Tag Archive for: blood clot

What Factors Guide Treatment Choices for ET, PV & MF?

What Factors Guide Treatment Choices for ET, PV & MF? from Patient Empowerment Network on Vimeo.

When making a myeloproliferative neoplasm (MPN) treatment decision, several factors come into play. Dr. Brady Stein explains what criteria he considers to determine the optimal approach for a patient’s unique situation and specific MPN.

Dr. Brady Stein is a hematologist focusing on myeloproliferative neoplasms (MPNs) at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more about Dr. Stein, here.


Related Resources

Monitoring MPNs: When is it Time to Switch Therapies?

An Expert Shares Key Steps to Take Following an MPN Diagnosis

MPN Treatment: Why Testing for Mutations Matters


Transcript:

Katherine:              

Dr. Stein, I understand that therapy is different for each of the MPNs. What do you take into consideration to help guide the treatment choice?

Dr. Stein:                   

So, that’s a good question. It’s going to require maybe a little bit of a longer answer. It’s fairly nuanced. The treatment of ET and PV – right now, the goals are – the treatment is largely based on a patient’s vascular risk. That’s largely what influences the choice of therapy. And so if a patient has a perceived high risk for vascular complication in ET or PV, that’s when we’re going to be a little bit more aggressive – so, more aggressive than watchful waiting, more aggressive than using aspirin alone, more aggressive than using phlebotomy and aspirin alone in polycythemia vera.

So, if the patient has a higher vascular risk, in general, we’re going to need to do something more than what we consider to be the standard, and that’s where we enter into the question of cytoreductive therapy – therapies designed to lower blood counts apart from phlebotomy.

Maybe that’s going to change. I hope it will change. Right now, the therapy for ET and PV is generally reactive. We either predict high risk and react, or if a patient is lower risk, if something changes – God forbid there’s a blood clotting event – then we may react to it.

So, ET and PV treatment are generally more reactive. In myelofibrosis, certainly, there are patients who can have lower risk and minimal systems, and there are some patients who can be observed with watchful waiting for sure, but more patients are symptomatic, more patients are going to need therapy in myelofibrosis, and there’s sort of two big categories of therapy.

One is the risk-adapted, deciding if the patient is eligible and should consider stem cell transplant versus thinking only about medical therapy in a patient that may be transplant-ineligible.

And, the medical therapy is based on the worst symptoms for the patient. Is the symptom that’s the worst the spleen enlargement? Is it excessive fatigue? Is it weight loss, or inflammation, or fevers? If it’s that category of symptoms, we have a set of therapies. If it’s really the anemia that is the most problematic issue, then we follow a paradigm to treat anemia.

Katherine:                  

What about considerations like the patient’s health, age, genetic markers, things like that?

Dr. Stein:                   

So, of course. The comorbid illnesses can influence therapy choices, so if a patient is older and has other medical conditions, they’re not going to be treated as aggressively.

So, in myelofibrosis, if a patient is older, with other medical illnesses, then it may be inappropriate to consider something like stem cell transplant, for sure. So, age and health comorbidities are highly influential. In terms of genetic features, if you’re asking about things like the type of mutation that a patient has, right now, we’re – in terms of vascular risk, for ET, the type of mutation matters for blood clotting risk, so if patients have different mutations, it could be treated differently. In other subtypes, like PV or myelofibrosis, in general, there’s – the mutation can be prognostic, but it may not be – it may not lead to a precise and distinct therapy just yet.

How Do Test Results Inform MPN Prognosis & Treatment?

How Do Test Results Inform MPN Prognosis & Treatment? from Patient Empowerment Network on Vimeo.

Dr. Brady Stein explains the diagnostic tests and genetic mutations that are assessed to determine prognosis and what MPN treatment may work best.

Dr. Brady Stein is a hematologist focusing on myeloproliferative neoplasms (MPNs) at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. 


Related Resources

Which MPN Treatment is Right for You? Factors to Consider

Resource Guide: Choosing an MPN Treatment: What Option is Best for You?

MPN Treatment: Why Testing for Mutations Matters


Transcript:

Katherine:                  

Once a patient is diagnosed with MPN, what sort of testing should take place?

Dr. Stein:                   

So, the test that’s going to lead to suspicion is going to be a blood count, and that’s probably going to be done in the primary care doctor’s office, so that’s going to be the first suspicious test, and in general, there’s going to be some abnormality. Myeloproliferative diseases are characterized in general by an overproduction of blood cells, so it’s going to be a higher white count, it’s going to be a high hemoglobin or hematocrit, or a high platelet count, or a combination of the three that’s generally going to lead to suspicion.

Some patients may have pretty unremarkable blood counts and may present with a blood clot in an unusual location that could ultimately lead to the hematology referral. Some patients might have pretty unremarkable blood counts, but they might have palpation of their spleen, enlargement of their spleen in a physical examination. So, they’re generally the ways that patients are getting to the hematologist.

Katherine:                  

And, what about bone marrow biopsy?

Dr. Stein:                   

So, a bone marrow biopsy is a diagnostic test, and it’s generally recommended for all patients who have a myeloproliferative neoplasm either confirmed or suspected.

It’s advised in WHO criteria – World Health Organization criteria. PV can be made without a bone marrow biopsy – a diagnosis of PV – because it’s the most unique of the MPN subtypes. It’s the one that presents with a high hemoglobin.

So, that diagnosis can be straightforward at times for a hematologist when the setting is right, when there’s a high hemoglobin – or, high enough hemoglobin, I should say, a JAK2 mutation, which all patients with PV have that, or a subnormal erythropoietin level.

Oftentimes, we can make that diagnosis without a bone marrow, and the bone marrow becomes more prognostic. ET, a bone marrow is necessary for diagnosis, and myelofibrosis, you can’t make a diagnosis without it.

Katherine:                  

What do the results of these tests tell us about prognosis and treatment choices?

Dr. Stein:                   

That’s a good question. The bone marrow can be diagnostic in the setting of ET and myelofibrosis. In the setting of polycythemia vera, it can be more prognostic. In general, when a bone marrow is done, 1). To confirm diagnosis, 2). To assess prognosis, what we’re looking for as prognostic features are generally the degree of fibrosis or scarring.

So, each of the MPNs can have that. Of course, MF is characterized by the most pronounced scarring. It can happen to a more subtle degree in ET and PV. That’s going to be prognostic in the setting of ET or PV. The pathologist will alert us about immature cells called blasts.

We basically never see them at diagnosis in patients with ET or PV. We can see them rise in patients with myelofibrosis at diagnosis or through the course of follow-up. So, that’s prognostic.

All bone marrows generally have a chromosome analysis that’s called cytogenetics, and so, if there’s an abnormality, that can help place the patient’s prognosis into different risk categories.

And then, nowadays, more so in myelofibrosis than any of the others, there are extended panels done. These are called NGS, or next-generation sequencing, kind of looking at mutations in a greater degree of detail.

So, not just what we call main mutations – JAK2, calreticulin, or MPL. These are looking at additional mutations that basically hold prognostic significance.

These are pretty well defined, and I think more important in MF compared to the other subtypes.

Katherine:                  

Would you explain the driver mutations in MPNs? What are they, and how they – or, what they mean for patients?

Dr. Stein:                   

So, there’s three of what we call driver mutations, and the most common is JAK2V617F, the next most common is calreticulin, and the least common or most rare is a mutation of MPL, the thrombopoietin receptor. So, the driver gene mutations are the three that we assess to help with diagnosis, and the prevalence varies. In ET, about 60 percent have JAK2, 25 percent have calreticulin, 5 to 10 percent have MPL.

In PV, 99 percent have some type of JAK2 mutation, and in MF, the situation is a lot like ET – 60 percent JAK2, 25 percent calreticulin, about 5 to 10 percent MPL. So, the driver mutations – we think of those as the genetic abnormalities that really drive the disease. They’re the main ones we can test for in a diagnostic setting.

I refer to them as the – to a patient, what I’m describing is you have a car, and the driver mutation is the one that’s sort of driving the car, and it’s doing it somewhat recklessly. It’s in the front seat, driving. And, along the way, the driver can pick up hitchhikers, which we should never do. I refer to those other mutations that are found by NGS as hitchhiker mutations that sit in the back seat, cause trouble, and really shouldn’t be there. They’re not the driver, they’re not fully responsible for the disease, but they can make it a bit worse.

Tools to Help You Learn More About MPN Clinical Trials

Tools to Help You Learn More About MPN Clinical Trials from Patient Empowerment Network on Vimeo.

Research is quickly evolving for essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), all due to clinical trials. Dr. Laura Michaelis reviews tools for learning about clinical trials and how you can get involved. 

Dr. Laura Michaelis is hematologist specializing in myeloproliferative neoplasms (MPNs) at Froedtert & the Medical College of Wisconsin, where she also serves as Associate Professor of Medicine. Learn more about Dr. Michaelis here.


Related Resources

 

Promising ET, PV, & Myelofibrosis Therapies

 

Choosing an MPN Treatment: What Option is Best for You?

 

Could an MPN Clinical Trial Be Right for You?


Transcript:

Dr. Michaelis:                       

So, there’s lots and lots of research going on in the field of myeloproliferative neoplasms. One of the best ways to stay informed about this is to check on something called clinicaltrials.gov, which is a national website that warehouses clinical trials in the disease that you might have.

So, if you look up essential thrombocythemia or you look up myelofibrosis, it will show you the clinical trials that are going on in your region, in your state, or in the country. So, that’s a nice way to begin to look and see what’s available.

The other way, of course, is to talk to your doctor. And each institution has a list of clinical trials that they have open, based on what a person’s diagnosis is, what their age is, what other, for example, health issues that they might have. And so, again, when you’re talking to your doctor, say – Is there something I should be thinking about, in terms of clinical trials?

There are clinical trials going on in all facets of the disease – not just in treatment, which is what you often think about. Treatment for symptoms or treatment for ways to control the disease. There are new medicines coming down the road, in terms of what to do when somebody is no longer responding to treatment. Or how can we combine treatments together? Those are important trials, and those are things that people should talk with about their physician.

But there’s also clinical trials on symptom management, and those can sometimes be a trial that you would do online yoga or dietary trials. And there’s trials on familial syndromes, meaning – Yeah, I have polycythemia vera, and my aunt had myelofibrosis, and her daughter has ET. Well, that is a family that should be investigated. And sometimes we find that – even nationally, we find that we’re networking with one another and collecting patients who have family histories so we can learn more about that.

So, there’s a variety of different types of clinical trials. Those are things to talk to your doctor about. And on your own, you can search them out on clinicaltrials.gov or through patient advocacy organizations.

MPN Symptom or Treatment Side Effect? Know the Difference

MPN Symptom or Treatment Side Effect? Know the Difference from Patient Empowerment Network on Vimeo.

How do you distinguish MPN symptoms from side effects? Dr. Laura Michaelis explains the difference, and why it’s important to share any changes with your doctor.

Dr. Laura Michaelis is hematologist specializing in myeloproliferative neoplasms (MPNs) at Froedtert & the Medical College of Wisconsin, where she also serves as Associate Professor of Medicine. Learn more about Dr. Michaelis here.


Related Resources

 

What You Should Know About Progression in MPNs

 

Choosing an MPN Treatment: What Option is Best for You?

 

An Expert Summary of Current MPN Treatment Options


Transcript:

Dr. Michaelis:             

So, symptoms and side effects are sort of different things. Symptoms are the characteristics of the disease process. And these are things that often can vary in intensity. They maybe accumulate over time. But those are things like, for example, uncontrolled itching, fatigue, night sweats, fevers at night, unintentional weight loss, discomfort in the abdomen, or feeling full shortly after eating. Those are symptoms that often bring patients to the doctor’s attention in the beginning. And those are symptoms that can tell us that the treatments that we’re using aren’t working very well.

Now, side effects is the term that we use for problems that evolve when somebody starts a treatment for a condition. So, for example, if somebody starts the treatment of ruxolitinib for myelofibrosis, it is known that one of the side effects of this treatment is a small but significant lowering in the red blood cell [count].

That is a side effect of the ruxolitinib and should be anticipated. So, before you start the ruxolitinib, your doctor should sit down with you and talk about some of the side effects. And that might be one that gets mentioned.

In addition, we know that there is uncommonly – but uncommonly, people can have, for example, shingles reactivation once they’re taking treatment for myelofibrosis. And that might be something for which you take a prophylactic antiviral treatment.

Hydroxyurea has side effects. Interferon has side effects. And those are things that you should think about before you start them. They shouldn’t be reasons not to start the treatment because most people who take medicines don’t have the side effects. But it is something to keep in mind. And when then occur, report them to your doctor.

So, rarely, there’s conditions that occur, and you’re not sure. Is this a side effect to the treatment? Or does this mean the disease is progressing in some way? That’s one of the reasons it’s important to report all of these conditions to your physician because they need to know.

One of the things that can be helpful is there’s a common tool called the MPN SAF, which is a symptom assessment form.

If, periodically, you and your doctor fill that out during a clinic visit, you can sort of understand are those symptoms that I had with my disease responding to the treatment? Can we really measure that things have gotten better since I started treatment X or treatment Y?

And in addition, when you sit down with your doctor at your regular checkups, it’s not just about going through your blood counts and doing a physical exam. It’s also about telling them what you’ve noticed in the last two to three months since you saw your doctor with regard to the treatments that you’re taking.

Choosing an MPN Treatment: What Option Is Best for You?

Choosing an MPN Treatment: What Option Is Best for You? from Patient Empowerment Network on Vimeo.

When choosing an MPN treatment, what’s right for you? Dr. Brady Stein from Lurie Cancer Center reviews key decision-making factors, current treatments for ET, PV and MF, and shares advice on advocating for yourself.

Dr. Brady Stein is a hematologist focusing on myeloproliferative neoplasms (MPNs) at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more about Dr. Stein, here.

Download Program Resource Guide


Related Resources

 

What You Should Know About Progression in MPNs?

 

Monitoring MPNs: When is it Time to Switch Therapies?

 

An Expert Shares Key Steps to Take Following an MPN Diagnosis


Transcript:

Katherine:                   

Hello, and welcome to the webinar. I’m Katherine Banwell, your host for today’s program. Today, we’ll discuss how you can be proactive in your understanding of MPNs and work with your healthcare team to find the best MPN treatment path for you. Joining me today is Dr. Brady Stein. Thank you for joining us. Would you please introduce yourself?

Dr. Stein:                     

Hi, my name is Brady Stein. I’m a hematologist at Northwestern University in Chicago, and thanks very much for having me.

Katherine:                   

Before we begin, a reminder that this program is not a substitute for seeking medical advice. Please refer to your own healthcare team about what might be best for you. Dr. Stein, let’s start with the basics. The term “myeloproliferative neoplasms,” or MPNs, can be a bit confusing. Would you give us a brief overview of the classic types of MPNs? 

Dr. Stein:                     

Sure. So, there’s three classical types of MPNs that we focus on. These are the BCR-ABL-negative MPNs. So, what we’re referring to in this webinar is essential thrombocythemia, otherwise known as ET, polycythemia vera, often referred to as PV, and myelofibrosis, often referred to as MF, and myelofibrosis can exist on its own.

It can be primary, so a patient can start with that diagnosis, but it’s also important to note that patients who have ET or PV for long periods of time – they can head in the direction of myelofibrosis, so that’s kind of a secondary type of myelofibrosis, sometimes referred to as post-ET MF or post-PV MF. So, those are the three basic subtypes that we’re gonna speak about today.

Katherine:                    

Do symptoms vary for each type – ET, PV, and MF?

Dr. Stein:                     

They do. They vary, but they can overlap. So, oftentimes, ET is thought of as the more indolent of the MPN subtypes, but I think it’s pretty clear that patients with ET can have a similar burden of symptoms compared to patients who have polycythemia vera and myelofibrosis, so they exist on a spectrum, I think most to a degree that symptoms can be the most pronounced in patients with myelofibrosis, but not to undermine the symptom burden that can occur in ET and polycythemia vera.

Katherine:                   

Once a patient is diagnosed with MPN, what sort of testing should take place?

Dr. Stein:                     

So, the test that’s gonna lead to suspicion is gonna be a blood count, and that’s probably gonna be done in the primary care doctor’s office, so that’s gonna be the first suspicious test, and in general, there’s gonna be some abnormality. Myeloproliferative diseases are characterized in general by an overproduction of blood cells, so it’s going to be a higher white count, it’s going to be a high hemoglobin or hematocrit, or a high platelet count, or a combination of the three that’s generally gonna lead to suspicion.

Some patients may have pretty unremarkable blood counts and may present with a blood clot in an unusual location that could ultimately lead to the hematology referral. Some patients might have pretty unremarkable blood counts, but they might have palpation of their spleen, enlargement of their spleen in a physical examination. So, they’re generally the ways that patients are getting to the hematologist.

Katherine:                    

And, what about bone marrow biopsy?

Dr. Stein:                     

So, a bone marrow biopsy is a diagnostic test, and it’s generally recommended for all patients who have a myeloproliferative neoplasm either confirmed or suspected.

It’s advised in WHO criteria – World Health Organization criteria. PV can be made without a bone marrow biopsy – a diagnosis of PV – because it’s the most unique of the MPN subtypes. It’s the one that presents with a high hemoglobin.

So, that diagnosis can be straightforward at times for a hematologist when the setting is right, when there’s a high hemoglobin – or, high enough hemoglobin, I should say, a JAK2 mutation, which all patients with PV have that, or a subnormal erythropoietin level.

Oftentimes, we can make that diagnosis without a bone marrow, and the bone marrow becomes more prognostic. ET, a bone marrow is necessary for diagnosis, and myelofibrosis, you can’t make a diagnosis without it.

Katherine:                   

What do the results of these tests tell us about prognosis and treatment choices?

Dr. Stein:                     

That’s a good question. The bone marrow can be diagnostic in the setting of ET and myelofibrosis. In the setting of polycythemia vera, it can be more prognostic. In general, when a bone marrow is done, 1). To confirm diagnosis, 2). To assess prognosis, what we’re looking for as prognostic features are generally the degree of fibrosis or scarring.

So, each of the MPNs can have that. Of course, MF is characterized by the most pronounced scarring. It can happen to a more subtle degree in ET and PV. That’s gonna be prognostic in the setting of ET or PV. The pathologist will alert us about immature cells called blasts. We basically never see them at diagnosis in patients with ET or PV. We can see them rise in patients with myelofibrosis at diagnosis or through the course of follow-up. So, that’s prognostic.

All bone marrows generally have a chromosome analysis that’s called cytogenetics, and so, if there’s an abnormality, that can help place the patient’s prognosis into different risk categories. And then, nowadays, more so in myelofibrosis than any of the others, there are extended panels done. These are called NGS, or next-generation sequencing, kind of looking at mutations in a greater degree of detail.

So, not just what we call main mutations – JAK2, calreticulin, or MPL. These are looking at additional mutations that basically hold prognostic significance.

These are pretty well defined, and I think more important in MF compared to the other subtypes.

Katherine:                   

Would you explain the driver mutations in MPNs? What are they, and how they – or, what they mean for patients?

Dr. Stein:                     

So, there’s three of what we call driver mutations, and the most common is JAK2V617F, the next most common is calreticulin, and the least common or most rare is a mutation of MPL, the thrombopoietin receptor. So, the driver gene mutations are the three that we assess to help with diagnosis, and the prevalence varies. In ET, about 60% have JAK2, 25% have calreticulin, 5-10% have MPL.

In PV, 99% have some type of JAK2 mutation, and in MF, the situation is a lot like ET – 60% JAK2, 25% calreticulin, about 5-10% MPL. So, the driver mutations – we think of those as the genetic abnormalities that really drive the disease. They’re the main ones we can test for in a diagnostic setting.

I refer to them as the – to a patient, what I’m describing is you have a car, and the driver mutation is the one that’s sort of driving the car, and it’s doing it somewhat recklessly. It’s in the front seat, driving. And, along the way, the driver can pick up hitchhikers, which we should never do. I refer to those other mutations that are found by NGS as hitchhiker mutations that sit in the back seat, cause trouble, and really shouldn’t be there. They’re not the driver, they’re not fully responsible for the disease, but they can make it a bit worse.

Katherine:                   

We have a question from the audience, Dr. Stein. “I was recently diagnosed with MF, and I’ve had a bone marrow biopsy. How often will I need to undergo this procedure?”

Dr. Stein:                     

That’s a really good question. It’s a very important, very common question. So, the first bone marrow biopsy is diagnostic. The second bone marrow biopsy – or third – are generally reactive, meaning we don’t schedule them year to year unless there’s a change. We do them in a reactive way. If there’s something about the condition that’s changing – for example, if we suspect or worry about a progression – that’s when we would do the second bone marrow biopsy. So, we don’t set a determined frequency if the condition or the course is stable.

Katherine:                   

Dr. Stein, I understand that therapy is different for each of the MPNs. What do you take into consideration to help guide the treatment choice?

Dr. Stein:                     

So, that’s a good question. It’s gonna require maybe a little bit of a longer answer. It’s fairly nuanced. The treatment of ET and PV – right now, the goals are – the treatment is largely based on a patient’s vascular risk. That’s largely what influences the choice of therapy. And so if a patient has a perceived high risk for vascular complication in ET or PV, that’s when we’re gonna be a little bit more aggressive – so, more aggressive than watchful waiting, more aggressive than using aspirin alone, more aggressive than using phlebotomy and aspirin alone in polycythemia vera.

So, if the patient has a higher vascular risk, in general, we’re gonna need to do something more than what we consider to be the standard, and that’s where we enter into the question of cytoreductive therapy – therapies designed to lower blood counts apart from phlebotomy.

Maybe that’s gonna change. I hope it will change. Right now, the therapy for ET and PV is generally reactive. We either predict high risk and react, or if a patient is lower risk, if something changes – God forbid there’s a blood clotting event – then we may react to it.

So, ET and PV treatment are generally more reactive. In myelofibrosis, certainly, there are patients who can have lower risk and minimal systems, and there are some patients who can be observed with watchful waiting for sure, but more patients are symptomatic, more patients are gonna need therapy in myelofibrosis, and there’s sort of two big categories of therapy.

One is the risk-adapted, deciding if the patient is eligible and should consider stem cell transplant versus thinking only about medical therapy in a patient that may be transplant-ineligible.

And, the medical therapy is based on the worst symptoms for the patient. Is the symptom that’s the worst the spleen enlargement? Is it excessive fatigue? Is it weight loss, or inflammation, or fevers? If it’s that category of symptoms, we have a set of therapies. If it’s really the anemia that is the most problematic issue, then we follow a paradigm to treat anemia.

Katherine:                   

What about considerations like the patient’s health, age, genetic markers, things like that?

Dr. Stein:                     

So, of course. The comorbid illnesses can influence therapy choices, so if a patient is older and has other medical conditions, they’re not gonna be treated as aggressively.

So, in myelofibrosis, if a patient is older, with other medical illnesses, then it may be inappropriate to consider something like stem cell transplant, for sure. So, age and health comorbidities are highly influential. In terms of genetic features, if you’re asking about things like the type of mutation that a patient has, right now, we’re – in terms of vascular risk, for ET, the type of mutation matters for blood clotting risk, so if patients have different mutations, it could be treated differently. In other subtypes, like PV or myelofibrosis, in general, there’s – the mutation can be prognostic, but it may not be – it may not lead to a precise and distinct therapy just yet.

Katherine:                   

All right. What do you feel is the patient’s role in the decision for therapy?

Dr. Stein:                     

I think it’s a really important role. I think historically – and, this is decades past; this era should be well over and behind us – this era of authoritative medicine is over.

You can’t just have a doctor walk in the room and say, “This is your treatment, this is what you should do, I’ll see you later.” It’s shared decision-making, and that can be troubling for some patients. But, the idea of shared decision-making is us explaining options informing the patient and making decisions together. That’s really the paradigm for modern contemporary medicine.

Some patients have a harder time with that. A lot of patients say, “Well, doc, this is too overwhelming for me. I just want you to decide for me.” And, we try not to do that. That’s a more uncomfortable type of visit for me when a patient is very deferential and says, “Whatever you say, I’ll do.” That’s not really what we wanna hear. I wanna know that you feel really informed, that you have a good understanding because each of these treatments – any treatment, any medication has its pros and cons.

There’s no real magic bullets, and each upside has an equal downside, so you have to engage and open a dialogue, and what that means is that patients need to read and learn. That’s hard, but patients need to become proactive in their approach to their own illness, and all the patients who are listening now are doing that, trying to get more education about your relatively rare illness that’s gonna give you a much better framework to help make decisions together.

Katherine:                   

Absolutely. If a patient isn’t feeling confident with their treatment plan or their care, do you recommend that they maybe consider a second opinion or seek a specialist?

Dr. Stein:                     

Of course, yeah. These are rare diseases, and patients often – I would say that in my clinic, a lot of the patients direct their own second opinions. Oftentimes, it’s coming from the patient more so than their doctor. I think the patient community is very active, the patients are networking, and they’re finding the right specialist to get to.

I think it should be really a team approach. It’s never – it’s usually not very convenient to go to a university unless you live really close, so you wanna have someone close to home who can handle the routine, and then, someone who maybe is a little bit further away who can see you once a year, can help with the big decisions, can be part of the healthcare team. So, we generally recommend that you have someone near, and that maybe you have someone far who focuses only on MPNs as part of your team, and now, it’s a little different. Telemedicine is becoming a pretty ingrained part of medicine. It’s a little easier to have those visits with a physician who’s far away because of telemedicine.

Katherine:                    

So, now that we’ve discussed how a treatment path is determined, can you walk us through the currently available MPN treatment approaches and who they might be right for?

Let’s start with essential thrombocythemia, or ET.

Dr. Stein:                     

So, I think the first thing is taking an inventory of symptoms, seeing how symptomatic the patient might be. Again, there are some patients who are asymptomatic or have few symptoms, and they were told of a high platelet count during a routine visit, so some patients can be observed if they have few symptoms, and especially if they fall into a lower vascular risk category.

So, symptom assessment first. Second, looking at vascular risk, and there’s four categories of risk in in ET in terms of predicting the likelihood of a future blood clotting event. There’s a very low, low, intermediate and high risk group, and that’s based on a patient’s age, whether they’ve had a blood clot before, and the type of mutation they have. JAK2 mutations increase the risk of clotting.

So, if a patient falls into a higher-risk group – say they’re older than 60 with a JAK2 mutation or they’ve had a prior blood clot – those are patients who are generally treated more aggressively with cytoreduction. And then, the other thing is aspirin. We often see aspirin given to all patients with ET, but not all patients with ET necessarily need it. The role of aspirin is actually a little less clear in ET. For a very low-risk patient, there’s a potential for more harm than benefit, especially if the patient lacks a JAK2 mutation. So, the evidence base to support aspirin for all ET patients is just not there; it’s evolving.

Katherine:                    

What about polycythemia vera, or PV?

Dr. Stein:                     

So, there’s a few standards. It’s different – the aspirin question in PV is generally answered by randomized data from 16 years ago in 2004. It’s been shown that aspirin reduces the risk of clotting in PV patients, so, generally, we give low-dose aspirin to all patients.

And, hematocrit control is really important. At least, a goal of 45% is mandated in PV. And then, there are patients who might fall into a higher-risk category – older than 60 or have had a prior blood clot – they need something more. And then, I’d also emphasize that there are lower-risk patients who may not be traditional candidates for cytoreduction, but they could have symptoms that really interfere with quality of life, and symptoms alone can be the trigger to add something more to the phlebotomy and aspirin program.

Katherine:                   

What about things like interferon?

Dr. Stein:                     

So, interferons have been used in MPNs for decades and decades. So, a longstanding history with interferons. The issue has been tolerability.

These days, there’s a class called pegylated interferon that’s longer acting, and I think there’s been a lot more use, at least in the last 10 years, still much more in an academic setting than a community practice.

But, interferons have a pretty established role in MPNs, especially polycythemia vera, for sure in ET, less so in myelofibrosis.

Katherine:                    

Dr. Stein, you mentioned high-risk versus low-risk patients quite a bit. How is that risk determined?

Dr. Stein:                     

So, it’s different for each subtype. For ET and PV, when we talk about high versus low risk, we’re talking about vascular complications, risk of having a blood clot. We’re not really talking about risk of transformation. We don’t have, I think, wonderful, widely used toolkits to predict those things. We know they can happen, but our treatment is still really based on clotting for ET and PV.

And, MF – each couple of years, the tools that are available to assess prognosis become more and more. So, in MF, we’re using the most comprehensive approach – of course, taking into account things like age and demographics, but also, looking at symptoms, looking at the depth and severity of blood count changes, looking at bone marrow features like the degree of scarring, looking at the rise in blast counts, and then, looking at chromosomes and novel genetic markers. So, we’re definitely the most comprehensive in myelofibrosis at assessing prognosis.

Katherine:                   

How do clinical trials fit into treatment choices?

Dr. Stein:                     

Clinical trials are always a treatment – always an option for patients with myeloproliferative neoplasms because while we have some standards, we can definitely improve upon those standards for certain. So, clinical trials are always a therapeutic option. I think the one thing is that it may not – it’s not always the most convenient option, but it could be a really important option if available to you.

So, clinical trials basically offer something new or novel that would not otherwise be available to other patients. So, ruxolitinib was approved around 2011, but the first clinical trials were in 2007, so that’s the example I give to a patient about the benefit of a clinical trial.

The patient can get access to a drug that’s effective perhaps three to four years before it’s commercially available.

That’s really the biggest advantage, is you can get early access to something that could really help you. The downsides are that clinical trials are not usually as convenient as regular care, there’s often more visits, and there’s a lot of unknowns – unknowns about whether it will work. Some side effects are known and expected; there are others that are unknown. So, it’s a lot to think about, but I think it’s always important to consider, especially if your first-line therapy has not been effective, if it’s losing its touch, it’s a good thing to think about for a second line.

Katherine:                   

Are there emerging approaches for treating MPNs that patients should know about?

Dr. Stein:                     

Yeah, absolutely. I think the first question – I think patients are often worried that they have a really rare disease, and why would anyone do research in this area, and that’s – the research community is extremely engaged, the productivity is pretty impressive, and there’s a lot of clinical trials in the space, and I think what I try to explain is pharmaceutical companies aren’t just targeting the most common diseases.

They have interests in rare diseases, and findings in rare diseases can be extrapolated to other diseases that you might think are unrelated, but they can share features, so when you find something working in one space, it can have broad applicability. So, there’s an abundance of research in myeloproliferative neoplasms which are emerging?

In PV, I think there’s quite a possibility that there’ll be a drug approval in 2021, a novel type of interferon called ropeginterferon.

That is a drug that’s approved abroad; it’s approved in Europe, and I believe it’s approved in Taiwan, and the FDA is looking at it now. So, it’s a possibility that there’ll be a future option for patients with polycythemia vera. So, yes, it’s research now, but it could be available, and so, that’s the drug that I’m starting to talk more and more about for patients with PV.

In myelofibrosis, you have two JAK inhibitors that are approved, ruxolitinib and fedratinib, you have two others in clinical testing, momelotinib and pacritinib, and then you have a whole other class of what we call non-JAK2 type of therapies targeting the vast array of pathway abnormalities in myelofibrosis.

So, there’s a number of different clinical trial options, especially in myelofibrosis. I think that’s the disease area where there’s the most clinical trials.

Katherine:                   

Once a patient has started treatment, how do you know it’s working?

Dr. Stein:                     

That’s a good question because this is a very unique area. Yes, of course, in some respects, it’s straightforward with ET or PV. If we’re starting a medication to control a blood count in hopes of having lowered the thrombosis risk, you can look objectively at blood counts.

Okay, your hematocrit is at this goal? Yes, therapy’s working. You have not had a blood clot? Yes, therapy’s working. So, there are some objective things. In myelofibrosis, there are some objective things like measuring the spleen and seeing it reduce. You can feel that with your hands, or you can do an ultrasound. So, there are some objective parameters of success. But, in this area, patient-reported outcomes are really important, and so, a measure of success is really just asking the patient, “Do you feel like your drug is working? Do you feel better?”

It’s kind of a simple question, but it’s really important, and it’s what we ask in patients who are on certain therapies. “Do you feel like the net effect of your therapy is still positive? Do you feel like it’s helping?” Seems like a straightforward type of question, but I think the answer is extremely informative. When a patient says, “Yes, definitely, my medication is still helping me,” then I know that I don’t need to change it.

Katherine:                   

Right. Patients are often concerned about progression in MPNs. Would you explain the progression of MPN and the indicators that one might be progressing?

Dr. Stein:                     

So, I think the important but hard thing to know about MPNs is that they’re chronic progressive illnesses, but what we don’t know in an individual is how long it’ll take to progress. Is the ET or PV gonna progress in 10 years, 25 years, or 35 years? Those are difficult things to predict. And, MF is progressive as well. I think it’s a little easier to identify those patients who may progress more rapidly compared to more slowly.

So, MPNs progress, and that’s the first important thing, is that they’re chronic illnesses and patients have to be aware that they can change. ET and PV can move to myelofibrosis, and when that happens, generally, symptoms change, the spleen enlarges, and blood counts change. We start to see anemia when we didn’t before.

And, when MF progresses, the symptom burden is one thing, maybe more fatigue, unexplained fevers, drenching sweats, or weight loss. On exam, measuring the spleen and seeing it get larger, seeing a fall in the platelet count, a need for red cell transfusions or a rise in the blast count. Those are all features that we’re looking for that can indicate a progression.

Katherine:                   

Let’s talk about patient self-advocacy now, Dr. Stein. Patients can sometimes feel like they’re bothering their healthcare team with their comments and questions.

Why is it important for patients to speak up when it comes to symptoms and side effects?

Dr. Stein:                     

I smile a little bit because patients – I get a lot of patient emails by MyChart. That’s our medical record, and it’s a secure patient email, and a lot of patients will start their message by saying, “I’m sorry to bother you.”

And, I always say, “Why do you think that? It’s my job. Please don’t apologize for reaching out to me.” So, that’s kind of the first thing. Don’t feel like you’re bothering your doctor. There are certain things that we won’t know unless you tell us, and so, I think that’s pretty clear. When we’re in a patient room and there might be a husband and wife together, and whether it’s the husband is the patient or the wife is the patient, we might ask a question, and we might get, “No, everything is fine,” but all doctors kind of sneak over to the partner, and the partner may be saying – they’re making gestures to us. There may be nonverbal forms of communication to tell us there’s something much worse than what the patient is telling you.

So, again, “advocate” meaning you have to tell us what’s going on with you. If you’re worried about something, please don’t be stoic about it. These diseases are treated a lot based on your symptoms, and so, if you don’t tell uls about your symptoms, we won’t know.

And, in terms of advocacy, I think one of the things is that these are pretty rare diseases. In an academic center, no, this is our focus, but if you’re in a community practice where the doctor’s seeing 10-15 different things during the course of a day, it’s basically impossible to keep up with myelofibrosis, especially if you have one patient in your whole practice. I can’t do that for diseases that I see that I have only one patient. The medical literature can be overwhelming.

So, patients can quickly outpace their doctor in terms of their knowledge of these diseases, but I think it’s really important to read, to learn, and to think about the illness because you may find out things through your research that your doctor wouldn’t know are available. You may find a clinical trial, a new strategy, or a new test that they simply haven’t had the time to keep up with or learn about. So, that’s what advocacy is about. Reading is really important, but you have to find a balance. I want my patients reading, but you’ve gotta find the right amount because there’s a certain amount of reading where the patients start to get overwhelmed.

All patients kind of get to this point. They take it in – like taking it in like a fire hydrant in the beginning of the disease, and it’s overwhelming, and then they start to find their balance. I think there’s a point where the reading becomes anxiety-provoking rather than ameliorating anxiety, and all patients just generally find their balance.

What I also say is if you read something that alarms you, write to me, write to us, and let us verify that because there’s a lot out there, and I think the patient communities are a phenomenal form of support, but there’s a lot of patients giving advice to each other, and sometimes that needs to be double-check – or, always, it needs to be double-checked by another doctor because sometimes, the advice is simply not – may be very individualized or not generalizable, or sometimes it’s simply inaccurate.

Katherine:                   

What would you like to leave the audience with? Are you hopeful?

Dr. Stein:                     

Oh, of course. Of course, I’m hopeful. What I leave the audience with is that things are changing; things are changing for the better, and the therapeutic choices in three years could be entirely different. I think there’s progress. Progress in medicine – some patients feel it, it’s slow, but having been in this field for a decade, there’s more and more therapeutic options emerging. Kind of what I’m looking to see most, honestly – I’m following everything really closely, but what I’m starting to think about more is paradigm shifts.

What I’d like to see in the field is to move away from a reactive type of approach and think more about early initiations of therapy, more of a proactive type of strategy, not really – because when we talk about therapeutic choices with a patient and the patient says to us – we don’t say it like this, but the way they say it back to us is, “So, wait, we’re gonna wait for something bad to happen, and then we’ll start treatment?”

I think that – I share discomfort, as – I’m uncomfortable with that approach. The reason we haven’t been proactive is because we’re kind of waiting for highly safe, highly effective therapies that could potentially change the course of the illness. That’s why we have been reserving our therapies, and that’s why our secrets sometimes include less aggressive watchful waiting with later initiation of therapy just because physicians haven’t been satisfied with their choices, but I’m hopeful that that’ll change.

Katherine:                   

Dr. Stein, thank you for joining us today.

Dr. Stein:                     

Thank you very much for having 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 joining us.

What You Should Know About Progression in MPNs

What You Should Know About Progression in MPNs from Patient Empowerment Network on Vimeo

Dr. Srdan Verstovsek provides an overview of myeloproliferative neoplasm (MPN) progression and reviews indicators that essential thrombocythemia (ET), polycythemia vera (PV) or myelofibrosis may progress.

Dr. Srdan Verstovsek is Chief of the Section for Myeloproliferative Neoplasms in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Verstovsek, here.

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Transcript:

Dr. Srdan Verstovsek:

When we talk about ET and PV, they should be life-long conditions without much of a change. It’s uncontrolled blood cell count and thromboembolic events, which are then subject to a therapy, and the goal of therapy is to decrease the thromboembolic risk.

There is still, in some smaller proportion of the patients, a risk of a disease change on its own. We talk about the genetic testing that can reveal a change in genetic complexity of the disease, which may be responsible for a change down the road. Or abnormalities in chromosomes that can be seen at the time of diagnosis in some of the patients with ET and PV, not very often, which may predispose patients to a change down the road, a change to more aggressive condition.

So, a smaller proportion of the patients, perhaps 10 – 20 percent of the patients between ET and PV, can over time, long time, acquire fibers in the bone marrow.

That can lead to anemia actually, progressive increases in spleen, bone marrow cells in blood, that would be then a change to myelofibrosis. And a very small percent of the patients actually can change to acute myeloid leukemia, with the baby cells in the blood and the bone marrow, these are called blasts.

They should not be in the blood in the wrong person. They should be below 5 percent in bone marrow in normal person, but if they go above 20 percent, we call that acute leukemia.

So, transformation of ET or PV to myelofibrosis or acute myeloid leukemia, are fear, and obviously can lead to a shorter life expectancy. And so, one can certainly worry about that, but again, it is in a smaller proportion of the patients, and we don’t usually worry that much about it. However, the worry does exist, that’s why you are asking me about it, and the problem is we don’t have medication that would be known and proven in prevention of that biological change of the disease in some patients.

In myelofibrosis it’s similar situation, 20 – 25 percent of the patients change to acute myeloid leukemia, and we don’t have real medication that would be preventing that change.

Promising ET, PV & Myelofibrosis Therapies in Development

Promising ET, PV & Myelofibrosis Therapies in Development from Patient Empowerment Network on Vimeo

MPN specialist, Dr. Srdan Verstovsek discusses the latest research and progress for the treatment of patients with essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF).

Dr. Srdan Verstovsek is Chief of the Section for Myeloproliferative Neoplasms in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Verstovsek, here.

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MPN Treatment: Why Testing for Mutations Matters

 

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Transcript:

Dr. Srdan Verstovsek

When we talk about the new therapies in development, there are many in myelofibrosis in particular, and a few are in essential thrombocythemia and polycythemia vera. Let’s start with ET and PV. Here we are expecting either studies, or possibly even approval, of a long-acting interferon called Ropeginterferon that was approved a year ago in Europe for PV patients.

We gonna have, hopefully here in the United States, that drug for our patients in a year or perhaps studies in PV, or perhaps most definitely, I would say, studies in ET with this drug. That would be enhancement of what we done off-label using interferons that are approved for some other conditions. We know that interferons are biological agents active in these conditions to control the bone marrow, and perhaps even decrease the number of malignant cells in the bone marrow of patients with ET and PV, which may be beneficial down the road.

In myelofibrosis, the picture is completely different. In this setting, the life expectancy, unfortunately, is affected as we discussed, and we need therapy that would be perhaps improving that life longevity. As we know, the ruxolitinib JAK inhibitor that has been around for nine years can extend the life a few years, but not cure people.

So, helping JAK inhibitors by combinations with other active agents that would be biologically modifying that bone marrow, decrease the tumor burden, improving the quality of life or anemia, are at forefront of what is happening right now. So, combinations with Navitoclax which is Bcl-xL cell inhibitor, CPI-0610, which is BET inhibitor, Luspatercept which is anemia drug.

These are phase three studies that are planned to start soon for possible approval for combinations over JAK inhibitor alone for different problems that people face.

Or, later on in the course of the disease, JAK inhibitor may fail. What do you do then? So, we have studies announced that will be done in what we call a second line, after-JAK inhibitor. And the MDM2 inhibitor was announced. Imetelstat inhibitor in the second line. Momelotinib JAK inhibitor in the second line. Fedratinib is being studied, another JAK inhibitor. Pacritinib for patients with low platelets

These are all phase three studies. That’s means for approval of this drug, so that will be three and four, seven different phase three for myelofibrosis patients with different clinical scenarios, different clinical problems are being done, or about to be done, in very near future. So, my prospect is here. My view on that is that we will have, hopefully, at least some of these seven studies leading to approval of some new drugs for our patients with myelofibrosis.

Monitoring MPNs: When is it Time to Switch Therapies?

Monitoring MPNs: When is it Time to Switch Therapies? from Patient Empowerment Network on Vimeo

MPN expert, Dr. Srdan Verstovsek reviews factors that may indicate a treatment change for patients with essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF).

Dr. Srdan Verstovsek is Chief of the Section for Myeloproliferative Neoplasms in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Verstovsek, here.

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Transcript:

Dr. Srdan Verstovsek

The real definitions of a failure of a given therapy, it’s not easy to come by. Experts in the field, doctors that see a lot of myeloproliferative neoplasm patients, occasionally get together and try to put in place some guidelines. What would be a failure to a therapy mean for patients with ET or PV?

Would that be, for example, polycythemia vera patients too many phlebotomies when you are on hydroxyurea.

Hydroxyurea is a chemotherapy by mouth, should be eliminating need for phlebotomy, should decrease the white cells and platelets, and the spleen enlarged, and improve the quality of life.

If that’s not possible, and you have to define what that means, then you would say, you should change. So, guidelines do exist, which are always used in clinical studies to define the failure and justify a change. But they should also be applied in clinical practice to apply possible.

If you are on hydroxyurea for ET and PV, and you are not controlling blood cell count very well, you can’t take more because there are side effects from hydroxyurea, you should change. Right?

If you see a progression of the spleen, or worsening of quality of life despite the control of the blood cell count, something is wrong, maybe you should change.

In myelofibrosis is similar situation. You may be experiencing a good therapy on JAK inhibitor or anemia medication, but then after a while, spleen starts to grow, quality of worsens, or anemia develops, then you should change.

It’s not as easy to see exactly to define, but you get the point I’m sure because people are different, the benefit extent or benefit is different, pattern of a failure is different, and we have a lot of difficulties in really objectifying what this means to fail.

My approach is when I see a failure developing – nothing happens overnight. You try to modify what you do by adding another medication, adding medications for whatever is causing that failure, or modifying what you’re doing by changing the schedule or the dose. So, not to give up and say, “Oh, it’s not working,” but trying to work with the patient, and with the medications that you have in different way, for benefit to last the longest possible. 

Which MPN Treatment is Right for You? Factors to Consider

Which MPN Treatment is Right for You? Factors to Consider from Patient Empowerment Network on Vimeo.

Dr. Srdan Verstovsek, discusses how multiple factors, including diagnosis and symptom burden, determine which MPN treatment path may help improve a patient’s outcome.

Dr. Srdan Verstovsek is Chief of the Section for Myeloproliferative Neoplasms in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Verstovsek, here.

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Transcript:

Dr. Srdan Verstovsek

So, we talk about diagnosis, and then prognosis, and then go over [stem cell] transplant. Now, the transplant is done in only less than 10 percent of the patients because most of the patients are elderly. That’s why you have the disease.

They might not have a donor. They may be sick. There are multiple reasons, so transplant happens in less than 10 percent of the patients. Once we are over that, you say, “What’s wrong with the patient?” Not wrong in terms of dying, but do you have a significant anemia? Do you have an enlarged spleen? Do you have a bad quality of life when we talk about myelofibrosis? All of this that I have talked so far, applies to myelofibrosis. These are the three main reasons for initiating of therapy, usually. Significant anemia, significant bad quality of life, and significant symptom related to the big spleen. You would then introduce therapies.

For the splenic symptoms, we usually prescribe JAK inhibitors. That would be standard practice. For anemia, we have medications from injections under the skin, to some pills. No real approved therapy for anemia, but whatever we can do help patients counteract those problems because slowly over time they’ll get worse and worse, and people die with myelofibrosis between five and seven years.

So, we wanna combine medications. We’re gonna introduce medications as soon as something wrong with the patients to improve whatever is wrong so that the quality of life can continue at a decent level.

Let me go back a little bit to essential thrombocythemia and polycythemia vera, ET and PV. These two conditions are considered rather benign. They should not much effect the longevity, perhaps PV can. And if they do, the main reason for dying from ET and PV is the blood clot or thrombotic event.

This is what we say, usually. A blood clot or some bleeding usually clots in the heart, or the brain, or the lungs, can kill the person. So, we don’t usually talk about the life expectancy in terms of genetic mutations, or abnormalities in chromosomes, or something that will kill the patient outside of the blood clotting risk.

So, what we are talking about then, is after diagnosis, we are talking about the prognosis, when we talk about ET and PV, prognosis is related to what’s your thrombotic risk? So, we talk to patients with ET and PV about thrombotic risk assessment.

And typically, age over 60, or having a history of blood clot, we’ll say yes that patient is a high risk patient with ET, or high risk patient with PV, for the blood clot. And we will be treating patients for that risk in different ways.

So, it’s a little bit different angle here on what we try to achieve in ET and PV patients. More benign, more chronic, assessment of the risk of clotting and control the blood count, and occasionally when we need, control the spleen symptoms. But different ballgame and ballpark then the myelofibrosis part.  

There are, obviously, standard practice protocols in terms of what do you do? Right? So, if we are talking about ET and PV, you would say, if you are – as your remember now, we divide patients in those with the low risk of blood clot, and high risk for blood clot. For low risk, we just give people baby aspirin, and if they have PV, we phlebotomize the patients, blood-letting.

So, not much experimentation there. But there are studies that one can join if there are too many phlebotomies, for example, too many blood-letting episodes. And there are studies with medications that would be decreasing that need completely.

There are also studies in patients that are high risk for blood clotting, which typically would be treated with hydroxyurea, chemotherapy by mouth.

There are new versions of the interferons, biological agents given under the skin every two weeks, that would perhaps be taken instead of a standard practice hydroxyurea.

Not too many studies in ET and PV, really. Some. But in myelofibrosis, there are many because with ruxolitinib, for example, which has been around for about nine years, it’s a JAK inhibitor, you get in many patients good control of the splenic symptoms, but it does not last forever, and in some patients, it may benefit to some degree, but not completely.

So, there are many studies where you can add another medication to ruxolitnib a JAK inhibitor, to boost what it does more of the splenic symptoms controlled, or to add another benefit. The JAK inhibitors do not, by and large, improve the anemia, so how about adding anemia drug to ruxolitnib.

So, combination studies are many underway, so you can actually enroll – even with the newly diagnosed myelofibrosis patients, in the need of therapy, in a clinical study. Not to say, after JAK inhibitors in a second line. That’s what we call it. After JAK inhibitors you need to do something else, that second line, there are many studies because there is no other approved therapy. So, for myelofibrosis, no question in my mind, there are so many studies underway, you can be participant in study to get your result boosted by whatever else is added to what you’re doing, and discover for the large population of patients, novel therapies. 

Could an MPN Clinical Trial Be Right for You?

Could an MPN Clinical Trial Be Right for You? from Patient Empowerment Network on Vimeo.

Is a clinical trial your best MPN treatment option? Dr. Ruben Mesa explains the clinical trial process and how patients may benefit from participating.

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

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Transcript:

Dr. Ruben Mesa:

There is much exciting research in myeloproliferative neoplasms. First, research trying to understand, why do people develop MPNs, and why do they progress. This is crucial research, and that this basic research to better understand the diseases will help us asses whether our treatments are having an impact slowing down the progression of the disease, and help us better design therapies that, hopefully, can cure these diseases.

Be reassured  that our goal as a scientific community is to cure the MPNs. Now, until we’re able to do that, we want to be able to best control them as best we can. So, the next level of research is really in new therapies; primarily drug-based therapies, but future therapies using the immune system; potentially using vaccine therapy to try to better control the disease to make the disease as neutral in your life as possible.

Our goal, short of curing the disease is to make the disease as invisible in your life as possible. Hopefully, minimal side effects, minimal symptoms, protected against risk of blood clots or bleeding, ideally, decreasing the risk of progression, and hopefully without any significant side effects from the medication your receiving.

So, that really is our goal.

 Clinical trials are a crucial way for us to improve the treatments that we have for any diseases. And in particular, in areas like myeloproliferative neoplasms where we have therapies, but we don’t have cures, clinical trials are crucial. Clinical trials are a structured way for you to be able to receive a new treatment. That treatment is closely monitored, and starts with a strong belief that that treatment is going to be beneficial for you.

Being on a clinical trial has many steps, but you are in the driver seat in each of them. So, you’re able to enroll in a study, and you’re able to decide at any point whether or not you’d like to continue on in that study. You are made clearly aware of what you’re receiving; what dose; what to expect at each and every step of that therapy.

It’s a treatment just like any other, but we use them because we are hoping that it will be better than the treatments that we have, and we do it on a clinical trial so that we can learn from that experience. If that drug is better, then we should probably expand its use and give it to other people, and have it be approved and used around the world. Or for whatever reason that therapy is not as helpful as we would like, then we learn from that, as well.

Why was it not helpful? Was it the wrong therapy? Was it targeting the wrong aspect of the disease? Were there side effects that made the therapy not beneficial? So, we learn a lot about it in either direction. Hopefully, individuals who participate in clinical trials will have a direct benefit themselves by being able to experience a new therapy that is, hopefully, better. But also, they do have the ability to help other patients now and in the future that will be facing the same disease they have.

MPN Treatment Decisions: Which Path is Best for You?

MPN Treatment Decisions: Which Path is Best for You? from Patient Empowerment Network on Vimeo.

Dr. Ruben Mesa provides an overview of available treatments and reviews important factors to consider when choosing a therapy for essential thrombocythemia (ET), polycythemia vera (PV) or myelofibrosis (MF).

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

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Transcript:

Dr. Ruben Mesa:

The treatment landscape for myeloproliferative neoplasms is changing very rapidly. And in a good way, it’s increasingly having many more options for patients with Myeloproliferative Neoplasms. But I would separate it, really, into two groups. First, there are those individuals with essential thrombocythemia and polycythemia vera.

These individuals, we have newer therapies, such as interferons, we have, potentially, use of JAK inhibitors, we have some experimental therapies, as well as prior therapies we’ve used and become accustomed to, including hydroxyurea, phlebotomy, and aspirin.

But we’re learning much more about how to use these therapies; how to combine them; what constitutes success with these therapies; what should constitute a change in terms of therapy.

And there are new therapies being developed in the future that will impact this group of individuals with earlier MPNs: ET and PV.

For patients with myelofibrosis, the treatment is evolving. Patients with Myelofibrosis are affected in different ways. It is, in some ways, a more problematic disease.

There is evolution of our most impactful therapy, of stem cell transplantation. We have a better sense of in which patients we should consider that treatment, and how that can be applied in the safest way. We also have more medical treatments. We just saw in 2019 the approval of Fedratinib as the second specific JAK inhibitor approved for patients with myelofibrosis.

We, additionally, now have, truly dozens of clinical trials of new therapies in development that are in clinical trials right now that might be helpful for patients with myelofibrosis who have either had Ruxolitinib, or have a suboptimal response to Ruxolitinib, or sometimes even newly diagnosed patients. But I would say the future is very bright.

So, it is key with a treatment to first understand what is the treatment, what is the dose, and what is the goal? Each of the treatments have different goals. Some of the goals are to decrease the likelihood of blood clots or bleeding.

And frequently, we assess whether we’re protecting against the blood clots or bleeding by bringing down elevated counts. Is the plate account high, and we’re trying to bring it into the normal range? Is the hematocrit high, and we’re trying to bring that to under 45%? Is the white blood cell count high? Have we lowered each of those? First, it’s around controlling blood counts if that is the goal, as well as trying to decrease at risk of blood clots or bleeding.

 Second, if patients have symptoms associated with their MPN, sometimes itching, sometimes symptoms associated with high courts, sometimes enlargement of the spleen, or symptoms associated with the spleen, have we reduced or nullified those symptoms? Have we shrunk the spleen if the spleen was enlarged?

And then, finally, we assess our goal by trying to be sure that patients are not progressing or getting worse on the disease. So, depending upon the treatment, we first asses what is our goal? Is it to improve counts? Is it to improve symptoms? Is it to shrink the spleen? And have we accomplished one, two, or all three of those goals? Or was only one those our goals to begin with?