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How to Play an Active Role in Your MPN Treatment and Care Decisions

How to Play an Active Role in Your MPN Treatment and Care Decisions from Patient Empowerment Network on Vimeo.

How can you play a role in your MPN care and treatment decisions? Engaging with your healthcare team is essential and may lead to better overall outcomes. In this program, Dr. Naveen Pemmaraju provides tips for how best to advocate for yourself or a loved one, as well as tools for making treatment and care decisions.

Dr. Naveen Pemmaraju is Director of the Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Program in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Pemmaraju, 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 explore how to engage with your healthcare team when diagnosed with a myeloproliferative neoplasm, and we’ll discuss the patient’s role in care decisions.

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 today. Joining me is Dr. Naveen Pemmaraju. Dr. Pemmaraju, would you please introduce yourself?

Dr. Pemmaraju:         

Well, thank you for having me, Katherine and team. I’m Dr. Naveen Pemmaraju. Associate Professor of Leukemia and the Director of the Rare Disease Program with Blastic Neoplastic Cell Neoplasm (BPDCN) here at MD Anderson, and I’m happy to be here with you guys.

Katherine Banwell:    

Thank you so much. We’re glad to have you with us today. As we move through this conversation, we’ll talk about the classic myeloproliferative neoplasms: essential thrombocythemia, polycythemia vera, and myelofibrosis.

But before we get into our discussion, let’s start with the question that’s on the minds of many of our audience members. We’re all hearing that the COVID-19 vaccine is safe, but how effective is it for MPN patients?

Dr. Pemmaraju:         

Well, I believe that this is one of the most important issues of our time.

I think the way I would approach the COVID-19 question is, one, is we know that if our patients contract the virus, that can be deadly in actually many of our patients. So, I think it’s actually important to remember that the virus is still out there and that getting the virus is potentially very life-threatening, not only for the general population but for our patients.

For the vaccines, I kind of have two stories to tell you. So, one is my own anecdotal experience in the clinic where it has been surprisingly and remarkably well-tolerated in most of our patients. This is both the mRNA vaccines and as well as the J&J vaccine. And so, overall, we’ve seen a very minimal amount of allergic or other reactions.

I think the most important part, as you said at the top, is for specific medical advice, we need to be talking to our own providers. But I think for our MPN patients, we’re giving some caution, looking at the blood counts, what chemotherapy folks are on. But, in general, I’ve been happy with that rollout.

Now, for the effectiveness of them, sure. That’s a question of ongoing research. There are some data that’s coming out, particularly in CLL and other leukemias that – correct – maybe some of our immunocompromised patients, as you would expect, may not be able to mount the appropriate response. But all that data is moving and fluid, so we’ll see.

And then I think the other point here is with this question of the virus itself and maybe some of these vaccines having a signal for increased blood clots or coagulopathy.

This is something I think we have to follow in our MPN community only because our patients are already at a high risk for both bleeding and clotting. So, the virus itself, COVID-19, post-syndrome coagulopathy, possible side effects – idiosyncratic and rare, for sure, from these vaccines that can lead to a vaccine-induced thrombotic state. I think these are some of the factors that we have to watch out for. So, in general, we don’t yet know the exact answer for each patient, PV, ET, MF, how effective the vaccine may be. But we are encouraging everyone to go for it unless there’s an obvious contraindication. Katherine?

Katherine Banwell:    

Okay. Good. Thank you. Let’s learn a little bit more about the disease itself. Dr. Pemmaraju, do a level set with our audience. Can you help us understand the differences between ET, PV, and MF?

Dr. Pemmaraju:         

Yeah, this is very important because we toss these words around as if there’s some big definition that was given, and oftentimes, that never happens. So, let’s pause to do that. So, this goes back to the 1950s when William Dameshek, who really postulated the modern MPDs at that time as they were known – myeloproliferative disorders – really thought that there were four diseases that were similar at some level and then presented differently. So, that’s polycythemia vera, essential thrombocytosis, myelofibrosis, and CML, chronic myeloid leukemia.

Then, as the modern era comes in, CML is divided off because of the Philadelphia chromosome, BCR-ABL, which is present in 100 percent of those patients.

So, now we know CML is its own thing. And now we have the big three, sort of non-Philadelphia chromosome MPNs, as they’re now known, because neoplasm – cancer – instead of disorder. Within the subtype, and this is important, the subtypes that you mentioned are the most common.

So, polycythemia vera – poly meaning many, cythemia, cells, vera is Latin for true. This is the designation for the patient who has a higher than expected blood red cell mass or hematocrit. And it actually, interestingly, Katherine, most patients with p. vera have an increase in all three of their blood lines, so the red cells, hemoglobin, hematocrit, platelets, and white count. Those patients with PV are especially at risk for both bleeding and clotting, transformation to myelofibrosis, and even transformation to acute leukemia in maybe 5 to 7 percent of patients.

So, the usual treatment there, Katherine, is to bring off the blood mass. That’s the phlebotomy.  And then in the patient who is above the age of 60 or has a prior blood clot, to give some form of chemotherapy, hydroxyurea (Hydrea) or interferon, for example.

Now, the second grouping is ET, essential thrombocytosis. Again, this word vera or essential, meaning not reactive, not benign, not from a regular cause like a surgery or a trauma or an inflammation. So, it means a cancerous cause, an autonomous cause, something that’s coming on its own.

Thrombocythemia or thrombocytosis, meaning too many platelets. So, usually, patients with ET have too many platelets as their predominant manifestation. But again, as with p. vera, patients can get into problems with that. Very, very high platelets, usually a million and a half or higher, can actually lead to bleeding. Not necessarily clotting, but extra bleeding. And then patients with any platelet levels, because the platelet level doesn’t exactly correlate, can have either bleeding or clotting. So, that’s usually the predominant factor. And again, the underlying problem with these MPNs is that they can transform to the other ones – PV, MF, even acute leukemia.

And then, finally, myelofibrosis, which we could spend the whole hour on just by itself, is the more advanced state out of these.  So, it can either arise out of the PV or ET or stand alone. And really here, this is an advanced bone marrow failure state with bone marrow scarring or fibrosis. And now, usually, most patients, their blood counts, rather than high are now low because the bone marrow is unable to produce enough cells. And then, therefore, the sequela of the disease – anemia, thrombocytopenia. So, low blood, low platelets.

Then you need transfusions. The liver and the spleen get larger because they remember how to make blood cells. People can have a wasting away appearance. And then here, more than the PV or ET, this is more of an acute disease for many where if you have intermediate to high stage, these patients can transform more readily to leukemia and have a decreased overall survival.

Katherine Banwell:    

When a person is diagnosed with an MPN, they have a whole healthcare team. Who is typically on that team?

Dr. Pemmaraju:         

Well, it’s interesting. Yeah, that’s evolved over time.

It used to just be patient and their local oncologist, right? And the oncologist office has become a very busy place with mostly solid tumors. So, breast, prostate, colon, and then maybe a few scattered patients in most practices with blood cancers. Obviously, blood abnormalities are common with platelets and anemia and all that, but to actually have an MPN patient in the general hem/onc practice is actually quite rare. Right? These diseases are 4 to 5 out of 100,000 people.

Now, fast-forward to the modern era. I think this is important. I think now, what I personally encourage – and obviously I’m biased because I’m here at the academic center. But I really think that patients with rare blood cancers such as MPNs should be co-managed. So, be seen by your local hematologist/oncologist, for sure. They know you the best. But also have a referral, if you’re able to and have the resources and ability to travel, to an academic center where you can see a blood cancer specialist such as me or my colleagues, as I only focus on blood cancer.

So, I’m not seeing patients with a solid tumor. So, local oncologist. If you can have a blood cancer expert as part of your care, it doesn’t have to replace the care. And then to have a member of the nursing allied professions – nursing and APP, advanced practice providers – is really becoming essential to help with acquiring the prescriptions from the specialty pharmacy, prior authorizations, teaching of the injectables, such as interferon, figuring out enrolling on clinical trials.

So – and then, if a patient, young and fit, with myelofibrosis, you’ll want to be consulted with a stem cell transplant doctor. And then, finally, as if that wasn’t enough, I think a good pharmacist team is important nowadays to go over the drug-to-drug interactions, side effects. It’s not just about the JAK inhibitors but all the other medicines – antibiotics and everything else – that may be a bit unique to the MPN patient compared to the general cancer patient.

Katherine Banwell:    

Right. Lately, we’ve been hearing this term “shared decision-making,” which basically means the patients and clinicians collaborate to make healthcare decisions. And it can help patients to take a more active role in their care. So, I’d like to get your thoughts on how best to make this process work.

Dr. Pemmaraju:         

This is a passion area to me. I think this is so important that  you bring this out. I think a generation or two ago, Katherine, it may have been common for there to be more of a one-way monologue, if you will, doctor to patient, and that may have been the majority of the conversation before.

I don’t see it that way anymore, and most of my colleagues don’t either. I think it should be a dialogue, as you said. It should be a back-and-forth communication, one that learns and evolves over time as any real relationship would, right? Outside in the real world. So, I think that’s important. Number two, I think trust needs to be earned, not just given.

So, that means patient and physician, and really the physician team – so, all the other members of the team – building that trust over time through frequent communication, visits, all of this. And then, finally, I think the key here is that a lot of patients always ask, “Hey, what can I do on my own?” I’ll tell you what you can do. You can be involved and read and empower yourself if you’re able to, if you’re able to and you can. Many may not be able to due to their illness or for other reasons.

But if you are able to, I think it’s great to read online. There, I just said it. Let me repeat it to make sure everyone heard that. I want you to read. I think it’s fine. Consult Dr. Google. What’s the worst that happens? The worst that happens is you find misinformation. Well, don’t keep it to yourself. right? So, Google, look up things, go to social media, see what experts in your area are talking about, go to Facebook, go to the patient groups. But remember, everyone’s case is different. Someone else’s is different from yours, and yours is different from the next. So, gather information like a sponge.

Formulate it, synthesize it in the way that only you know how to do, bring some notes, and then talk about it with me at the next visit, “Hey, I saw this on the Internet.” “Okay, great, let’s talk about that.” Or, “Hey, this new formulation of interferon is coming.” “Great, let’s talk about it.” So, gather information, sort out signal from the noise with your healthcare team. Sort that out and then move on, move on, move on. So, I think these are some of the aspects of what’s called shared decision-making. No longer a monologue, one-way street. Let’s have a dialogue, let’s have a partnership, let’s figure out a way to empower each other in this journey.

Katherine Banwell:    

We’re going to talk in a few moments about online research and how well that works or how well it doesn’t. But let’s talk about treatment goals first for ET, PV, and MF. What are the goals of treatment from a clinical perspective?

Dr. Pemmaraju:         

Well, I think the goals are divided up into three factors. So, I think for the MPN patient, goal number one has to be what the patient themselves want to achieve.

Oftentimes, that’s different than what’s on the numbers with the labs and what the physician wants. So, I think a lot of our patients correctly are suffering from – or mentioning to us that they’re suffering from quality of life issues. So, fatigue is the most common manifestation of all the MPNs, followed by bone pain, night sweats, inability to concentrate, etcetera, etcetera.

So, I think quality of life is the goal of most people, and I think that’s an admirable goal. And some of the medicines can help that. Some can actually hurt that in the short term. So, let’s put that as bucket number one. What does the patient want to achieve? Usually, it’s the alleviation of fatigue, itching, bone pain, etcetera.

Number two, I think, is the sort of on-paper game, if you will, right? So, what do the labs show, what does the bone marrow biopsy show, what does the spleen show? I think all of that is good, too, in that bucket. And clearly, if someone has transfusion dependent anemia, two times a week needing blood transfusions, and whatever treatment you can do can alleviate that down to once a week, once a month never – okay, that’s a win for the patient.

And then I think, finally, our goals. You’re right. You asked me specifically “What are my goals for our patients?” Well, I want to see that your overall survival has improved if I can. So, your length of life, your quality of life has improved, minimization of side effects from whatever therapy we’re doing. If we’re going on a clinical trial or combining therapies in a novel way, that you’re not experiencing some brand new or idiosyncratic toxicity or side effect.

And then, finally, I think the key is to monitor for, let’s say, other things. Are you developing a second cancer, a second blood cancer? Are you having another problem that’s outside of your MPN, such as iron deficiency anemia or thyroid disease? Something that’s extremely common, has nothing to do with the MPN, but is also happening. And then do you have a healthcare team?

I failed to mention in your earlier question the primary care doctor, right? Let’s mention that person as well. If our patients have the general practitioner who they had already been seeing before the MPN diagnosis, or at least established one after, then some of these important aspects, like cancer screening, cholesterol checks, some of these other important things can be done in parallel to the MPN therapy and then, of course, combined at different points.

So, these are kind of my benchmarks for goals of therapy. They will vary from patient to patient and, of course, from case to case. The patient with advanced intermediate to high-risk myelofibrosis going to transplant, well, that’s markedly different from the patient who’s young with ET with no blood clots and relatively controlled blood counts. So, different goals there, Katherine.

Katherine Banwell:    

Right. Right. So, you just mentioned a couple of factors that you take into consideration, but there are others as well, I think. What about the patient’s age and overall health, for instance?

Dr. Pemmaraju:         

Could not be more important. You’re right. I think age – and let’s use that as a surrogate for what we call ECOG performance data. So, the overall kind of fitness of a patient, as you said, may be the most important factor. And then followed by these other conditions, so-called co-morbidities. I’d like to talk about that for a second because that’s a lot of the program here. Depending on a patient’s age, performance status, fitness, and other organs that are involved, that actually leads to a couple of important points.

One, it may limit or reduce the number of treatment options that a person has based on their ability to even tolerate it in the first place. Both oral chemos that are available, some of these clinical trials that need to use an IV drug.

Number two, it may predict how your overall survival is going to be. So, perhaps your MPN, as we used in the other example, you have an earlier stage MPN that really doesn’t require treatment. It requires active observation.

But then on the other hand, you have advanced heart disease or kidney disease. That may actually do you more harm in the end. So, that’s actually very important that you bring that up.

And then, finally, right, is this concept that you have the co-morbidities and then you have the MPN, and then they kind of change and morph over time where one is the dominant issue, the other isn’t. And so, you do need that decision care team as you were mentioning earlier. So, let’s definitely say that out loud that that matters. And I think it also reminds us that nothing is in a vacuum. The MPN doesn’t exist in an isolated space, right? So, your MPN co-exists with your heart disease, your kidney disease, your lung disease, your past, your present habits, anything.

Katherine Banwell:    

Exactly.

Dr. Pemmaraju:         

So, I’m really glad you brought that up. And I think also, to your point with the shared decision-making model, I think sometimes, as physicians, we may not ask, and as patients, we forget to mention, “Oh, X, Y, Z in my history,” or “Oh, I’m taking this herbal supplement.” Sometimes these things are important to mention.

So, when in doubt, bring up everything to your care team so that you can make decisions together.

Katherine Banwell:    

Right. It might help to make notes before you go in to talk to your doctor.

Dr. Pemmaraju:         

Sure. Sure, absolutely. That doesn’t hurt, and it could help you at least organize your own thoughts even if you don’t use them in the visit.

Katherine Banwell:    

Exactly. Yeah. Dr. Pemmaraju, let’s talk about biomarker testing. Can you help us understand what biomarkers are and how they may affect treatments?

Dr. Pemmaraju:         

Yes. Biomarkers – I think that word gets mentioned a lot with really no definition, because it’s one of those words that can be whatever someone wants it to be. So, you’re right. For us, it’s a very important word in MPN. Bio meaning of life, scientific, and then marker meaning some kind of a measuring stick that has a value.

Well, there are two ways to look at biomarkers. One is the obvious, which is we have the defined big three molecular mutations. So, that’s JAK2V617F, followed by CALR mutation, followed by MPL. Those are the big three. Those make up about 90 percent of all patients with MPNs. You’re technically not born with them, although new data suggests that you may acquire these mutations right after birth. So, those markers are important, because they can be used to diagnose the disease, right? Particularly in the challenging patient. They have high platelets, you can’t tell if it’s reactive or ET. Okay, so they’re helpful with diagnosis.

Maybe some studies have shown that some of these markers can be predictive, Katherine, of blood clots. Let that research be ongoing. And then, obviously, some of these may be helpful in terms of designing the future treatments, particularly targeted therapies. So, I think biomarkers are part of our field, if you look at it that way, at diagnosis and risk stratification prognosis. But there are other factors that are starting to come out. One is there are molecular mutations outside of these big three.

So, outside of JAK2, CALR, and MPL, that are very important actually. Not everyone is checking for them. They are ASXL1 mutations, EZH2, IDH1 and 2, so on and so forth.

So, these are extended molecular markers that can be checked at some doctors’ offices that now, in the latest scoring systems, if you have one of those or more than one or two, they can elevate your risk score. So, if you have low-risk or intermediate-risk myelofibrosis, they may make you intermediate or high risk.

So, that may be a bit more complicated than what most people are aware of. But just so you know, there are markers that can be readily checked that can tell if your disease may be a bit higher risk than we though, say, 10 years ago.

I think other biomarkers that we look at are some of the labs that are just the regular labs that are on almost every panel, but they can tell a lot about the disease. There’s the LDH, lactate dehydrogenase. There are several markers, such as CRP and sed rate.

So, anyway, there are a lot of labs that we can check depending on where you are in your disease state that can kind of tell us a lot about how inflamed you are, how active your disease is at the moment, and then that will lead to further confirmatory tests. So, I think, yeah, in general, this is an active, developing area of research in our MPN field.

Katherine Banwell:    

It seems like results could really influence therapy choices then. So, do you think patients should ask for these tests specifically?

Dr. Pemmaraju:         

I’m a big fan of patients being empowered to ask anything that comes to mind. And again, that’s why I love this discussion because maybe there might be some people out there who are shocked, frankly, at what we’re talking about here. I think it’s great to do what you said. Yes. I think do your research, online or otherwise. Come up with a list of questions. Bring – if you’re able to, of course – if you have the ability to, bring one person with you. Or nowadays, on the telehealth, we put one person on through the phone during the pandemic time.

And then – yeah. I mean, yeah, sure, just you hear about something, ask about it. The worst thing that your doctor says is, “Hey, that’s only a research test. That’s not available.” It doesn’t hurt to ask. And it may help to lead to other discussions. I think it’s also a good idea to get a second or a third opinion if you need to. There, I said it. It’s your body, it’s your life, it’s your choice. I think, yes, advocate for yourself, because at the end of the day, who else is going to do that?

Katherine Banwell:    

Absolutely. Dr. Pemmaraju, are there other questions that patients should consider asking about their proposed treatment plan?

Dr. Pemmaraju:         

You know, I think the biggest thing that I think is getting left out in the rare blood cancers that I spend all my time in is the ability and access to clinical trials. And that’s one thing I wanted to discuss with you this morning, which is you’re seen in your local doctor’s office. They’re doing the heroic work, and I really think it is, of seeing breast cancer patients, prostate, lung, colon, PV.

It’s just the difference between the frequent, common tumors that get chapters dedicated to them in the board review testing and whole months dedicated in the oncology fellowship compared to the patient with the rare blood cancer that, really, you may only encounter once or twice in your career. As compared to, say, me, where I’m a specialist in only that area.

I think that we – look, here’s the deal. Even today, only 5 to 7 percent of all oncology patients are ever referred to – are ever enrolled on a clinical trial. Clinical trials oftentimes are seen as last resort, last ditch. And I understand that. In fact, I even thought that before I went into medical school.

Then once you get to this point where I am, you realize, wait a second, clinical trial, oftentimes, are frontline programs. Yes, sometimes they’re randomized, sometimes they’re not. Very few times does anyone get placebo, right? Which is what a lot of people are worried about. Or if they do, it’s two drugs versus one plus placebo. Anyway, so there are a lot of different things that are clinical trials.

But we realize now that oncology has so little known information still in 2021 and beyond. So the ability to enroll in a clinical trial, be referred to it, travel to it, know about it, get on it, you’re contributing so much information to not only yourself and patients in your cohort but possibly for the future. So, that’s my only plug, is I wish that we would all ask each other more about “What clinical trials are available, how do I look them up, do you recommend this for me, or can I figure out with you how to travel and do all that stuff?”

So, I think clinical trials in rare blood cancers such as MPNs are underutilized, under-referred to, under-thought of. And then even when we are able to get people there, Katherine, it’s difficult to keep people traveling, particularly vulnerable people.

Katherine Banwell:      

Yeah. We have a question from a newly diagnosed PD patient. Sharon says, “I’m just about to begin Jakafi. What can I expect?”

Dr. Pemmaraju:         

Yeah, great question, right? So, with ruxolitinib or Jakafi, I think the biggest couple of points here is, for what’s known, this is the first-in-class JAK inhibitor that we have the most experience with.

So, now we have over a decade-plus of experience. I guess general things are general, right? This is not specific medical advice. That’s not the intention of this program. But, in general, I would stick with what’s on the package label insert, and there are a couple things we know.

One is this is a highly effective drug. This drug, which we have tested now in multiple, multiple, multiple different trials in myelofibrosis, polycythemia vera, now approved in a form of graft-versus-host disease, different doses. So, I would say check the dose for your particular disease and indication. Double-check it with your pharmacist. Make sure there are no drug-to-drug interactions.

Number two, I think what’s important is that some patients on this drug can experience immunosuppression. So, that means that you may be at risk for some infections, and there’s some nice literature about that.

So, check with your doctor about that, particularly reactivation of old infections, looking out for viral infections, such as herpes zoster or shingles. And then I think the other key here is to watch out for the modulation of your disease. So, a lot of folks have big spleens, Katherine. Those shrink down. Then patients get their appetite back, they’re able to eat, and so some people can have weight gain that then goes the other way. So, these are some of the things you want to watch out for.

But, in general, read the package insert. If you have the ability to, it’s worth reading the – if you can, read the paper, right? Go read the New England Journal paper or – if you can look at that. And then make sure you talk to your local pharmacist and ask the same question there. You might be surprised at some tidbits and pearls you can pick up.

Katherine Banwell:    

Right. Once on therapy, how is the disease monitored, and how do you know if the treatment is working?

Dr. Pemmaraju:         

Yeah. So, it differs from each disease, but let’s take polycythemia vera for a good example. So, let’s suppose you have polycythemia vera. I think there are three markers here that you can check. One is the blood counts, right?

So, you want to make sure that the blood counts are controlled. New England Journal, five or six years ago now, our Italian colleagues published a very seminal paper which shows that the goal of therapy should be that the hematocrit should be below 45. So, that’s actually a very nice number to have. So, not just waiting for symptoms of the disease but keep the number low. And if you do that, that correlates with decreased cardiac events, thromboembolic events.

Number two, I think that, besides the blood count, the spleen. The spleen and liver size also is a nice surrogate for how the disease is doing. So, if that’s enlarging or getting out of control, that may be time to stop what you’re doing, reassess. The disease may be progressing to myelofibrosis, for example.

And then I think, lastly, the absence of stuff actually helps, too. So, the absence of major bleeding, the absence of blood clots, the absence of transformation to MF. I think if the quality of life is good, you’re decreasing blood clots and bleeding, you’re not going to a more advanced disease state, these are all wins for us with p. vera.

Katherine Banwell:    

You touched on this briefly, but I’m wondering when a patient should consider changing treatments.

Dr. Pemmaraju:         

Yeah, changing treatments is more art than science, I would say. So, it does – that’s one of those that is kind of specific from patient to patient. In general, what we just talked about gives you that guidance. So, in polycythemia vera, since we brought that up earlier, uncontrolled blood counts despite maximum medication intervention, the phlebotomy requirement being untoward and impossible to keep up with, the spleen size growing out of control, the quality of life being impossible – these are some aspects to look into changing therapy and/or clinical trial.

But remember, it’s not a one-size-fits-all, right? So, some patients, the counts – some of these things may or may not actually play out. So, it has to be more of a gestalt, more of a total picture there.

Katherine Banwell:    

Yeah. Why is it so important for patients to speak up when it comes to symptoms or treatment side effects?

Dr. Pemmaraju:         

Well, I’m going to be that magician who you watch the TV show, they give away all the secrets. So, this is the big secret. Your doctor cannot read your mind. I hate to say that, Katherine. I just said it here, and it’s going to surprise some people. No, I mean, seriously. Right. So, I think the problem with the MPNs – not the problem, the caveat, the difficulty – is if you are a patient, you have this war that’s suffering inside of you. I know that as an expert person. You know that as a patient. But whoever you’re sitting in front of is not going to know that.

And there are two reasons for that. One is you don’t look like that. Most of our patients – whatever this is, I’m going to put this in big air quotes, so in case someone’s not watching this and they’re only hearing, I’m putting air quotes. People say to my patients, “Wow, you don’t look like a cancer patient.” Whatever that means, right? So, most of our patients don’t have their hair falling out, etcetera, etcetera. So, there’s that aspect of it, the visual education part of it.

Then there’s also the part, which is a lot of these symptoms burdens are not obvious on the physical exam. You cannot tell by talking to someone or looking at them if they have night sweats, bone pain, even itching, any of these things. Fatigue. You can’t tell if someone has fatigue most of the time unless you ask them. So, this is one of those where shared partnership in decision-making is not just a generic phrase. This is important.

I would say that for a patient with an MPN, the MPN symptom burden – the questionnaire, the 10 questions that we now have settled on – that can tell so much more or as much as the physical exam or the blood counts.

So, it’s imperative. It’s not just a luxury. It’s imperative. And if the patient themselves is unable to speak up, then if the advocate or caregiver or loved one can, if that person is available.

The other point I would say to this is that oftentimes the symptoms can precede – they can come before laboratory changes, physical exam changes, all these things. So, a constant, constant communication, “Hey, I was playing 18 holes of golf last year.”

“Now I can’t even get out of bed.” Hello? That tells you more than almost anything you can read on a piece of paper. So, you, as always, are spot-on with what you said. And this is the case where people say, “What can I do to help my care?” This is it. Speak up, speak out. It’s your body, it’s your life, make sure you feel empowered to do that.

Katherine Banwell:    

Right. It’s important to have that dialogue. Dr. Pemmaraju, you’re very active on social media, and patients often share information with one another. So, what advice do you have for patients to ensure online sources are actually credible?

Dr. Pemmaraju:         

Wow, great question. First thing I would say is I encourage everyone to get out there, so that’s key opinion leaders, local physicians, nurses, pharmacists, patients, caregivers, everyone. But Part two is what you said is true. Most everything out there is noise. It could be garbage. It could be background. It could be misinformation. So, you do have to have some way to filter it.

I call it signal from the noise. That’s a common phrase that a lot of people on social media use. I guess three things that I would give as tips. One is don’t be afraid to read and get on there, but I would just say whatever you read, take it with a grain of salt, as you said, and just write everything down where you have it organized.

Number two, tend to gravitate towards known experts and known sources. So, for example, you mentioned that I’m on there. That’s great. Ruben Mesa, our great friend and colleague, etcetera, etcetera. So, if you know who the 10 or 15 thought leaders are on Twitter or social media, see what they’re saying directly. That’s nice, because it’s straight from them to the public.

And then three is stick with the organizations and entities that are trusted sources. New England Journal of Medicine, ASCO, ASH, programs such as yourself, etcetera, etcetera, who are trying to put out there the latest and honest information.

Okay. So, now the fourth part, though, I think is the most important, which is what we said earlier, which is whatever you look up, discuss it with your doctor and your physician team. Period. Because no matter what research you did, no matter what patients groups you join, there might be something that either doesn’t apply to you, or worse, as you said, it could be actual misinformation, and it’s a red herring.

So, maybe find information, figure out a way to filter it, cross-check it, and then bring it up to your doctor team. I think that’s a winning way for success with information nowadays.

Katherine Banwell:    

Yeah. That’s really helpful information. Well, we have another audience question. This one is from Richard. He wants to know, what advice do you have for caregivers, and how can he be supportive during appointments?

Dr. Pemmaraju:         

Yeah. Richard’s question really is so important. Really, before the pandemic and now with the pandemic this extended time, this is the most important question that’s coming up. This is a challenge. I think a lot of our patients who are older, frail, live alone, they don’t even have the option to do that. That may be 25 percent of our patients right there,

And that’s very heartbreaking and difficult, and clearly, their care – it may not be compromised, but it’s certainly limited in some ways without getting that other perspective, right? So, I think that’s important.

Now, out of the 75 percent of the people who may have someone that can be a part of their life, a lot of these folks, Katherine, are limited because of the pandemic. Most hospitals, smartly, I think, still have restrictions on not allowing every single person in the building just for health and safety protocols. So, telehealth has had to be a substitute, I would say, for that, and in a lot of cases, has been helpful. In some cases, frustrating, obviously, with technical difficulties, etcetera, etcetera.

I would say that the key is – and I really want this to be very specific. It would be easy to just say, “Yep, bring a loved one to your visit.” No, it’s not that easy, right? So, now, during the pandemic, I think two things are very important and what I’ve noticed. One is, if the patient is able to, if their health allows them to, prime the loved one or caregiver, “Hey, I’m going to be in the doctor’s office from this time.”

And I always say make it like the cable person visit, right? From 8:00 to 5:00. So, “Hey, today, on Tuesday, if you can have your cell phone on you, that would be nice, because I’m going to patch you in, and you can listen in the background.” This is actually a key pearl I can give to people. You’d be surprised how helpful that is. Because most people, if they’re not living in the same household or whatever – “Oh, I didn’t even know you were going to be,” – okay.

Number two, when the loved one or caregiver is involved, which I encourage for everyone, try to discuss with them the night before, if your health allows you to, to go over some of the key questions. Say, “Hey, guess what? I only understand about 7 to 10 percent of what goes on in these visits, but I need you to ask this.” So, you can kind of prime your loved one to do that.

And then, lastly, you had mentioned earlier to have this list of questions. Well, that’s a great thing to give to the caregiver, right? So, if you’re able to use email and your family member is in California and you’re in Texas, maybe a quick email the night before.

“Hey, here’s what I’m thinking. In case I forget, will you ask this to the doctor?” A lot of these visits may only be five or 10 minutes, but you’d be surprised, if you have a list of two or three questions – boom, boom, boom – and then it’ll alleviate those worries there.

Lastly, I would also say don’t feel – I want to tell this to the viewers out there. Don’t feel pressured when you’re in the visit with us that you have to get every single thing out. And what I mean by that is now with email and the electronic medical record portal systems, there is some ability to contact people during – I’m sorry, after and between visits. So, maybe that might help you to not feel so much pressure in the visit.

Katherine Banwell:    

Yeah. Very good advice. Thank you. Before we end the program, have there been any recent developments in MPN treatment and research that make you hopeful?

Dr. Pemmaraju:         

I have a lot of optimism and hope. It really blossomed over the last two years. I’m happy to report to our viewers – and this is incredible, I never would have predicted this. There are over 10, maybe 13, Phase 3 clinical trials that are in the clinic now or opening soon.

Phase 3 meaning sort of the latest – one of the latest stages of clinical trial development for new drugs. And a lot of these drugs are combinations. So, a lot of them, you’re on your ruxolitinib, for example, you’re on your JAK inhibitor, and then you add in the second agent. This is very exciting. I, myself, am leading or a part of several of these. I mean, we could have never envisioned this five years ago. So, not only these drugs have shown encouraging activity in the Phase 1 and 2 – so, the earlier stages – so, now we have to confirm and test them in larger trials. So, stay tuned for that, whether you can participate directly or at least follow along with the information.

And then the other piece of excitement is that there’s a lot of beyond JAK inhibitor drugs. So, that means novel pathways, new drugs that have nothing to do with JAK that can either stand alone by themselves or be combined. That’s another exciting area. We have multiple classes of drugs emerging from the lab into the clinic now that I hope will have a lot of benefit for our patients.

So, tons of optimism and excitement, frankly, that just wasn’t there five years ago.

Katherine Banwell:    

That’s wonderful. Dr. Pemmaraju, thank you so much for joining us today.

Dr. Pemmaraju:         

Thank you, Katherine. I just love the chance to spend time with you guys. I hope to do this soon one day.

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.

How Can I Tell if My CLL Treatment is Effective?

How Can I Tell if My CLL Treatment is Effective? from Patient Empowerment Network on Vimeo

How is chronic lymphocytic leukemia (CLL) treatment effectiveness monitored? Dr. Lindsey Roeker discusses the potential symptom improvements that can manifest and what she looks for during examinations with her patients.

Dr. Lyndsey Roeker is a hematologic oncologist at Memorial Sloan Kettering Cancer Center. Learn more about Dr. Roeker here.

Download Guide

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Transcript:

Katherine:                  

How do you monitor whether a treatment is working?

Dr. Roeker:                 

So, a lot of it has to do with the CBC, so your normal blood count, and what we’re looking for is improvement in hemoglobin and improvement or normalization of platelet count. And for many people, those, either anemia or low platelets, are the symptoms that drive people to be treated in the first place, so we’re looking for those parameters to get better.

With a lot of people with CLL, totally understandably, because it’s the number that’s the most abnormal, really focused on white blood cell count. 100 percent understandable.

I always tell people that that’s actually the part of the CBC that I care least about, and the reason is that, for patients on BTK inhibitors, we expect to see the white blood count actually get higher before it gets less high. That’s actually just a sign that the drug is working and it’s pulling CLL cells from the lymph nodes into the bloodstream. So, that’s actually a good sign that it’s working, and that lymphocyte count, at least in the beginning, isn’t a great marker of how well the drug is working.

The other thing that’s important is the physical exam, so looking for whether any lymph nodes that were enlarged have normalized or gone away, and also feeling the sides of the spleen, because the spleen can become enlarged with CLL, and it’s important to make sure that’s normalizing, as well.

And then the last piece is talking to people, so making sure that if they were having fatigue, or fevers, or night sweats before they started treatment, to make sure that those symptoms have gone away. And that’s kind of the three things that I use. I use the blood counts, the physical exam, and the interview with a patient to really understand how their disease is responding.

Have You Had These Essential Myelofibrosis Tests?

Have You Had These Essential Myelofibrosis Tests? from Patient Empowerment Network on Vimeo.

What are the essential tests that should follow a myelofibrosis diagnosis? Dr. Joseph Scandura reviews the necessary laboratory testing, along with a discussion of next generation sequencing, and explains how often bone marrow biopsies should take place.

Dr. Joseph Scandura is Associate Professor of Medicine and Scientific Director of the Silver MPN Center at Weill Cornell Medicine. Learn more about Dr. Scandura, here.

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Transcript

Katherine Banwell: 

What testing should take place following a myelofibrosis diagnosis? 

Dr. Scandura:  

So, a diagnosis of myelofibrosis always comes after a bone marrow exam and a physical examination. Often, patients have an enlarged spleen and blood count testing and a variety of other laboratory tests. So, after that and a diagnosis is made of myelofibrosis and, sort of, coincident with the diagnosis, we often look for molecular markers of myelofibrosis. So, these are malignancies of the bone marrow, cancers, if you will, on the bone marrow, although the term is scarier than or is different than what we think of for many malignancies in how it acts. But the myelofibrosis, this is a disease that’s characterized by, really, mutations in the malignant cells, the abnormal cells. 

They’re really just one of three genes. And so, JAK2 being one of the genes, calreticulin or CALR being another one, and MPL one.  

And more than 90 percent are people having mutation in just one of those three genes. And so, often at the time of diagnosis, tests for those mutations are done, and they help eliminate the possibilities of other causes of myelofibrosis – infections, rheumatological diseases. Sometimes, you can have marrow fibrosis but they don’t go along with mutations and the same clinical situation. And so, at the time of diagnosis, we usually know something about a mutation in JAK2, CALR, or MPL.    

More commonly now, and it’s increasingly common over the past 10 years in, I would say, in New York City and many places across the country, we also look more broadly for other common mutations in the MPN cells. And these are what we refer in the batch as next generation sequencing or NGS panels, and we use the term panels because we’re looking at from a few tens to even 100 or a couple hundred genes for mutations that occur far less frequently than in JAK2 or MPL or CALR.  

But they occur often enough that some of them we use to help guide treatment decision-making or approach to therapy. The reality of it is that that the technology to sequence and identify mutations has really outstripped our knowledge of what to do with all of that information. 

And, for the vast majority of people, it comes down to do you have a marker, a genetic marker that tends to go along with higher risk, meaning a higher likelihood of something that we don’t want to have happen. And in that instance, although it may be looking at a hundred or so genes, it comes down to a binary thing – either you have or you don’t have. 

Katherine Banwell:

Is there any other testing that you usually want to do? 

Dr. Scandura:

Laboratory testing, for sure and, as I mentioned before, a bone marrow exam. But physical examination, some people might do imaging of the spleen size. Honestly, I don’t routinely do that outside of the setting of the clinical trial. I don’t really think it dictates therapy very often. 

And if the spleen is so small that you can’t feel it on physical exam, it probably isn’t clinically meaningful anyway in terms of something to treat. It might be there, but it doesn’t really change things too much.   

Katherine Banwell:

How often should patients have a bone marrow biopsy? 

Dr. Scandura:

So, I’ll answer there is no standard in terms of monitoring for myelofibrosis with the marrow or otherwise. My personal approach is I do a marrow when I think it’s going to help medical decision-making. And so, for a patient who’s got early myelofibrosis, who’s been very stable, responding well to therapy, that could be three, five years between marrow exams. 

For somebody who’s being considered for a clinical trial, oftentimes, a marrow exam is required before they start on the clinical trial and at various intervals afterwards. If there’s somebody who had been stable and something is changing, like the blood counts are changing or his symptoms are changing, or any of a number of clinical features, then I might look in the marrow to see what’s happening there, to see if explains and can help guide a treatment approach to help people feel better. So, there is no single standard, but my personal approach is to do a bone marrow exam when I think it’s going to help make a decision.  

Shared Decision-Making: The Patient’s Role in Treatment Choices

Shared-Decision Making: The Patient’s Role in Treatment Choices from Patient Empowerment Network on Vimeo.

What is the role of the patient when it comes to treatment choices? Dr. Brady Stein details how he partners with patients in decision-making for their MPN care. 

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.


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Transcript:

Katherine:                  

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 want to hear. I want to 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 are 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 going to 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 want to 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.

Self-Advocacy: Advice for Being a Pro-Active MPN Patient

Self-Advocacy: Advice for Being a Pro-Active MPN Patient from Patient Empowerment Network on Vimeo.

How can myeloproliferative neoplasm (MPN) patients be more pro-active in their care? Dr. Brady Stein shares advice to help patients educate themselves about the disease, while finding the right balance of knowledge to prevent them from feeling overwhelmed. 

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.


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Transcript:

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 got to 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.

Is My MPN Treatment Working?

Is My MPN Treatment Working? from Patient Empowerment Network on Vimeo.

During myeloproliferative neoplasm (MPN) treatment, specific blood tests and diagnostic measurements help to gauge a patient’s treatment response. Dr. Brady Stein details the criteria he assesses in monitoring the efficacy of a therapy, including patient-reported outcomes.  

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.


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Transcript:

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.

MPN Treatment Choices: Where Do Clinical Trials Fit In?

MPN Treatment Choices: Where Do Clinical Trials Fit In? from Patient Empowerment Network on Vimeo.

When considering MPN treatment approaches, clinical trials are a viable option for care. Dr. Brady Stein discusses clinical trials and factors to keep in mind when considering participation.

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.


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Transcript:

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 (Jakafi) 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 are often more visits, and there are 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 are a number of different clinical trial options, especially in myelofibrosis. I think that’s the disease area where there are the most clinical trials.

Understanding High-Risk vs Low-Risk Disease in ET, PV & MF

Understanding High-Risk vs Low-Risk Disease in PV, ET & MF from Patient Empowerment Network on Vimeo.

When looking at polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), how is risk determined? Dr. Brady Stein explains factors he examines when assessing risk to provide ideal care for each patient. 

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.


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Transcript:

Dr. Stein:                  

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.

What Are Treatment Options for Essential Thrombocythemia (ET) & Polycythemia Vera (PV)?

What Are Treatment Options for Essential Thrombocythemia (ET) & Polycythemia Vera (PV)? from Patient Empowerment Network on Vimeo.

When considering treatment options for essential thrombocythemia (ET) and polycythemia vera (PV), where do experts begin? Dr. Brady Stein details treatment considerations and how he determines the best approaches for ET and PV patients. 

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.


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Transcript:

Katherine:                  

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 are 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 are 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 percent 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.

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. Learn more about Dr. Stein, here.


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.

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.

See More From The Pro-Active MPN Patient Toolkit


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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.

See More From The Pro-Active MPN Patient Toolkit


Related Resources

 

An Expert Shares Key Steps to Take Following an MPN Diagnosis

 

MPN Treatment: Why Testing for Mutations Matters

 

What You Should Know About Progression in MPNs


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.