Thriving with an MPN: What You Should Know About Care and Treatment from Patient Empowerment Network on Vimeo.

 MPN specialist and researcher, Dr. Abdulraheem Yacoub, reviews factors that help guide care decisions for MPNs – essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). Dr. Yaboub discusses the goals of treatment, shares tools for taking an active role in your care, and provides an update on promising new therapies for MPNs.

 
Dr. Abdulraheem Yacoub is a hematologist oncologist at the University of Kansas Cancer Center. Dr. Yacoub is an active researcher and is an Associate Professor of Hematologic Malignancies and Cellular Therapeutics. Learn more about Dr. Yacoub, here.
 
 

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The Latest in MPN Research: Updates from ASH 2021

The Latest in MPN Research from ASH 2021

Updates from ASH: How Biomarker Testing Has Changed MPN Care

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Expert Advice for Finding an MPN Clinical Trial

Expert Advice for Finding an MPN Clinical Trial


Transcript:

Katherine:                  

Hello, and welcome. I’m Katherine Banwell, your host for today. Today’s program is about how to live and thrive with an MPN. We’re going to discuss MPN treatment goals, and how you can play an active role in your care.

Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you.

All right, let’s meet our guest. Joining me today is Dr. Abdulraheem Yacoub. Welcome, Dr. Yacoub. Would you please introduce yourself?

Dr. Yacoub:               

Hello, Katherine. And thank you very much for inviting me to participate in this very important and near and dear topic to my heart and to everything I do every day.

I’m a hematologist-oncologist at the University of Kansas. I practice hematology 100 percent of my time, and I dedicate it to patients with MPNs. I’m an active researcher through clinical trials at my own institution, as well as part of many national and international collaborations. We all strive to provide the best care and the updates for our patients. I’m also a Director of our hematology clinics in cancers at the University of Kansas, and I’m an Associate Professor of Medicine at the University of Kansas.

Katherine:                  

Well, thank you so much for taking time out of your very busy schedule to join us today. We appreciate it.

Dr. Yacoub:               

Absolutely, my pleasure.

Katherine:                  

To give our patient audience some context before we get into the specifics of MPN treatment approaches, how would you define treatment goals?

Dr. Yacoub:               

Thank you, thank you. And I always like to highlight and emphasize that unlike many of the cancer syndromes that patients deal with, myeloproliferative neoplasms are unique.

These are chronic cancers. There’s no finish line. And this is a disease you live with. It affects every day of your life, every activity of your future life. You plan your life events accordingly. Pregnancies and marriages and trips and all of that. So, this is a chronic cancer. And as we plan therapy, we always factor that in. We would like the cancer to have the least or almost no impact on your daily life.

Whether it’s symptoms, whether it’s disability and dysfunction and inability to perform your daily functions, whether it’s actual physical symptoms that you’re having from the cancer, or whether it’s affecting complications that are hurting your health. So, we would like to focus on all of these, the medical aspect as well as the impact of the disease to everyday symptoms.

This is a unique feature of these cancers. And it doesn’t really exist much in other diseases.

Katherine:                  

That’s helpful to understand as we move through today’s program. And we’re going to cover the three classic MPNs, polycythemia vera, essential thrombocythemia, and myelofibrosis.

So, for the person who has one of these conditions, can you help us understand the treatment approaches for each? Let’s start with essential thrombocythemia or ET.

Dr. Yacoub:               

Excellent. So, I’m going to start with some general concepts. So, as we approach our patients, we would like to get a good assessment of the disease burden to their lives. These can be symptoms. So, we actually have very good objective tools to measure symptoms, such as the MPN-SAF. It’s an objective tool to calculate the symptoms. So, we would like to get an objective baseline of symptoms.

Because we do want to address the symptoms, regardless of the MPN subtype. We do want to master actually the symptoms because that is what patients feel every day and we want to affect that early in the treatment. We also would like to get a good assessment of the disease complications. Have the patient suffered a clot or a hemorrhage or symptoms because of an enlarged spleen? Or were they unable to perform certain activities? Are they able to eat? Are they losing weight?

So, we would like to see how is the cancer also causing them immediate morbidity, and we also would like to tackle the future. So, cancers tend to get worse with time. They tend to transform into a higher risk cancer. So, as we approach any of the MPN patients, we also talk about the future risk of the cancer turning into a more aggressive form of cancer.

So, we would like if we can, for every patient to focus on these three pillars of their care: their immediate quality of life and symptoms, their immediate complications, and their future disease progression.

And we would like to factor in that our treatments does not add more side effects to their lives. So, that’s the fourth pillar of how we take care of patients. So, these are the basic concepts that will apply today for all patients with all three diseases.

Some patients will have more emphasis on one or the other. But this is something in our mind as doctors who treat MPN patients, we try to balance all these three pillars for every patient. So, let’s talk about essential thrombocythemia. This is among the other MPNs, the cancer with the lowest risk. Patients with essential thrombocythemia can have clots and can have bleedings. And they also often have symptoms because of their cancer.

But they also enjoy a long life expectancy that is almost indifferent from patients who don’t have cancer provided they get good care. So, our emphasis is on focusing that their life quality is not touched by their cancer, and focusing on treating patients with symptoms, to ameliorate the symptoms and allowing them to have a decent and good quality of life. At the same time, we would like to reduce the risk of clotting and bleeding.

And we have tools and medicines that are very effective at doing that in select patients who we define as high risk. And now there is a more clear definition of that. So, high-risk patients are patients who are over age 60 and have a JAK2 mutation, or patients who have already had a clot.

That is not the majority of ET patients actually. The majority are not high risk. And those patients might not require therapy to reduce their platelet count.

But for high-risk patients, we have tools to help them. So, hydroxyurea (Hydrea) is the most commonly used medicine in this setting.

The goal of hydroxyurea is to reduce the platelet count. And we’d like to keep it under 400, sometimes under 600 under different circumstances. And that will reduce the risk of clotting and bleeding for our patients. The other option, which I also feel passionate about is interferon.

Interferons are drugs that we’ve used for decades. They’re very effective. They’re safe in the right hands.

And they do have advantages over hydroxyurea in terms of long-term safety. These are medications we can give to young patients, we can give to pregnant patients, we can give for long term without concerns of toxicity, and also they have a higher ceiling. Patients with interferon can achieve a disease control that we cannot achieve with hydroxyurea.

And this will be beneficial long term treating those patients. So, these – Yeah, and then aspirin therapy is always something we would like to include in this regimen.

Katherine:                  

I was going to ask you about that. So, aspirin is still being used as a treatment?

Dr. Yacoub:               

Absolutely. So, the standard of care is to use aspirin. Usually, one baby aspirin once a day, preferably in the morning is what we recommend. And that’s probably all the aspirin they need. We do not want them to take more than that either.

Katherine:                  

And you mentioned using interferons for ET. That’s something that you would also use for polycythemia vera. Yes?

Dr. Yacoub:               

Absolutely. So, the same principles will apply to polycythemia vera. We would like to treat the higher-risk patients more aggressively. Hydroxyurea and interferon are also the first-line therapies in these patients.

The good news in 2022 is that we actually finally have an FDA-approved interferon for our patients. Finally, after 50 years of using interferon, now, we have an FDA approval. So, the new interferon, ropeginterferon alfa-2b is a medication that was studied prospectively in Europe, and it has been approved and in clinical use in Europe under the brand name Besremi.

And this year, it was approved in the US for patients with polycythemia vera, which is a great achievement for the medical field and a great tool to help our patients. We have used other brands off-label in the past, but it’s glad now to get this confirmation from the FDA that this is a standard of care for all patients.

And then beyond that, ruxolitinib or Jakafi, is also approved as a second-line option in patients who have had hydroxyurea as their first line.

So, these are the medicines we use for polycythemia vera. We also use therapeutic phlebotomy. And the goal in high-risk polycythemia vera, or actually in all patient polycythemia vera, is to reduce their hematocrit.

And we want it under 45 percent every day of the year. And we use the tools that we just discussed phlebotomy and medicines to achieve that, in addition to aspirin. So, that’s how PV is more unique than ET. Yes.

Katherine:                  

And since myelofibrosis is a progressive condition, I imagine it’s more difficult to manage. So, what else is available for patients with myelofibrosis?

Dr. Yacoub:               

Correct So, myelofibrosis is the higher end of this spectrum of cancers.

It is a cancer that is associated with much higher symptom burden and impact on daily life. It is also associated with low blood counts, and some patients will require transfusions. It’s a major morbidity to our patients. And in addition, it’s a cancer that is associated with shortened life. So, patients with myelofibrosis will not live as long as their health would have allowed them. And some of them will live actually a much shorter life than they want or deserve.

So, myelofibrosis treatment requires a lot more considerations. So, for patients who are in good health, who have a cancer that is more aggressive, that would be imminently impacting their longevity, we start a discussion about a curative role of allogeneic stem cell transplantation very early in their course.

Because bone marrow transplantation can be curative, and those patients can live a long life after a successful transplant. So, this is a treatment modality that should be brought up very early for patients with higher risk myelofibrosis. There are approved JAK inhibitors, ruxolitinib and fedratinib (Inrebic). And we know that Ruxolitinib which has been approved for over 10 years can improve symptoms, can improve the spleen volume, can actually prolong lives for patients on it, and also makes the transplant more successful.

So, we should be offering that to the appropriate patients also early in their diagnosis, in a strategy where, in addition to that, we get them to a transplant. Fedratinib is approved in that setting. And we are very optimistic that by the end of this calendar year, we will have two other JAK inhibitors approved.

So, we look forward to those two drugs. Momelotinib and pacritinib for patients with special disease features.

[Editor’s Note: As of February 28, 2022, pacritinib (Vonjo) has been approved for the treatment of myelofibrosis patients with severe thrombocytopenia.]

And hopefully, by the end of this year, we will have a list of JAK inhibitors that we can choose from, which is great news for our patients.

Katherine:                  

Oh, we’re still fighting.

Dr. Yacoub:               

Yes, absolutely.

Katherine:                  

As with most conditions, all patients are different, of course, and what might work for one person might not be appropriate for another. So, how do you choose which treatment is right for a patient?

Dr, Yacoub:               

Excellent. So, and that’s actually the heart of what we define as the art of practicing medicine and being patient-centric and focused. And patients already have their own wishes and their needs. And everything should start with having a discussion with patients on what is their priority, and what are they trying to achieve.

And we do have to explain to them the tools we have, the interventions that can help them. But we also need to make sure they’re compatible with what they actually want and their goals in life. And sometimes what we doctors want is not exactly what the patients want. So, we always have to remind ourselves that patients are the drivers of their care. And they have the absolute right to be informed and to make informed decisions based on the options we advise them about.

So, that is always a centerpiece of healthcare. And then patients – Basically, we defined four pillars of care. We want to control their symptoms, we want to prevent complications, we want to modify the disease so it doesn’t transform, and we want our therapies not to have toxicities, not to have side effects that are worse than the disease. So, we bring that up to the table. And we also look at the patient. What is their symptoms? What did the disease cause them to be complications?

What is the risk that their cancer is actually going to progress quickly to hurt their lives? And how serious is the therapy we’re recommending? And we need to make sure that there is a good match between what we’re offering and what the disease is manifesting. So, for example, for patients who have a lot of symptoms, but they have low-risk cancer that they can live with for a long time, we focus on symptoms. We focus on treatments that improve their symptoms.

While with patients who have more serious diseases that are eminently life-threatening, we focus on an expedited path to a more aggressive therapy and a bone marrow transplant. And then we also try to match those therapies with the other patient’s wishes and needs and so forth. So, all these factors are important. We have more tools to try to prognosticate. So, prognosticate is the medical word that we use as forecasting.

We like to forecast the disease or the cancer. We try to predict the patient’s future. Fortunately, we actually have good tools to prognosticate now. We have models or calculators that factor in patients’ features, their symptoms, their age, their blood counts, their bone marrow findings, and their DNA mutations. And it gives us a score a risk score that can correlate with their life expectancy or their outcomes.

And we use those tools to guide us. So, there’s actually a tool we use to help patients reach that decision. It’s an objective tool to decide how serious is this disease and how seriously we should tackle it. It’s very applicable for patients with myelofibrosis, more sort of the other lower-risk cancers.

Katherine:                  

What about comorbidities? How do they fit into the treatment plan?

Dr. Yacoub:               

Very important.

So, again, it also goes back to finding the balance between how serious is the disease, how serious is the treatment, and how will the patient’s general health tolerate and factor in the choices patients make accordingly. So, myeloproliferative neoplasms do happen in a broad range of ages. And we have children, minors with MPNs, and we have elderly patients with MPNs. And it’s a continuous spectrum. And each individual patient will have their own health concerns and their own health comorbidities and their own wishes. And we always have to make sure that we match our therapies, the disease seriousness, and the patient’s wishes, which is also stemming from their own other health battles, too.

We cannot turn a blind eye to the other health issues going on. That plays a major factor as we choose to discuss bone marrow transplantation with patients. Because that’s when the medical comorbidities are often the first barrier to go through.

Katherine:                  

Are there specific biomarkers that may affect prognosis or treatment?

Dr. Yacoub:               

Yes. So, and we’re glad that actually myeloproliferative neoplasms are actually the model in medical oncology on how predictors can tell us a lot more about the patient’s future about the prognosis. So, early on in MPNs, we’ve developed models, like the International Prognostic Scoring Systems in many different iterations. And more recently, the Molecular Based International Prognostic Scores.

They factor in patient’s age, they factor in blood numbers, they factor in DNA abnormalities, they also factor in DNA mutations, including the common driver mutations JAK2 and CALR and MPL, as well as more novel mutations that we call higher risk mutations.

So, based on these models, we use these tools to predict how the cancer will behave, and how to approach it. This advancement has been an application for our MPN patients for a while, way ahead of all other fields of oncology. So, we’re proud that we can give our patients this tool before all other doctors were able to. Yeah.

Katherine:                  

That’s excellent. Dr. Yacoub, what is the role of the patient in their care? When does shared decision-making come into play?

Dr. Yacoub:               

Absolutely.

Patients are the drivers and the centerpiece of their health care. And patient self-advocacy is the most important tool. So, many of our patients are young and they will live with their cancers a lot longer than many cancer doctors will practice oncology. And they will have many doctors. Statistically, each MPN patient will have multiple doctors throughout their career. And they will hear different derivatives. And the science will change. And they will be given different counseling over the time. And their disease will change.

And they will have different needs as they go further. So, patients being involved in their wellbeing and their cancer care is important from the first day. And I always tell patients, “You need to start building your village from day one.” It is not just the patient, it’s your caregivers, it’s who else can help you.

Who else can advise you? You might want to also invest in a friend or a spouse or a child, to come to you and listen to some of those discussions so that they can advise you later on, “Why are you making different decisions?” So, we encourage patients to be very involved early on, to build their own village, and to seek care. We routinely ask for second opinions. We want patients to always hear the story and hear the same story from another doctor so that they hear the range of how we word the truth and how we word the facts.

And this way, they can have a better perspective. So, this is now a standard. Almost all patients should have two doctors, at least, the treating doctor and one doctor who’s an MPN specialist, who would give them another twist or another perspective to their health.

So, and that is always important. And then there are very good references and online resources for patients to tackle in, such as this seminar and other good places where patients can seek more information. They also can go to a clinical trial to find out what are the ongoing clinical trials and advancements.

There are structured patient symposiums nationally and regionally. So, and we strongly recommend that patients seek more opinions and more help and more resources and be very engaged with this disease, especially that it is a chronic cancer, and it’s not going to –

Katherine:                  

It’s not going away.

Dr. Yacoub:               

It’s just a new lifestyle. And they need to be as engaged with it as they can.

Katherine:                  

Absolutely. We have a couple of questions from the audience. This one is from Sarah. She writes, “I’ve been living with essential thrombocythemia for three years, and have been relatively stable. Of course, I’m worried about progression to PV or MF. What is my chance of progression, and what are the signs of progression?”

Dr. Yacoub:               

That’s a very good question. And unfortunately, we’re very good at describing those numbers. Unfortunately, our tools at interfering are not as good. So, in general, patients with ET, statistically speaking, have a life expectancy that is not different from their age match peers. And Sarah’s story will be not too indifferent from her sisters and her mother, in terms of what’s going to happen to her long care and her health, provided she gets good medical care. The exception to that is that there is a transformation risk. For ET we caught around a 4 percent every 10 years in which ET will actually change into a different cancer, a higher risk cancer.

Could be MF, could be MDS, could be acute leukemia. And that will be a much more serious diagnosis. So, it’s about 4 percent in 10 years. We do have a – or we extrapolate some of the data from other cancers. So, certain mutations are more favorable, certain mutations are more risky. And we try to forecast that but worried it’s really hard to predict that since it’s such a long journey with disease. The first symptoms or the findings, when patients start suspecting that their disease has changed, is that the pattern of symptoms that they have are different.

They often become worse. So, they have more constitutional symptoms, more tiredness, more fevers, more night sweats, losing weight, not being able to eat a full meal, abdominal distension, the spleen gets bigger.

So, these are some of the feelings that patients can experience that lead to this. Other objective things is when the blood tests change in a less favorable way. So, for patients with ET who always run at 800,000 platelet count, if they’re suddenly 200, and that’s in the normal range, but that’s actually not good news, because the cancer changed. And this change is not favorable. So, as the doctors run routine labs, if they see the sudden change in labs, that’s also abnormal.

If the doctor can feel that the spleen gets bigger every time, that’s also concerning. If the patients suddenly have anemia or very high white cell count or immature white cells in the blood, that’s also a concern.

So, that’s why it’s great or important to establish a baseline symptom burden.                                   

A baseline spleen, a baseline bone marrow biopsy with mutation analysis, so that patients have a clear reference point to where they started, and if things change, they can always go back to that point and compare.

Katherine:                  

Right. We have another question. This one from Victor. He says, “I was diagnosed with PV in 2018. And I’ve been treated with hydroxyurea. Recently, I’ve been very fatigued. I want to exercise, but I don’t have the energy to do much. Do you have any advice for boosting my energy?”

Dr. Yacoub:               

That is a very good question and very common question. So, the causes for fatigue in adults, in general, so many. And adding PV to that adds a few other reasons why one would be more fatigued. So, assuming that Victor follows with his doctor, and his primary care doctor has systematically went through all the possible causes for fatigue, and those were addressed.

Now that PV specific causes, A). Hydroxyurea can cause fatigue. So, maybe it’s the hydroxyurea dose. And that’s a side effect. And maybe that’s not the best medicine for him. B). Polycythemia vera can cause fatigue. Maybe we’re not controlling it enough. Maybe we need to dial up the dose of the medicine or dial down the dose of the medicine accordingly. And then there’s also the iron deficiency which we induce with PV and phlebotomy.

And whether we actually have taken Victor to become very low on iron, and that can cause fatigue. So, we have to evaluate the treatments, the disease, and the side effects of the interventions we’ve done. And those are the polycythemia vera specific factors that can add to the fatigue.

Katherine:                  

Here’s another question from the audience. This is from Sandy. She writes, are MPNs hereditary? Should my children or siblings be aware of their risk?

Dr. Yacoub:               

All right. Well, the answer to that question changed many times over the last 10 years. So, the answer changed from absolutely not, to very possibly maybe over the years. So, although we don’t think of cancers as inherited, it’s not passed from one parent to their children. But MPNs tend to run in families. And for 11 percent of patients with MPN, and that number has also increased over the years, have actually a first-degree family member with MPN. That is a big coincidence, it’s almost too high to be a coincidence. So, we are realizing that there is genetic makeup or clustering that can cause MPNs to happen more often in certain families.

So, how does this apply to patients? So, if a patient has MPN, that does not mean that their children or siblings will get MPN, it just means they’re more likely than the other people to have MPN, just because they all share the same genetic makeup. And they should be made aware. And they should maintain good health care and maintain the relationship with a primary and have routine labs and all that. But not necessarily that they will get cancer. This still is a very rare disease, and 11 percent of a rare disease still is a small number.

Katherine:                  

Thank you for answering those patient questions. I appreciate it.

Dr. Yacoub:               

My Pleasure.

Katherine:                  

And to our patients, please continue to send in your questions to question@powerfulpatients.org and we’ll work to get them on future programs.

So, Dr. Yacoub, as we close out our program and our conversation, I wanted to get your take on the future of MPN research and treatment. Are there new developments that you’re excited about and that make you hopeful?

Dr. Yacoub:               

Absolutely. So, again, I would like to take the last few minutes to advocate for the future. And the future can only come when doctors and patients and advocates work together to advance the science. We have few tools to treat patients and to help patients. We have a lot of unanswered questions. And the only way to answer them is by designing quality clinical trials, enrolling patients on trials, taking the risk, and trying to find new answers and new therapeutics. So, I always would like to advocate for patients to seek clinical trials whether with their doctor or whether they have to travel for it, and for doctors to consider that for their patients. That’s the only way to advance science.

There are very important national and international studies going on right now. One of the – And first, I would like to emphasize is that we have had ruxolitinib as the only therapy, or the first-line therapy for myelofibrosis for a decade now. Not everybody responds to it, not everybody responds to it for a long time. So, now we’re designing combination trials. So, there’s a few studies that are trying to redefine, “Is ruxolitinib alone enough, or should we have a combination first-line therapy?” So, these are some of the more important questions being asked right now.

And this is definitely one of the bigger moves in the field, is trying to redefine what is the first-line therapy for myelofibrosis. For polycythemia vera, we’re also exploring therapeutics that would reduce phlebotomy with things you can add to your medical care to reduce phlebotomy.

So, that’s also going on. And it’s definitely a big leap forward for many of our patients. For ET, when we don’t have any actual drugs approved other than hydroxyurea and anagrelide (Agrylin), we actually have trials with interferon going on.

So, I would like to advocate for that. So, interferon succeeded and now approved for PV, but not yet for ET. We’re working on that. So, again, in every disease, we’re trying to design clinical trials to redefine what is the best treatment today.

We’re also doing studies to understand the cancer. So, studies where patients donate their samples for research. These are very helpful, very important. And contributing to that always advances the science, and it’s low effort to the patients. So, if there’s a clinical trial that is offered to patients, I would strongly urge everybody to consider that favorably and contribute to science.

That’s the only way we can help future patients and ourselves immediately, at moving the field forward.

Katherine:                  

Seems like there’s a lot of progress in the field.

Dr. Yacoub:               

A lot of progress. I look forward to future events. I’m going to have a lot more tools to discuss. Hopefully, by this time next year, we’re going to have four JAK inhibitors, injectables for PV, interferon for ET, and a lot more things to go over.

Katherine:                  

That’s wonderful. Dr. Yacoub, thank you so much for taking the time to join us today.

Dr. Yacoub:               

You’re welcome. And it’s my pleasure. I feel passionate about this. And I’m happy to help.

Katherine:                  

Thank you. And thank you to all of our partners. To learn more about MPNs and to access tools to help you become a productive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us today.

Updates from ASH: How Biomarker Testing Has Changed MPN Care

Updates from ASH: How Biomarker Testing Has Changed MPN Care from Patient Empowerment Network on Vimeo.

MPN specialist, Dr. Andrew Kuykendall, discusses how the identification of specific biomarkers in myeloproliferative neoplasms (MPNs), such as the JAK2 mutation, have moved research forward. Dr. Kuykendall shares promising findings that were released at the 2021 American Society of Hematology (ASH) annual meeting and how this may impact MPN care in the future.

Dr. Andrew Kuykendall is an Assistant Member at Moffitt Cancer Center in the Department of Malignant Hematology. Dr. Kuykendall’s clinical and research efforts focus on myeloproliferative neoplasms (MPNs), MDS/MPN overlap syndromes and systemic mastocytosis (SM). Learn more about Dr. Kuykendall, here.

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Transcript

Katherine:

How has molecular or biomarker testing changed the field of MPN care and treatment?

Dr. Kuykendall:

Well, I think, first and foremost just understanding – going back to 2005 and knowing that we have JAK2 mutations. I think that gave really a lot of clarity to the diagnosis and really understanding the biology of how the disease acted through the JAK-STAT pathway. And certainly, that led to the understanding of MPL mutations and then calreticulin mutations.

We’re still figuring out exactly how calreticulin mutations work. There was a great abstract, a preclinical abstract, this year talking about the impact of interferon on calreticulin mutations and how that may differ from what we see in the impact of interferon on diseases that are driven by JAK2 mutations.

Clinically, we see a little bit of difference in how those diseases respond and we may understand a little bit better about why that happens. Additionally, that’s kind of gone down to looking at these big next generation sequencing panels where we identify high-risk mutations and that can certainly change our understanding of the prognosis of these diseases.

We’re starting to get, at least in the AML world, we’re getting targeted agents that can potentially target some of these mutations such as IDH1 and IDH2 mutations that have specific inhibitors.

Those are mutations that occur in myeloproliferative neoplasm patients and convey a worse prognosis, so there are ongoing trials looking to see if we can use those IDH inhibitors in myeloproliferative neoplasms either in the chronic phase or maybe in the more accelerated advanced phase.

You know the big thing, this meeting, was actually looking at polycythemia vera patients and what’s the relevance of the JAK2 mutant allele burden. I think this is something we’ve talked about a lot as far as how significant this is. We know in chronic phase myeloproliferative neoplasms that that JAK2 mutation tends to be associated with more thrombotic complications.

There are more blood clots in the veins and the arteries. There were a couple great abstracts that looked at the really the implications of the JAK2 mutation and the fact that it is associated with more thrombosis, but maybe more venous thrombosis. That might be a big risk factor for venous thrombosis and it may be that cardiovascular risk factors, such as diabetes, hyperlipidemia that’s really what’s driving the arteriole thrombosis. It also looked at the variant allele fraction, the number of cells that have that JAK2 mutation.

One abstract showed that if you have over a 50 percent allele fraction, if more than 50 percent of the alleles have the mutation – a higher burden of that mutation that’s associated with an increased thrombotic risk even in low-risk polycythemia vera patients. Whether or not that’s enough evidence to really change the paradigm of how we treat low-risk patients is to be determined, but I think very interesting and provocative work.