 So, as I like to explain in my patients, MPNS are not rare but they're not common, you know, so they comprise about 300 thousand to 350 thousand  individuals affected with these diseases across the United States, between myelofibrosis roughly about 20 plus thousand; and about a hundred and fifty thousand or so patients with essential thrombocythemia; and 150,000 or so with polycythemia vera. There certainly are some diseases that are much more rare, but clearly there are diseases that are much more common.

How do you think the rarity of these diseases affects awareness around the disease?

 Without question it still is a group of diseases that largely are not on the public consciousness. It is challenging have a disease that is not being talked about on “Good Morning America” or “The View” or other kind of widely held platforms. Most patients when they're diagnosed, it's really the first time they've heard about these diseases. And more importantly, their support structure, their friends, their family, their employers aren't very familiar with them and that frequently puts a patient in a bit of a tough spot having to both share that they have this diagnosis but also kind of explain what it is, how severe it is, etc.

 Does this also highlight the fact that there's a need for more research in this disease state?

 I think without question. This is a group of diseases that is linked with other diseases that in aggregate really does make it a much more common group of problems. So the MPNs are a type of a chronic leukemia, so they're relatives of other diseases like myelodysplastic syndrome, chronic myeloid leukemia, acute myeloid leukemia — and in aggregate these are diseases that are not uncommon and they're particularly common as we get older. So, as our population is greying, the prevalence of these diseases is increasing.

So the understanding of why people develop these diseases, why they're linked with aging, how we screen for them, how we prevent them, how we treat them is incredibly important. Advances in research in MPN patients might help many other patients with other types of blood diseases and vice versa.

In simple terms, can you discuss the different types of MPNS and how they're different from one another?

 So, first there's essential thrombocythemia. These are diseases, in particular, where patients have an elevation in their platelet count. They can have an elevation in the white blood cell count, but the elevation in the platelet count is really the hallmark of the disease. We believe the disease itself really originates in the early cells from the bone marrow.

Second is the disease of polycythemia vera. This is really characterized by an increase in the number of red blood cells, but there can also be an increase in the number of platelets or white blood cells and similarly a stem cell disease of the bone marrow.

Finally, there is the disease of myelofibrosis. Now this tends to be a more advanced disease in individuals that had progressed from previously having essential thrombocythemia, or what we call ET, or polycythemia vera, what we call PV. So, people can progress from one of those into myelofibrosis or people might have myelofibrosis as really the initial diagnosis that they have. Patients with myelofibrosis tend to have an enlarged spleen, they have significant scarring in the bone marrow, they actually can tend to have low blood counts.

 What are some signs and symptoms that individuals should be aware of that could be a result of an MPN?

 First, individuals can have changes in their blood counts. With ET, that can be to higher platelets or white cells. With PV, any of the cells can be increased. With myelofibrosis, some are increased or decreased.

Second, individuals can have enlargement of the spleen, an organ that's a filter for the blood under the ribcage on the left side.

Third, all of these diseases somewhat do predispose patients to developing a blood clot or bleeding and sometimes that's how we find the disease: An individual has an unexpected blood clot in the legs or lungs or other area or unexpected bleeding, they have blood counts taken and they see this abnormality.

And finally, patients can have various symptoms from the enlarged spleen, discomfort, filling up early when they eat, inadvertent weight loss, night sweats, fevers, and most importantly, fatigue across all of those diseases. Even itching can be a significant difficulty.

 If somebody's experiencing any of those signs or symptoms what do you think their first step should be?

 Their first step certainly should be to visit with their primary care doctor. These might be a sign of having an MPN, but of course, it might be a sign of other things. With any one of those symptoms that I've described, there's multiple potential causes but an MPN is an important thing for us to be mindful of. So, for example, although we watch for enlargement of the spleen in patients with MPNs, actually probably the most common reason for enlargement of the spleen in the country would be someone with an infection or someone with mononucleosis. So, every one of these is a possibility. But there is no one symptom that says, “Aha, this is automatically an MPN.”

 To bring it all together with the basics of the disease, what would you say is the most important thing for a patient who's diagnosed with an MPN to know about?

 I think the most important thing is for them to really understand their disease and have that conversation with their doctor. There's a lot of great information out there from 

 magazine, from the Leukemia Lymphoma Society, from the MPN Education Foundation, from the MPN Research Foundation. There's a lot of very high-quality educational materials out there. Which of those materials are very specific and accurate for that individual patient? That really needs to be kind of aligned with their doctor.

I have seen patients that have read very good, high quality materials, but materials that really were not directly relevant for their stage or type of disease. So I think kind of a curated education around your disease is very important. These are chronic diseases. So understanding them, understanding what we watch for, if you're on therapy, understanding why you're on therapy, what do we watch for, why that therapy is very important. Care of an important partnership between the patient and their physician.

Understanding the Basics of Myeloproliferative Neoplasms

After receiving a diagnosis, what is the best way for patients to learn more about their disease?

 Fortunately, there are some very high-quality materials out there. First they should really learn from their doctor and have their doctor. (They should) certainly describe in their own words what they feel, the disease they have, what are the implications, what are the implications in terms of therapy. Frequently, it's a lot of new information for patients. So, I certainly welcome patients in my practice to take out their smartphone and tape the discussion so that they can both hear it but they can also share it with loved ones if they were not in the room or things of that nature. There are some high-quality educational materials both from our education foundation, the MPN Research Foundation, the Leukemia and Lymphoma Society, amongst others.

Now, as with all good patient education, it's important that you're reading the right material that is specific for your disease. There is more than one type of MPN and even within the MPNs, there is a wide range in terms of how individuals are affected. So, it is important that they do reading, but reading that is guided or selected by their physician or health care provider to be sure that they're reading accurately regarding their disease. Similarly, if they're on medications there is typically educational materials regarding those medicines that their health care provider may be able to point them to so that they can best learn about which therapy they are on.

Why is it important for a person's loved ones or their caregivers to also learn more about this disease type?

With diseases like this, it’s a chronic disease. So, for most individuals we expect this is a disease they are going to live with for the rest of their lives. So individuals that are important in that individual's life, it's good that they understand what they're facing both in terms of their needs to be accommodations. There are some times that patients have accommodations at work, if they have difficulties with fatigue and have a hard time working a traditional schedule or other sorts of physical activities or things of that nature. Surely in terms of their loved ones or in terms of understanding what they're going through and supporting them.

Not infrequently, MPN patients can have symptoms but that are not overtly obvious. I mean patients might suffer from significant fatigue that is from the disease. It can be limiting, but they don't look any different. So, as we try to support those individuals as a caregiver or loved one it's important for us to know that to be able to help and support them.

After receiving a diagnosis, why is it key for a patient to seek a specialist that treats myeloproliferative neoplasms specifically?

 The myeloproliferative neoplasms are relatively uncommon diseases. Many community hematologists and medical oncologists may have less experience with them. I will not say that that's universally the case in that I certainly have found community hematologists that treat MPNs very well and have a reasonable number of patients and that experience. But for those that do not have that experience, or this is their first, or they just have a couple MPN patients, as a chronic illness it frequently is helpful for many patients to also have seen an MPN specialist, of which many of the large cancer centers have someone that focuses on these now so that they can be a helpful part of the treatment team in terms of assessing risk discussions regarding therapy options, potential opportunities of clinical trials, or in those most advanced cases, the inclusion of other specialists who focus on the therapy of bone marrow transplant that tends to be more specific for individuals that have higher risk myelofibrosis. But again, as you can get a sense with MPN patients, sometimes the really need an entire health care team not just one individual helping care for them.

Can you just explain how a multidisciplinary approach comes into play when it comes to MPN care?

 Well, with MPN patients, first they have their main provider, which is typically a hematologist that is certainly helping guide therapy, adjust medications, prescribe medications, things of that nature. Without question, that individual has their own team that are key parts of that care. That can include a nurse, that might include a nurse practitioner or an MA that are helping track symptoms, track medications, toxicities, interval symptoms or other issues which arise.

Clearly these individuals will have a primary care physicians. How this relates to the rest of their health care is important. That is another key part of that team. So, if I have a patient, from a distance they need phlebotomy, they need other things, I'm interacting with their primary care physician. If they have other medical problems, I may be interacting with their ophthalmologist asking if it is okay for them to have their cataract surgery or their knee replacement or their orthopedist or if they have a heart attack, was it from the MPN, was it independent of the MPN, interacting with a cardiologist. So again, their broader health care team but as a as a core part it at least includes a primary care doctor, a hematologist, nurses, MAs, NPS, etc.

 How can patients become better informed so that we can improve patient-physician conversations?

 I think really following some of those great materials from some of those sources — Leukemia Lymphoma Society, ours and others –            are really key. I think understanding a bit about what is the disease, some of the evolving understanding we have regarding genes such as JAK2 and what role they play, what we are monitoring if a patient is on therapy, what to expect with that therapy, why are they on the therapy, what are the expectations and what to watch out for in terms of progression.

Usually if there is a change or a problem it doesn't conveniently occur at the time of a pre-scheduled visit with your health care provider, it occurs at some other time so having that partnership where they again can recognize that there's a difficulty and be able to alert their team is really key.

 Are there certain questions or things that patients and caregivers should be mentioning so that maybe we can streamline that conversation between patients and their physicians?

I think, one, they really need to be able to relay to their physician what sort of symptoms or difficulties the disease is giving them and what really has changed — how is it affecting them. Now, some patients are more reluctant than others about bringing these things up. They don't want to feel like they're complaining or things of that nature. Again, this is not complaining. You are sharing that with a crucial relationship with your health care providers so that they can help you.

Sometimes how you're feeling might impact our choice of therapy or adjusting the dose in therapy. Additionally, sharing with your physician any side effects that you might be having from your treatments is very important. There are treatments that might give you sores in your mouth that can make you uncomfortable, make it difficult to eat. Clearly, you would want to share that with your physician. We most certainly would not want to raise the dose of a medication if it was giving you mouth sores. In fact, we might choose to change it to a different medicine that you might feel better on. The goals of our treatments are to make the disease as invisible in your life as possible. In the ideal world, we could cure the disease. Research is ongoing to try to find a cure, but until we do, if we're able to make the disease as invisible in your life as possible that is a very good goal.

 As a health care provider, what would you say is your biggest piece of advice for a newly diagnosed patient with an MPN?

My biggest piece of advice is to learn a lot about your disease and also to make notes for yourself both in terms of what you have, what they expect, what questions you have so that you can relay those to your health care provider and really help to overcome that gap in knowledge and understanding. I find that there can be tremendous distress for individuals because of their lack of familiarity with such a disease. For many individuals, when they are diagnosed with this, it's the first time they've heard about it and they have never known anyone else that has had the disease. So they don't have a good frame of reference. That creates a tremendous amount of uncertainty and distress. The more we can alleviate that, the more individuals are able to come to at least a comfortable understanding of their disease and work to try to move past that.

Understanding a Myeloproliferative Neoplasm Diagnosis

 What are the current standards of care for treating the various myeloproliferative neoplasms?

 So it is very disease-specific. First, with essential thrombocythemia, pretty much all patients we consider a low dose aspirin except perhaps with some exceptions to try to decrease the risks of blood clots for these individuals. And then if individuals need medicines to control their counts and normalize those counts, particularly the high platelet count, we consider the oral medication of hydroxyurea which is a pill to try to control those counts. We might consider injections with pegylated interferon to help to normalize those. And then we might consider a plated lowering medicine called (Agrylin [anagrelide]) that helps to lower those. So for the ET, all of those medicines that are broadly used and available. There are some others but those are the main ones that are helping to decrease and normalize the platelets, decrease that risk of blood clots or bleeding in addition to the aspirin.

Now, for patients with polycythemia vera, it's similar but with a couple important nuances. First, most patients get aspirin to try to decrease the risk of blood clots or bleeding, but very importantly, in addition, in polycythemia vera, the red blood cell count is elevated and because of that we try to control that so that the hematocrit is less than 45%. The hematocrit is the percent of blood by volume that are red blood cells. So we should to have that be less than 45%. Now, like patients with ET, we then have medicines that we'll use to control the counts in some individuals: higher risk, not doing well with phlebotomy alone, difficult symptoms, a range of different reasons. We might still use hydroxyurea or interferon as we discussed similar like patients with ET, but importantly we have an additional option: a second-line therapy which is (Jakafi [ruxolitinib]) or a JAK inhibitor. And that can help to lower the counts but also improve enlargement of the spleen and symptoms. So ruxolitinib is most commonly for individuals that have more difficult polycythemia vera.

Finally, we have patients with myelofibrosis. This is the most difficult of the three MPNs. Our initial decision is whether we do something quite dramatic like a bone marrow transplant, which can potentially cure the disease; however, it's a very involved therapy and for that we use it in very specific sort of scenarios: younger patients, difficult disease, etc. For the majority of patients, we start as our first treatment with a JAK inhibitor, which now includes ruxolitinib but also recently approved (Inrebic [fedratinib]) — both JAK inhibitors that improve the screen, improve the symptoms, potentially help to prolong life, may have an impact in helping to delay disease progression. The patients started with the JAK inhibitor ruxolitinib first, if they don't have an adequate response, we may then consider going to fedtartinib or vice versa. So those are the main treatments and I'm sure we'll discuss in a moment some of the treatments that might be coming in the future.

 Are there any particular common side-effects that patients should be aware of from any of these treatments?

 Although aspirin sounds very benign, there can be risk of bleeding, nosebleeds and others, and your health care provider should be made aware. Individuals with phlebotomy, it's like giving blood but it can cause soreness in the arm and it causes iron deficiency which can lead to fatigue or other difficulties, again things to monitor for your doctor. Hydroxyurea might cause risk of skin cancers, mouth sores and leg ulcers, the things for us to be mindful of. Interferon sometimes can cause a drop in the counts, cause mood changes such as depression or hypothyroidism. Anagrelide can cause palpitations, diarrhea or an upset stomach. Ruxolitinib can drop the blood counts as the others can, and has a rare risk of infections like shingles or others, headaches, things of that nature and might slightly increase the risk of skin cancers. Fedratinib, we monitor for thiamine deficiency. a type of vitamin that if it's deficient in individuals it might cause confusion or some changes of that nature. It can drop the blood counts, it can cause anemia like the ruxolitinib dropping the platelets, and it really can cause some GI side effects. This sounds like a huge list of things, but again for the majority of individuals they don't have these things when they take these medicines but these are things that we watch for and again something that your doctor both should describe for you but things to be mindful if you start any of these particular medications.

Can you discuss some of the exciting trials that are going on and maybe any that you might be involved in at the moment?

 There are many exciting things going on and we'll take it disease by disease. So, first with essential thrombocythemia, there's both trials that are looking at very long-acting interferons, one called pegylated interferon versus anagrelide as second-line therapy for patients with ET. We're excited about that study. Interferons are being used, but have not been FDA approved yet for ET, so we’re excited about that part.

Additionally, we have a trial at my center and there's a national study going on with a drug from a company called Imago Pharmaceuticals that works against the cells in the bone marrow, the megakaryocytes, that we’re excited about.

For polycythemia vera, there are some drugs trying to help individuals by acting like hepcidin, which is a molecule in the blood, but to act like a phlebotomy. There's a drug from a company called Protagonist that is ongoing with that. There's other experimental drugs both with pegylated interferon that's trying to become approved in the US as it is in Europe. And there's other agents that are being tested such as MDM2 inhibitors that work against some of the biology of the disease.

Probably the greatest number of trials are in myelofibrosis. There truly are dozens and currently won't list those all. That's in part because these are our sickest patients so the need is the greatest and the hope is that again as we find things being effective in myelofibrosis we may then be able to advance them in to help patients with ET or polycythemia vera.

First, there's other JAK2 inhibitors which I’m involved with both studies trying to get both momelotinib approved, which can help both the anemia as well as spleen and symptoms and that's in an ongoing study for individuals that have anemia and have failed ruxolitinib. Similarly, there is pacritinib that is for patients with low platelets in myelofibrosis but can also improve screen and symptoms.

Then there are combinations with ruxolitinib with agents such as thalidomide to help improve anemia with navitoclax from AbbVie as a combination to be effective. There's combinations with the BET inhibitor from Constellation Pharmaceuticals that has shown very interesting activity both as front-line and combination or subsequently. CPI-0610 might have a deeper set of responses for spleen symptoms improving scarring in the bone marrow, anemia and things of that nature.

There are trials for people that are off ruxolitinib altogether. We have one from Avid200, an agent from Forbius, through the MPN Research Consortium, of which I'm an investigator. As well as that drug I had mentioned from Imago, 7289, that is being looked at for individuals with myelofibrosis. So, that's just even just a partial list but many things either as second line-for people that have failed ruxolitinib or adding on to JAK inhibitors for individuals that have had an inadequate response.

There is even cadence to try to help further improve the anemia drug called luspatercept that just got approved in myelodysplastic syndrome and hemoglobinopathies might be helpful alone or in combination for myelofibrosis.

 Why is it important and why should patients be getting involved in clinical trials?

Clinical trials are how we make advances. Clinical trials are how we improve therapy. To try to demystify clinical trials, what clinical trials are is just a very structured way of treating individuals and us learning whether the treatment is better or not. Currently they're hearing a lot about clinical trials because of the cOVID pandemic, whether there's trials to see is a vaccine effective or not, is it safe or not, is a therapy for someone who has a common infection effective or not, whether that's hydroxychloroquine or Remdesivir. We only learn about these things and answer these things because of clinical trials.

In MPNS, the situation is exactly the same. The therapies that we have, hydroxyurea, anagrelide, pegylated interferon, ruxolitinib, fedratinib, we only have them because we had clinical trials and people received those on clinical trials before they got approved. The key of the clinical trials is realizing it's a structured way for us to treat you as a therapy, see if it's effective, see if you're having side effects.

What it is not is a permanent obligation, meaning the patient is always in control. If you're on a clinical trial, if you take one tablet and you don't want to be on the clinical trial again you could say “I don't want to take it anymore.” If you sign the consent form and decide you don't want to take the medicine even before you've taken a single tablet, fine. It’s not it's not a contract. It is a structured way for you to try a therapy.

Many times it's the only way to be able to try a therapy before it is approved and that's because if we know for certain that the therapy is safe and effective and everyone should get it, then it should be approved. Before then, we're hopeful that it's helpful and the people that are on the trial might indeed be better off because they were able to receive that therapy. But that's the only way to receive that therapy, if for nothing else because the FDA wants to be sure that people are being closely monitored for side effects. So everything having to do with the clinical trials is really done under the principles of being sure that people will participate with them or are fully informed and are kept as safe as possible

 What would you say is the best way for patients to learn more about clinical trials and if they're eligible for one?

Patients can learn about potential clinical trials through clinicaltrials.gov, that is the main website run by the National Institutes of Health, but it really helps to share all the information regarding the trials that are out there. Whether a trial is appropriate for their situation and whether they're eligible is clearly a discussion between them and their health care provider. Clinical trials do tend to be very specific in terms of which patients, but also very much which specific phase of disease or features of the disease are key for the individuals on this study for us to be able to learn from that trial. So sometimes there is a trial available for a patient in a specific situation, sometimes there is not and that's okay. Sometimes being eligible for a trial is because your disease is being a bigger problem. If everything is perfectly stable and they're doing very well maybe there is a trial in terms of a survey study or donating blood so that research can be done. But a trial in terms of a new treatment is usually in the setting of there being an unmet need, meaning the disease is not being controlled as well as we would like.

 what would you say patients with this disease have the most to look forward to?

 Well, I think they have a tremendous amount to look forward to. We've made tremendous progress. There is unbelievable teamwork going on around the world now to better understand why people develop these diseases, why they progress and how to better treat them, as well as how to improve their symptoms, their quality of life and avoid progression. So, a lot to look forward to.

The research impacts patients in that it is not only done in MPN patients. We may learn advances in therapy are being used in other diseases of the blood or other cancers that may indeed have an important impact for them. And likewise, things we learn in MPN patients may help others. At the current time, one or more of the MPN drugs, ruxolitinib as an example, do have an impact on the COVID infection. In fact, ruxolitinib helps to decrease the inflammation in the pneumonia that COVID patients develop and was able to get people to come off the ventilators earlier. So again, an example of a drug approved for myelofibrosis helping a much broader group of people for different reasons. So that is really a two-way street: MPN advances help others but advances in other diseases clearly have the potential to help MPN patients.

Treatment Advances Aid Patients With MPNs, Others

 Can you discuss how MPNs have become more of a chronic disease now and what that means for patients?

 Really in fact, MPNs always were a chronic disease. In a bygone era, toxic drugs were commonly given which often themselves caused acute leukemia and end-of-life. Thankfully, those days are gone, and the newly diagnosed patients should not get scared when reading about information from those ancient eras. Now we have better advice based on more robust statistics, which prove what patients and long-established online support groups can easily see, that patients’ lifespan and productive years are often measured in decades — in fact, often many decades, especially for those diagnosed before or during middle age.

 What are the signs that a patient’s disease is under control?

 No drugs or treatments have been conclusively shown to affect the mechanism of the progressive disease process. So as to change lifespan disease control may be defined as limiting risks such as recurrent thrombosis, heart attacks, stroke, internal organ thrombosis — which do limit lifespan – and at the same time, maximizing quality of life, minimizing quality of life issues, which may seem to limit life functionality or in any case enjoyment. It's important, as Dr. Mesa mentioned, for patients to work with knowledgeable doctors to keep these realities in perspective.

 How has quality of life been impacted with MPNs since they are a chronic condition?

better knowledge about what to treat. Perhaps, hardest for us patients to

 And so what are examples of long-term treatment options and what patients have to look forward to?

 In modern thinking, not treating without purpose is in itself a benefit. As Dr. Mesa mentioned, there are side effects even with the better modern treatments that are coming to the forefront or are here. As you know modern medicines that we already have most prominently at this instant, JAK inhibitors, can yield really important improvements and quality of life in those for whom they work, including me when I took one.

 What is the best way for patients to learn more about their long-term treatments

 Dr. Mesa has already mentioned some of the more common treatment options that some people can use for a long time, including phlebotomy, interferon formulations, JAK inhibitors, spleen reduction, quality of life improvements, as well as more traditional hydroxyurea. Usually one of these currently prescriptible options achieve any needed risk reduction and quality of life improvement. Those who have low instead of high blood counts like red blood counts, erythropoietin substitutes and some other medications can provide important relief, sometimes as a bridge to the only option that's designated curative which is bone marrow transplant.

 What would you say is the best way for patients to learn more or become better educated about their treatment options?

 Well of course everyone looks at the internet but it's important to learn and learn quickly, especially with the relatively rare disease, how to discern reliable information from people who know what they're talking about and who can prove it by letting you know just how they know what they say they know. So that even if you trust, you can verify. The way I like to say it is, in short, you must become an expert.

Moreover, how can support groups play a role?

 Well online support groups and in-person patient meetings can be very important. In the Internet age, we can find them. No longer do patients with any MPN have to feel alone and that's important to help inform treatment decisions and important for psychological health, which is a critical part of long-term quality of life. Let me add, I'm partial to the oldest and highest quality online MPN support group that I know of. One that I help run it's called MPM Net and can be reached via the link at MPNinfo.org or if you get stuck you can email me at MPNpatientgroup@gmail.com.

 To bring it all together what would you say is your biggest piece of advice for a patient with a myeloproliferative neoplasm?

 There's a lot out there. I guess I'd summarize by saying, learn what your new normal is. Appreciate it for all it's worth and try looking at it objectively, even as you get to know some of the MPN community to become acquainted with your new normal, don't pretend you're someone else or need to do what may have been appropriate for them. Live your life and live your new normal as they come along. Live your next new normal.

Recognizing a Rare Cancer: Myeloproliferative Neoplasms

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