Tag Archive for: Myelofibrosis

Evolving Myelofibrosis Treatment Options: What You Should Know

Evolving Myelofibrosis Treatment Options: What You Should Know from Patient Empowerment Network on Vimeo.

Myelofibrosis treatment and care is evolving quickly so it’s essential to understand your options and work with your healthcare team when making treatment decisions. In this webinar, Dr. Gaby Hobbs will discusses the latest updates in research and clinical trials, the role of new and emerging myelofibrosis therapies, and shares advice for accessing quality care.

Dr. Gabriela Hobbs is a hematology-oncology physician specializing in the care of patients with myeloproliferative neoplasms (MPN), chronic myeloid leukemia and leukemia. Dr. Hobbs serves as clinical director of the adult leukemia service at Massachusetts General Hospital. Learn more about Dr. Gaby Hobbs.

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Related Resources:

Is Stem Cell Transplant the Only Curative Option for Myelofibrosis?

Is Stem Cell Transplant the Only Curative Option for Myelofibrosis? 

Myelofibrosis Therapies in Clinical Trials | BET Inhibitors

Myelofibrosis Therapies in Clinical Trials | BET Inhibitors 

Choosing a Myelofibrosis Treatment Plan | Key Questions to Ask

Choosing a Myelofibrosis Treatment Plan | Key Questions to Ask 

Transcript:

Katherine:

Hello and welcome. I’m your host, Katherine Banwell. As patients collaborate on treatment decisions with their healthcare team, it’s important that they understand all of their options and how these options may be impacted by research developments. That’s why the Patient Empowerment Network created the Evolve Series, to arm you with the latest information and to help you feel empowered and confident during conversations about your care.  

In today’s program, we’re going to hear from an expert in the field about the evolving treatment landscape for myelofibrosis and discuss how you can play an active role in your care.  

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

Dr. Hobbs:

Hi, how are you? Thank you so much for inviting me today. My name is Gaby Hobbs. I’m the clinical director of the leukemia service at Mass General Hospital in Boston and the director of the MPN program at MGH as well. I conduct clinical trials as well as see patients with myeloproliferative neoplasms.  

Katherine:

Thank you so much for taking the time to join us today. We really appreciate it.  

Dr. Hobbs:

My pleasure.  

Katherine:

Before we get into our discussion, can you share with the audience how the field of myelofibrosis has changed over the course of your career? 

Dr. Hobbs:

Yeah, so it really has been a very exciting journey. So, when I was in medical school, I think that we basically had just discovered the JAK2 mutation.  

So, in the course of my own training and then my professional career, we’ve gone from myeloproliferative diseases being conditions where we really didn’t necessarily have a reason why people would get these conditions. Now not only do we know about the JAK2 mutation, but we know about many other mutations that patients can have. Then in 2011, the first JAK inhibitor was approved, ruxolitinib (Jakafi), and since then, three additional JAK inhibitors have now been approved, including pacritinib (Vonjo), fedratinib (Inrebic), and most recently, momelotinib (Ojjaara).  

So, the field has definitely advanced concretely in that regard. But we also just have much more information about how to diagnose these conditions and also how to treat them. Outside of the JAK inhibitors, we’re better at recognizing when patients need to go to get a bone marrow transplant. For example, and our outcomes with bone marrow transplantation have improved significantly. We also have many other treatment approaches that wouldn’t have existed before, and we also recognize that patients with MPNs live with a lot of symptoms. So, I think that we’re better at just the doctoring part of taking care of patients with MPN. So, definitely, the field has just really, really changed significantly in the last two decades. 

Katherine:

That sounds like it’s been a rapid change, really. There may be some confusion, Dr. Hobbs, among people wondering what is the difference between primary and secondary myelofibrosis? Could you describe the differences?  

Dr. Hobbs:

Sure. Great question. So, that term, primary and secondary, is actually used in medicine very frequently for the description of many conditions that are not that different. So, primary means a patient has myelofibrosis and did not have any myeloproliferative neoplasm, or MPN, before their diagnosis.  

So, they went to the doctor and the first diagnosis they received was a diagnosis of myelofibrosis. Now sometimes we suspect that a patient may have had another MPN previously, such as essential thrombocythemia or polycythemia vera, but they just weren’t diagnosed.   

What I mean by that is, you know, let’s say you meet a patient and you look through their chart and you see that five years ago or 10 years ago, they had really, really high platelets or very high red blood cell numbers. So, there you could say, well, you know, you were never diagnosed with ET or PV, but maybe you had that. So, you probably have secondary myelofibrosis, but the diagnosis, you know, that you come with to the doctor is myelofibrosis. So, secondary myelofibrosis means that you had an underlying condition before, meaning you were first diagnosed with one condition like PV, polycythemia vera, or ET, and then those conditions turned into myelofibrosis.  

And then we call that secondary myelofibrosis, meaning it is secondary to the primary condition, meaning ET or PV. One area of confusion that I’d like to be able to clarify also related to this is if a person has secondary myelofibrosis, they don’t have two myeloproliferative neoplasms or two conditions. It is one and the same. They just live on a spectrum and over time, they can turn into, one into the other. So, it’s not that you now have two diagnoses, it’s still the same condition, it’s just morphed a little.  

Katherine:

Okay, thank you for that explanation. I’d like to talk about the importance of a patient’s healthcare team. What are the benefits to seeking care with a myelofibrosis specialist, even if it’s just for a second opinion or a consultation? 

Dr. Hobbs:

Great question. I think that one thing that COVID has given us is the ability to have webinars like this, but also that you can seek second opinions more easily with the advent of telehealth.  

So, whereas before I think that getting that second opinion would have been maybe more challenging, perhaps now it’s easier. But to answer your question, these conditions are rare. Myelofibrosis in particular is even more rare than the others.  

The landscape, as I kind of alluded to in our initial question, has changed significantly in the last two decades. So, getting a second opinion, whether that’s, like you said, just for an initial consultation, and then you never see that person again. Or you end up having kind of two doctors, one that treats you for your day-to-day needs and an expert or specialist that sees you occasionally as things may change, which can be very beneficial for a variety of reasons. I think that the first one is to just hear hopefully the same information that your initial doctor gave you, but maybe from a different perspective. I think that’s always helpful when dealing with a new diagnosis.  

Second is, you know, a specialist may have access to clinical trials. Although that may not be the right thing for you when you first meet them, it may be something you would want to consider or may be appropriate for you later down in your treatment. So, being connected to somebody that has access to research is something that, you know, it opens a door.   

Katherine:

We’ve established that research in the field is moving quickly. What are new and emerging therapies that are showing promise?  

Dr. Hobbs:

Yeah, so the list is long and it’s getting longer. So, in addition to the fact that we now have four JAK inhibitors approved, which is worth just remembering that, because not that long ago we only had one, and one of them was just approved less than six months ago.  There are many new agents that are being studied in combination with the JAK inhibitors. This past year at the American Society of Hematology meeting, which is the annual meeting where we go to share our research and learn from our colleagues, there were two Phase III studies that were presented at the same time.  

I can’t remember, or I don’t think, but that has really ever happened before for myelofibrosis. One of them was with an agent called pelabresib, which is a type of molecule called a BET Inhibitor. And the other one was with an agent called navitoclax, which is an agent called a BCLXL-BCL2 inhibitor, which is a molecule that helps cells to undergo apoptosis or programmed cell death.  

So, these molecules were both combined with ruxolitinib. And we saw the results of the Phase III studies for each of these agents, and they were really quite exciting. The punchline for both of these studies is that they demonstrated that when you give two drugs as opposed to just one, the amount of patients that have a significant reduction in their spleen is doubled than when you give ruxolitinib in it by itself. So, for some of our patients that is a really meaningful number. You know, if you’re a patient that suffers from a big spleen, knowing that there’s a possibility of having two drugs that you can take to really shrink that spleen in a significant way, I think is very, very promising. On the symptom front, taking two medicines versus one medicine really didn’t seem to make a huge difference. I think we can analyze this in two different ways.  

We can see the negative or the positive side of this. So, on the negative side, well, it’s too bad that, you know, added medication didn’t help patients feel better. But on the upside, it’s also good that taking two medicines didn’t make people feel worse. Sometimes you can think of, you know, if you’re taking more medication, maybe you will feel worse. So, the jury is kind of still add on the significance of those results. But regardless, without getting into too much detail about these studies, I think it’s really exciting for myelofibrosis patients to know that there are two agents that are in Phase III testing.

That means that the next step is really consideration of FDA approval. So, when medications go through clinical trials, they go through earlier phase studies, Phase I, Phase II, and then finally they get to Phase III. A lot of work and effort has gone into these two compounds to try to get them to FDA approval. So, we’ll wait and see if in the next year or so we have new agents for the treatment of MF.  

In addition to these two, which of course are the most advanced, there really are a variety of other agents that are being tested. Those, for the most part, are still in Phase II testing. And similarly to the ones I mentioned before, most of the compounds, the way that they go into trials is first they start out showing that they’re safe by themselves, and then they get added to a JAK inhibitor.

So, far, because ruxolitinib has been the one that we’ve had around for the longest, most of these studies are being tested in combination with ruxolitinib. But we start to hear rumblings from clinical trials that perhaps some of the newer trials will consider using other JAK inhibitors as combination partners, which is a natural evolution. So, to name a few other agents, we have drugs like selinexor (Xpovio), and navtemadlin we have a PIM kinase inhibitor, a lysyl oxidase inhibitor, an LSD1 inhibitor, the list is long of all these different agents.  

Preliminarily, at least from the data we’ve seen from all of these compounds, I think there’s a lot of room for excitement. We see that combining these drugs together, the new agent plus the ruxolitinib, leads to a significant reduction in the spleen. And in some of these agents, we’re starting to see other endpoints. So, in addition to just looking at can we make patients feel better and can we shrink their spleens?

We’re starting to look at other things such as when we add these medications, do we see a reduction in the scarring or the fibrosis in the bone marrow? Do we see a decrease in the cells that have the mutation? Do we see the patients live longer? All of those things are endpoints in our studies that we really haven’t tested before. So, I think the field really will produce a lot of exciting data in the next couple of years.  

Katherine:

You mentioned clinical trials, and we will talk about those in a few moments, but are there innovations in technology that are accelerating myelofibrosis research?   

Dr. Hobbs:

So, the most obvious way to answer that question is simply that it’s much easier to diagnose myelofibrosis now, thanks to the ability to do genetic testing now much more easily than before. So, I think that previously, you know, getting JAK2 testing or testing for the other mutations was not as simple or would take a long time for the results to come back.  

Now, you know, I see even in the smallest of practices, ordering not just the JAK2 gene, but ordering what many of us do, which is like a panel of genes, where you test for a lot of the genes at the same time, has become almost commonplace. So, that’s really a meaningful advance in that it’s a technology that’s available and it’s no longer as prohibitively expensive as it was before.  

That doesn’t mean that some patients don’t end up getting charged in ways that doesn’t make any sense anymore, but that’s a conversation for another time. But I think just having the ability to make those diagnoses because of how easy it is now to test for these mutations is really very meaningful.

Outside of that, I mean, I would say that along with the improvement in the knowledge of what mutations patients have with myelofibrosis, we definitely have deeper ways of analyzing what genes are being expressed and in what cells they’re being expressed to really understand, you know, when do patients first get those mutations and how do those mutations change over time. So, we’re really diving deep into the actual biology of the bone marrow and there’s some studies that have demonstrated that patients may even have the JAK-2 mutation in utero, which is really, really fascinating. So, definitely a lot more understanding of the actual biology of how these diseases happen.  

Katherine:

Dr. Hobbs, a key part of research moving forward is the clinical trial process. Can you talk about the benefits of patient participation? 

Dr. Hobbs:

Yeah, so I think to answer that question, I should preface that by saying that I conduct clinical trials, and so certainly my answer is going to have that as a bias, so it’s important to know that. And I tell my patients that as well when I’m talking to them about clinical trials. Now, why do I think clinical trials are beneficial? Well, there’s really no way to advance the field without the sacrifice that patients do by allowing us to conduct clinical trials. Without clinical trials, we cannot get drugs approved. Without new drugs, we certainly can’t help our patients anymore with newer therapies. That being said, a clinical trial is something that is not just an experiment. Many times patients will be like, well, I don’t want to be a guinea pig. And I completely respect that.  

So, I think it’s really important to recognize too, that we take conducting clinical trials very, very seriously. The machinery that needs to exist in each hospital to conduct trials includes a ton of people. So, we have a lot of regulatory bodies, both within the hospital and outside of the hospital, to ensure that clinical trials are conducted in an ethical and in a safe way. So, one of the benefits, which you may not consider when you’re contemplating participating in a trial, is that your care team actually becomes much larger. You’re much more closely scrutinized actually, when you’re a member of a trial.

So, whereas before you would have just primarily seen me and my nurse practitioner, when you participate in a clinical trial, all of a sudden you have all these research nurses that are calling you, checking in with you, making sure you’re feeling well, et cetera. So, that’s actually a nice perk to participating in trials. So, an important thing to know with clinical trials is that they may not benefit everybody. 

And that not every clinical trial may be right for you and that there may be times when trials are appropriate and times where trials may not be appropriate. So, it’s not a decision that you make that’s black and white and that’s a decision that you make forever. I think it’s something that you can continue to discuss with your care team as you go through having this disease.  

Katherine:

Let’s move on to treatment. Would you provide an overview of the currently approved therapies for myelofibrosis?  

Dr. Hobbs:

Sure, absolutely. So, I’ve alluded to this a little bit. So, in 2011, we had the first JAK inhibitor approved called ruxolitinib, the brand name is Jakafi. After that, we had the approval of Inrebic or fedratinib and then pacritinib or VONJO, and then most recently momelotinib or Ojjaara. So, we have four different JAK inhibitors that are now approved for myelofibrosis.  

So, who needs to get a JAK inhibitor and how do we choose between the JAK inhibitors? So, the traditional indications for JAK inhibitors are, does a patient have bothersome symptoms from having a big spleen? Does a person have symptoms from their disease? Symptoms can include things like night sweats, itching, unintentional weight loss, brain fog, and fatigue. Fatigue can be challenging because of course many things can cause fatigue. But those are some of the symptoms that can occur with having this disease. So, if a patient has both splenomegaly symptoms or one or the other, they’re eligible for a JAK inhibitor.  

So, just having myelofibrosis doesn’t mean that you need to have a JAK inhibitor right away. Probably the most commonly used JAK inhibitor, and this will be the case probably for a long time, is ruxolitinib.  

The reason for that is that it’s been around for a long time, and it’s a very well-tolerated medication. Patients that have platelets that are very low, meaning platelets that are less than 50, should be considered for pacritinib first, as that’s the indication for that agent. Patients that don’t do that well on ruxolitinib initially, let’s say that the dose gets increased and the spleen and the symptoms are still present, but still have good blood counts, are good candidates for then receiving fedratinib. Fedratinib can also be given upfront. It rarely is given upfront, simply because ruxolitinib has been around for longer and it’s a better-tolerated medication. So, therefore most providers feel more comfortable giving that upfront. I have had some patients that are concerned about the weight gain that is a side effect of ruxolitinib. For those patients, I’ve occasionally considered giving fedratinib first before ruxolitinib. And then lastly, we have momelotinib. It’s approved primarily for patients with myelofibrosis and anemia.  

Now momelotinib is still a JAK inhibitor, so it can still improve symptoms, and it still improves spleen size. So, I struggle with that recommendation of just using it for anemia in patients that don’t have splenomegaly or symptoms.  

But the FDA label was pretty broad, and it’s important to recognize that. So, how is momelotinib being used? It can be used in the upfront setting for patients that have spleen and symptoms, and also anemia, meaning low red blood cell levels. Or,  it can be used for patients that have been treated with a JAK inhibitor first and then develop anemia. So, momelotinib is given to continue to improve the spleen and symptoms, but also help the anemia. So, that’s kind of like an overview of the four JAK inhibitors. Now we have a group of patients that maybe doesn’t have a lot of spleen symptoms or symptoms in general but has issues with having low hemoglobin. So, for those patients, we’ve used a variety of different medications, including medications that are called erythropoietin, which is a hormone that helps to boost the red blood cell levels.  

A medicine that’s similar to testosterone that can also help boost the red blood cell levels called danazol (Danocrine). And then there’s a medication called luspatercept-aamt (Reblozyl) that has been approved for a related condition called myelodysplastic syndrome. And in some clinics, it can be used even though it’s not approved either by itself or in combination with ruxolitinib. And then lastly, patients that have what is called high-risk myelofibrosis, meaning they have some mutations that may indicate that a patient has a higher risk of having complications of their disease, or they have very low blood counts, are usually considered high-risk. Those patients should be recommended and referred to transplantation as soon as they’re identified as having high-risk disease.  

Katherine:

When you say transplantation, you’re referring to stem cell transplant. 

Dr. Hobbs:

Yes, and I’m glad you said it that way actually. So, stem cell transplantation or bone marrow transplantation, same thing, interchangeable, same procedure. You got it.  

Katherine:

Yeah. So, where do clinical trials fit into a treatment plan? 

Dr. Hobbs:

So, it really depends on what is available at the site where you’re seeking care. Clinical trials come in a variety of different flavors. So, there may be a clinical trial for patients that are newly diagnosed, that are about to start a JAK inhibitor, for example.  

So, if you’re a patient that’s considering a JAK inhibitor to treat your spleen symptoms or your systemic symptoms, and there happens to be a clinical trial for adding on another medication, like the first JAK inhibitor you receive, well, that’s a great place to consider a clinical trial.  

There may also be clinical trials in later lines. Let’s say you were treated only with a JAK inhibitor first, but the study that’s available at your center is adding another medication to the JAK inhibitor if the JAK inhibitor by itself didn’t quite do the trick. 

There’s also other studies, for example, at the time of transplantation, for example, using the JAK inhibitors during transplant. So, really the clinical trials can be relevant at any time during treatment. In addition to clinical trials, testing new medications, there’s also other ways to participate in research throughout your time as a patient with your care team, which may include things like, for example, consenting to participate in a tissue bank.  

You donate a sample of your blood or bone marrow that is then later on used for research. Or we may have studies investigating the symptoms a patient has throughout their disease or their experience living with their disease. So, there’s many different ways of participating in research and clinical trials, even if those don’t necessarily include trying a new medication.  

Katherine:

What questions should patients be asking if they’re interested in learning more about clinical trials?  

Dr. Hobbs:

Yeah, great question. So, the first is understanding, you know, what is the medication that you will be receiving? Are you going to be receiving a placebo? Is that an option? This means a sugar pill. That’s a common question that I get. How do you get assigned to different groups? So, in one trial, there may be a group that gets one dose, another group that gets another dose, et cetera. So, it’d be important to know how are you going to get assigned and what are the options potentially for you before you sign up. After that, it’s important to know what phase the study is in.

So, is this a first-in-human study where your doctor may not be able to tell you a whole lot about what’s expected in terms of side effects or safety or toxicity? Or is this a Phase III study where maybe the trial has been open for many years and there’s been many patients that have been enrolled in it already? Or maybe this is a drug that’s already been approved for another condition and we’re borrowing it for myelofibrosis, for example, and then your care team can tell you lots of information about the safety and toxicities, etc.  

So, having a sense of where the drug is in its development, I think can be very helpful. Then there are some practical things that we sometimes do not spend enough time talking about.  

So, I’m glad to have the space to talk about that here. Participating in a clinical trial takes time. And it’ll take more time as a patient to participate in a clinical trial than to receive regular care. You may have to go to the hospital where you’re being treated more frequently. If you’re somebody that receives virtual care where some of your visits are telehealth and some of them are in person, you need to be aware that you may have more visits that are in person because the clinical trial procedure requires that certain labs or tests be done in the facility, not anywhere else. Clinical trials by definition, unfortunately, sometimes have to be very inflexible in order to ensure that we collect data in a uniform way.  

So, just being aware that it may take more time to participate is important. And along those lines, asking if the clinical trial will reimburse you for some of that time. So, for example, if you need to park in the expensive hospital parking more frequently, some trials will actually reimburse you for that. Or they may offer a hotel reimbursement if you need to travel from far away and spend a night there. So, don’t be afraid to ask those things because many times that’s built into the clinical trial.

So, that’s an important thing just practically to know. So, asking for a study calendar so you get a sense of how frequently you’ll need to be going to the doctor is really important. Also, then realizing that potentially you may have to go to see the doctor or the care team more frequently initially, but then after the first couple of months, if everything is going well, you’ll likely have the flexibility to go less often. So, all those questions are important to have in mind.  

Katherine:

That’s great information, thanks, Dr. Hobbs. When considering therapy, how do you approach a treatment plan for someone diagnosed with myelofibrosis?  

Dr. Hobbs:

Great question. So, when approaching how I care for a patient with myelofibrosis, I take several things into account. The first thing is, who is this patient? What other medical conditions do they have? How impacted are they by their myelofibrosis? Then what I like to do is to plug in the numbers of the patient, their blood work, their mutations, etcetera, into one of the many risk calculators that we have to determine what the risk of their myelofibrosis is. 

If a patient is considered high-risk, I will generally consider transplantation or discuss a referral to a bone marrow transplantation in one of our first visits, if not the first visit. After that, I need to determine whether or not the patient has symptoms from their disease, and if so, if they should receive a JAK inhibitor. Then I’ll look through their blood work, what their symptoms are to decide which JAK inhibitor to use first.  

If really the spleen and symptoms aren’t the primary issue, if it’s more related to low blood counts, then we can think about treatments directed at improving the hemoglobin, for example. There may be a group of patients that don’t actually require any treatment when I first meet them. So, just providing them with education, what to expect. Then discussing more of the psychological impact of living with a condition and approaches to handle that, maybe more the focus of my care.

And in general, for most of my patients, we also talk about the rest of the care. So, not just what the blood work is and what medicine I’m going to start them on, but also other things that they can do to take care of themselves, including making sure that they are actively monitored by their primary care doctor or by other specialists if that’s still appropriate. You know, one of the things we don’t discuss that frequently in myelofibrosis, we discuss that more often in essential thrombocythemia or polycythemia vera is a risk of blood clots.  

But the truth is that myelofibrosis patients can also have risks of blood clots. So, therefore, making sure that patients with MF that may have issues like hypertension, diabetes, high cholesterol, etc., get those well-managed is also really important to prevent them from having blood clots. So, lifestyle management is also an important part of the care of a patient with myelofibrosis. 

Katherine:

That’s all great advice. A note to our viewers, PEN has also created downloadable office visit planners to help you organize your thoughts and communicate effectively with your healthcare team. You can find those in the MPN Toolkit at powerfulpatients.org or by scanning the QR code on your screen.  

Well, it’s been a lot of great information, Dr. Hobbs, and I’d like to close with your thoughts on the future of myelofibrosis care. Where are we headed and what would you like to leave our audience with?   

Dr. Hobbs:

Well, the first thing I wanted to say is just kind of piggyback with what you said about the visit planner. I love that. I think that many times patients come to a visit and they’re like, oh, I had this question that I wanted to ask you and now I can’t remember what it was. And especially if you’re seeing a doctor every six months or something like that, making sure that you come to that visit prepared with lots of questions is an excellent way to make the most use out of your visit with your provider. So, I definitely encourage you to do that. In terms of what to leave patients with, so going back to what we were discussing initially, the list of new agents that are being investigated for myelofibrosis is long and longer by the day. So, as a myelofibrosis doctor, I really feel very optimistic that in  the next year and hopefully in the next couple of years, we’re going to have a variety of new treatment options that are going to really help our patients to live not just longer with their myelofibrosis, but truly to live much better with their myelofibrosis.  

So,  continue to get informed by watching webinars such as this one and reading reliable sources of information on different patient advocacy organizations because there’s really a lot of changes that are happening. So, I definitely think it’s a time to feel hopeful about the future of  myelofibrosis.  

Katherine:

Well, thank you so much for taking time to join us today, Dr. Hobbs, we really appreciate it.  

Dr. Hobbs:

Sure, it’s always a pleasure.  

Katherine:

And thank you to all of our collaborators. 

To learn more about myelofibrosis and to access tools to help you become a proactive patient, visit powerfulpatiens.org. I’m Katherine Banwell. Thanks for joining us.   

Evolving Myelofibrosis Treatment Options: What You Should Know Resource Guide

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Thrive | What You Should Know About MPN Symptoms & Treatment Side Effects

Thrive | What You Should Know About MPN Symptoms & Treatment Side Effects from Patient Empowerment Network on Vimeo.

How are MPN symptoms and treatment side effect managed? In this animated explainer video, an MPN specialist and myelofibrosis patient discuss the importance of clear communication with your healthcare team, the process for assessing common issues, and advice for advocating for yourself.

 

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Transcript:

Brian: 

Hi, I’m Brian. Nice to meet you! I’ve been living with a condition called myelofibrosis for many years. While there have certainly been ups and downs, I’ve been able to navigate care for my condition and to live a full life.  

So how have I been able to do that? First and foremost, I have a great relationship with my care team, whom I communicate with regularly. Meet, Dr. Liu – my doctor. 

Dr. Liu: 

Hi! I’m Dr. Liu, and I’m a hematologist and a specialist in myeloproliferative neoplasms or MPNs. The three types of MPNs are essential thrombocythemia, or ET,  polycythemia vera or PV, and myelofibrosis, or MF.  This group of blood cancers is characterized by the bone marrow overproducing a certain type of cell.  

Maintaining a good relationship with your healthcare team, coupled with finding a treatment approach that works for you, can help you live a full life and to thrive with an MPN. 

Brian: 

Exactly, Dr. Liu. Over the years, I’ve experienced periodic issues with my condition. I’ve had symptoms and treatment side effects that have been bothersome and interfered with my life. But, communication with my team has been essential to feeling well.  

Dr. Liu: 

That’s right, Brian. When symptoms or treatment side effects are bothering you, it’s important to let your healthcare provide know how you are feeling. 

Brian: 

For example, recently I felt tired beyond general sleepiness. And when I shared this with Dr. Liu, we discussed potential causes of the fatigue, and we talked in-depth about my options to manage it, including changing therapy and some simple changes to my diet and lifestyle.1 Over time, my energy levels improved, but having the open dialogue with Dr. Liu was essential to tackling this symptom head-on. 

Dr. Liu: 

That’s a great example. When I first hear from a patient that they are having an issue, we go through several steps to find a solution.2  

We start by ensuring that the disease is well-controlled, so we check blood counts. Next, we try to determine if it is a symptom of the MPN or a side effect of the treatment. Once we’ve done those steps, we come up with potential solutions which may include, but are not limited to: 

  • A dose reduction or a treatment holiday. 
  • Changing therapy to find something that is more well-tolerated. 

Other considerations are dependent upon the specific symptoms and side effects but may include: 

  • Supportive care options, including diet and exercise. 
  • A visit to your primary care doctor to see if there is something else going on physically. 

Brian: 

That’s good to know, Dr. Liu. Something you brought up with me, which I feel is important to mention, is mental health. Often, emotional symptoms can take a toll on the body, causing fatigue or other issues. 

Dr. Liu: 

Great point, Brian. Seeking care for your mental health is crucial, particularly if you are in active treatment. 

Brian: 

Of course, we know that the symptoms and treatment side effects for MPNs can vary widely, so what advice do you have for patients who may be afraid to speak up? 

Dr. Liu: 

The most important thing to remember is that we have options to help you, no matter what you are going through. It’s your body and if you don’t let your provider know what you’re going through, they can’t help you. 

Brian: 

So true. It’s also a good idea to bring a care partner along to appointments, sometimes a spouse or friend can you help you communicate what’s going on. 

Dr. Liu: 

That’s great advice, Brian. Bringing someone along to take notes is a great idea. Also, be sure to write down any questions or concerns you have in advance to make the most of your appointment. 

Brian: 

OK, Dr. Liu, let’s recap your advice for MPN symptom management: 

Dr. Liu: 

Good idea! First, remember that everyone’s MPN is different, so managing symptoms and side effects can be tricky. Communicating with your healthcare team is critical to your overall care – report any and all concerns to your team immediately. 

And, do your part. Make sure you see your primary care physician regularly and do your best to maintain a healthy lifestyle. 

Brian 

And, most importantly, remember you are at the center of your care. Never hesitate to share your opinion and to advocate for yourself. 

To learn more, visit powerfulpatients.org/MPN to access a library of tools. Thanks for joining us! 

Thriving with an Myeloproliferative Neoplasm (MPN) Resource Guide

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How Molecular Markers Affect MPN Treatment | Advances in Research

How Molecular Markers Affect MPN Treatment | Advances in Research from Patient Empowerment Network on Vimeo.

Are there new molecular markers being discovered that could affect myeloproliferative neoplasm (MPN) care? Dr. Lucia Masarova explains common MPN driver mutations and what researchers are learning about recently discovered molecular markers, such as ASXL1.

Dr. Lucia Masarova is an MPN Specialist and Assistant Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Masarova.

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Expert Perspective | Disease Modification in Polycythemia Vera

Expert Perspective | Disease Modification in Polycythemia Vera


Transcript:

Katherine Banwell:

Dr. Masarova, molecular testing is important for people diagnosed with MPNs and may help provide insight into effective treatment approaches. What are some new areas of research related to molecular markers? 

Dr. Lucia Masarova:

Molecular markers are very relevant in our designs or thinking about myeloproliferative neoplasms. Not only treatments, but also the disease qualification or prognostication wherever since the discovery of the so-called driver mutations, which are the mutations responsible for the overproduction of the blood counts and disease pathogenesis.  

Among them we have the most common, JAK2 mutation, then also calreticulin, MPL, or in some instances we don’t even understand and call it triple-negative. 

There we have learned, over the years, that the amount of the expression, or allele burden, does correlate with the disease behavior outcome. And then our ability to reverse that. So, a chief decrease of the burden is also relevant to the outcome of the patients. So, developing therapies or even putting these as an endpoint for clinical trials is important for our decision-making and moving towards eradication of the disease.  

Then there are additional molecular changes, which include non-drivers, which are additional mutations that we have learned and even implemented in the latest prognostic models, some of them are very unfavorable, such as ASXL1, Ezh2, IDH mutations, certain splicing factors.  

And those play additional roles, a lot of it we still do not understand, in how the disease is going to ultimately behave. What is their interplay, and how we can interfere with that?  

So, learning about the impact of these mutations and the drivers and the other effects that cause the disease evolution will probably become the landmark of this decade and in facing myeloproliferative neoplasms. 

And I’m hoping we will develop medications, or we will be able to focus our efforts and our decision-making based on molecular definition, as it’s currently very broadly seen across all cancers. We call it precision medicine where we really define, “How does this look like,” not how we box it in based on morphology. What is it driving? What is it not responding? And what can we do to improve that?  

So, I totally see here a big potent and powerful tool to allow us to make the most individualized and customized decisions for our patients to offer them the best outcomes.  

Expert Perspective | Disease Modification in Polycythemia Vera

Expert Perspective | Disease Modification in Polycythemia Vera from Patient Empowerment Network on Vimeo.

Is it possible to change the course of disease in polycythemia vera patients? MPN specialist and researcher Dr. Lucia Masarova shares an overview of the research in disease modification, discussing her work as the coauthor in an article entitled Moving Towards Disease Modification in Polycythemia Vera, recently published in the journal Blood.

Dr. Lucia Masarova is an MPN Specialist and Assistant Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Masarova

 

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How Molecular Markers Affect MPN Treatment | Advances in Research


Transcript:

Katherine Banwell:

Dr. Masarova, you are a coauthor in an article entitled Moving Towards Disease Modification in Polycythemia Vera, which was recently published in the journal Blood. Can you share some of the highlights of the article and what it means for PV patients? 

Dr. Lucia Masarova:

Disease modification in polycythemia vera. I’m so excited finally being talking about this because we’ve been really, really, really so hungry for this term, although we still don’t know what it means.  

So, we group together with lots of experts in the myeloproliferative neoplasm field and try to brainstorm and put together, “What does it actually mean?” And to me, and to all of us, it was to offer our patients the normal or not-normal lifespan without the consequences of the disease that they face. Because we historically divided polycythemia vera into high-risk or low-risk disease based on the age or previous history of thrombosis or clotting complications.  

However, there is a huge area of patients that wouldn’t have either, and still suffer tremendously a bad quality of life, and ultimately also face the disease progression to myelofibrosis, which is the most actual complication of long-term polycythemia vera duration.  

So, the concept of disease modification would be to actually prevent the complications to even occur. To allow our patient to live free of having the fear of living with a thrombosis or clotting complication or ultimately progress into myelofibrosis. We have to learn how to get there. What are the relevant endpoints of tools for us to utilize to really understand? We have learned a lot from seeing what we call molecular remissions, or control of the JAK2 mutation with certain medications, for example, interferons or latest ruxolitinib (Jakafi), the JAK inhibition, where the decrease of the allele burden, which represents the disease, is correlated with better outcome.  

So, that is something that we have to be learning down the road with a longer follow-up. But that basically triggered us to focus on what can we do better? How do we prevent this from even happening rather than only controlling the historically main points of the disease which are presented by the blood counts symptoms and display? And where we are actually failing quite a lot of patients because despite them having a control count, they still don’t have a happy life, and lots of them suffer and complain.  

So, this is something to be learned, and this is opening the disease modification not only for polycythemia vera, but also for all patients with myeloproliferative neoplasms, which have a little bit of a different feeling in the whole myeloid malignancies field. Because it is a very long disease, and it could evolve and change, and only now we starting to understand what does actually happen there. Why some people could live for 30 years, and never face any consequences, and the others would progress very fast? 

So, disease modification would normally allow us to develop and learn more tools and better biomarkers, but also focus on drugs that are really needed to help with these long-term outcomes of our patients.  

Myeloproliferative Neoplasm News and Research Updates

Myeloproliferative Neoplasm News and Research Updates from Patient Empowerment Network on Vimeo.

Dr. Lucia Masarova, a myeloproliferative neoplasm (MPN) specialist and researcher, discusses the latest updates from a recent MPN Congress. Some of the highlights include new learnings in hematopoiesis, JAK inhibitor comparisons, interferon therapy, and the potential for combination treatments in the future.

Dr. Lucia Masarova is an MPN Specialist and Assistant Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Masarova.

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Advances in Research | Emerging MPN Therapies on the Horizon 


Transcript:

Katherine Banwell:

Dr. Masarova, you were in New York recently for the MPN congress. Can you share some highlights from that meeting? 

Dr. Lucia Masarova:

Yeah. Sure. That was a very interesting and very loaded conference full of experts and great data. I really liked the overall excellent update of all the therapies that currently exist in the MPN space, including polycythemia vera, essential thrombocythemia, myelofibrosis. So, really a broad breadth of JAK inhibitors, their current sequencing, combinations, interferon update. I very much like also the focus of the novel therapies, which actually talked about, for example, the development of the antibody against mutant calreticulin, PIM inhibitors, and a couple others. They are very promising in the space. 

There were also very, very relevant clinical data. I think I really, really enjoyed the radiation in hematopoiesis topic. It spurred lots of discussions in the room. And also, fantastic talks about clonal hematopoiesis and its role in patients with myeloproliferative neoplasms and cancers.  

Overall, very great data on artificial intelligence because that will be a very needed tool, but also a very worrisome tool, at this point, until you learn how to use it to help our patients. But that showed a very promising effect and ability for us to, for example, predict thrombosis risk in polycythemia vera patients or to distinguish patients with ET versus prefibrotic myelofibrosis, which is still subject to lots of basically subjective analysis from hematopathologist.  

And also, the poster section was quite striking and really excellent. You could walk around and see so many interesting data. The match and direct comparisons of JAK inhibitors, particularly the latest approved, momelotinib (Ojjaara), as it compared to safety data which do currently exist in fedratinib (Inrebic) or pacritinib (Vonjo). 

Katherine Banwell:

When it comes to MPN research and emerging treatment options, what are you excited about specifically? 

Dr. Lucia Masarova:

There is a lot of excitement in the field currently, and it really depends how we put these patients in, as I would call, boxes, but I don’t like the term. We have these less aggressive diseases, such as polycythemia vera and essential thrombocythemia.  

Where I’m really excited about the role of interferon, with the approval of ropeginterferon (Besremi), or ropeginterferon in United States as well as Europe, we have opened a door for learning how can we do better.  

It is approved for polycythemia vera patients. There are currently clinical trials running in essential thrombocythemia patients, within patients with prefibrotic myelofibrosis. That’s an agent that has an ability to go after the disease clone and hopefully, hopefully eradicate or prevent it. Especially, especially exciting in the terms of preventing it for progression.  

Then iron metabolize modifier, hepcidin mimetics, other agents impacting this. It’s very important we finally learn how iron plays the role in these patients and how we can actually improve. Very important area in helping patients requiring phlebotomies and hopefully, hopefully altering the whole disease outcome in the long-term. 

For myelofibrosis we live in an era of JAK inhibitors. We are so excited to have four currently approved and we’re looking forward to the combinations where we have now safer and less cytopenic agents that have a role in anemia or thrombocytopenia and hopefully will be able to be combined with others. 

So, we could even move the field more into other hematologic malignancies, where in myeloma we use five, six, seven, eight drugs. For myelofibrosis, we still have one. So, I think we have still a lot to do. 

And then non-JAK inhibitor combination. Non-JAK inhibitor, a compounds or mechanism of action really tailored to the disease pathogenesis. Calreticulin, excellent topic, which I’m saying maybe in couple years we will be really classifying myeloproliferative neoplasm calreticulin-mutated, but also JAK2-mutated, and we will not be calling them one because hopefully we will find a tool to eradicate calreticulin and to really be able to offer ultimate – what I call ultimate cure.  

So, that’ll be something really exciting to come and all of these investigators in MPN fields are so eager to see what – whether the preclinical data we have seen are going to stand in our patients. And that would be really fantastic.   

Choosing a Myelofibrosis Treatment Plan | Key Questions to Ask

Choosing a Myelofibrosis Treatment Plan | Key Questions to Ask from Patient Empowerment Network on Vimeo.

When considering therapy for myelofibrosis, where do you start? Dr. Lucia Masarova shares advice and key questions to ask your provider when making myelofibrosis treatment decisions.

Dr. Lucia Masarova is an MPN Specialist and Assistant Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Masarova.

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Transcript:

Katherine Banwell:

When considering treatment options, what key questions should patients ask about their proposed treatment plan? 

Dr. Lucia Masarova:

What’s the goal of my therapy? That is one of the most important things to know. Patients don’t even know how long they have to be on the medicines. What to do and how does it look when the medicine is still working? What do I need to be looking for in this medicine? And then what are we going to do if it fails? And what does it actually mean when it fails? What is the schedule? How burdensome the treatment is? How often do I have to come?  

How often and what do I have to pay? Because the financial burden we have to really, really face the truth. It is very, very, very significant and somebody living with this disease predicates. It’s something we cannot take lightly, and we really have to combine our efforts and help with that. There are fantastic patient support organizations, but is not well-known, and is still in the rare – in rarer field. So, there’s more effort that we do. 

When do I need more help? Where to be referred to more experts? What is the role of stem cell transplantations, if ever? So, those are really the key things.  

Where do I find reliable resources to learn about my treatment, to learn about the disease? How do I connect with people from the same community? It is a disease with a lower age in a lot of circumstances and really facing this disease in the 30s or 40s or 50s is a really challenging thing. Although we have more and more medications currently, we really do have now to start thinking about their durability, about the safety for long-term, about their assessments for not performing, and where do we place the ultimate cure for stem cell transplants?  

And how do we make it actually happen in more and more eligible patients? Because we have to face the truth. It is still not utilized to where it belongs. Patients are not being referred. 

Patients are not being transplanted. And they may change with novel therapies. But we have to really consider all of our tools to offer the longest life span and to prevent all the disease trouble that comes with living with MPNs.   

Katherine Banwell:

When it comes to clinical trials, where do they fit in in choosing treatment? 

Dr. Lucia Masarova:

For me, it’s number one., and always number one.  

That’s just the academic centers which are dedicated and focused on developing better and novel and up front and just tailored and customized drugs. But I know that the life is out there and it’s a little bit more challenging for everybody to deal with such a rare disease.  

I would definitely say any patient that does not respond to current therapy in terms of uncontrolled symptoms or spleen, or other concerns should be referred and evaluated for participation in clinical trials. It is the only way we could understand what is driving that this is not responding and how could we help the best?   

For patients with myelofibrosis, which is the most aggressive myeloproliferative neoplasm, I would definitely put it in. If they are not doing well on number  one, JAK inhibitor, whatever is being used, they should be highly encouraged to be referred to centers and evaluated for clinical trials. 

We have been developing as others and own strategies to potentiate the benefit and efficacy of the current treatments, as well as agents in what we call salvage or refractory setting.  

However, I cannot emphasize enough to really focus on the first track that providers choose for their patients and utilize it to the best ability to avoid frequent or quick switching. Because in a salvage or  refractory setting we cannot offer the same benefit we could offer upfront. We are pushing the disease, maybe being less responsive, maybe more refractory, if we don’t handle the medication we have currently on the table to the best ability.  

Those are excellent medications, fantastic drugs, but there are shortcomings in each and every one of them. And we could do better to really start thinking about what has happened with the medication, why is it failing the patient, and what else could we do? And that’s only possible in the clinical trial setting, especially in such a rare disease as myeloproliferative neoplasms are.   

Katherine Banwell:

Why is it important for patients to feel like they have a voice in their treatment options? 

Dr. Lucia Masarova:

Because it’s about the patients. I would say, as I always say to my patients, “Nobody’s a better advocate for you than you.” I really, really, really like working with patients. They are educated. They understand where to find resources. They’re not afraid to ask. That challenges all of my team and everybody to really be engaged. They know when to notify me. Not to be quiet when they need something. And really raise their voice when something doesn’t work.  

Patients know their bodies more than anybody can. And no data, no boxes, no books can ever tell me how it actually is. It’s not by chance we have two ears to listen and one mouth to talk.  

So, we have to really listen what the patient has to say and take all the abilities, the resources, the knowledge, the capabilities to really make the best thing for the patients, because it is ultimately and only about that.  

Is Stem Cell Transplant the Only Curative Option for Myelofibrosis?

Is Stem Cell Transplant the Only Curative Option for Myelofibrosis? from Patient Empowerment Network on Vimeo.

Is there a cure for myelofibrosis? Dr. Lucia Masarova explains the role of stem cell transplant for the treatment of myelofibrosis and reviews additional therapies for patients who do not qualify for the procedure, such as JAK inhibitor therapy.

Dr. Lucia Masarova is an MPN Specialist and Assistant Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Masarova.

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Myeloproliferative Neoplasm News and Research Updates

Transcript:

Katherine Banwell:

Dr. Masarova, stem cell transplant is sometimes recommended for people with myelofibrosis. Is this still the closest option to cure for those patients? 

Dr. Lucia Masarova:

I would say so, as much as we don’t like it. We would like to develop novel conservative, less aggressive, that we call procedures or drugs. Stem cell transplants still represent a long-term cure for patients that are eligible. 

Katherine Banwell:

What about for patients who don’t qualify for stem cell transplant? What are effective long-term treatments for them? 

Dr. Lucia Masarova:

That’s a very, very important question and topic. The key point here is the long-term because long-term is a little difficult term in conservative management of myeloproliferative neoplasm, particularly when it comes to myelofibrosis.  

With the development of JAK inhibitors, the longest experiences we have with the first one called ruxolitinib or Jakafi, we have seen prolonged outcomes in survival so patients could live longer than expected before.  

However, it’s not forever. So, that’s why we are trying to develop novel strategies where I see a lot of roles of combinations of JAK inhibitors and other correlative compounds, such as bromodomains inhibitors or hypomethylating agents or others that would affect the pathways that we are missing currently to cover with the JAK inhibition. And that ultimately leads to medication failures and patients being refractory and then having a shortened lifespan.  

So, I’m hoping we will develop something for long-term. Particularly promising a very, very interesting concept is with the calreticulin where we are developing monoclonal antibodies or vaccines because we have seen and discovered calreticulin driver to be a targetable thing that causes immunogenicity. 

But I do really hope that we will move forward with these discoveries and the JAK mutate or other drivers causing myeloproliferative neoplasms to offer long-term management.  

Myelofibrosis Therapies in Clinical Trials | BET Inhibitors

Myelofibrosis Therapies in Clinical Trials | BET Inhibitors from Patient Empowerment Network on Vimeo.

What are BET inhibitors? Dr. Lucia Masarova, an MPN specialist and researcher, explains what BET inhibitors are and discusses the role these therapies may play in the treatment of myelofibrosis.

Dr. Lucia Masarova is an MPN Specialist and Assistant Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Masarova.

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How Molecular Markers Affect MPN Treatment | Advances in Research

How Molecular Markers Affect MPN Treatment | Advances in Research

Transcript:

Katherine Banwell:

We’re starting to hear more about BET inhibitors. Could you explain what they are and how they work to treat myelofibrosis? 

Dr. Lucia Masarova:

BET inhibitors are abbreviations for bromodomain inhibition, which is a very relevant regulator of transcription factors that play a significant role for making the blood cells.  

So, just differentiation of red cells or platelets, as well as very significant role in cytokines regulation. We know that myelofibrosis is a disease that is defined by overactive JAK-STAT Pathway that ultimately leads to increased cytokines.  

However, there are other pathways that play a significant role, and one of the very major ones is NF-kB, where the BET inhibitor come in play because they target it and help us to decrease the cytokine load as well as alter the differentiational block that happens in the red cells or megakaryocytes or platelets in these patients. 

So, the combination of bromodomain inhibition, or even using it as a single agent on or after refractory I think is a very promising tool that excludes the only JAK inhibition that we’ve been developing for diseases and opens the door for combination strategies that we were so many years thinking through and trying to find out. 

This is really the most promising compound or way of altering the disease background that we can see.  

Expert Advice | Living and Thriving With an MPN

Expert Advice | Living and Thriving With an MPN from Patient Empowerment Network on Vimeo.

Is it possible to live well and thrive with a myeloproliferative neoplasm (MPN)? Dr. Naveen Pemmaraju, an MPN specialist and researcher, shares key advice for patients, stressing the importance of taking an active role in learning about their disease and communicating with their team to manage common symptoms and side effects. 

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

 

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Common MPN Treatment Side Effects |Strategies for Management


Transcript:

Katherine Banwell:

In your experience, what does it mean to thrive with an MPN?  

Dr. Pemmaraju:

Well, I really love that phrase so much because it’s meaningful to me.  

You know, you’re talking about something that resonates with me and my patients, which is not just living with the MPN, but you’re talking about thriving with an MPN. That’s so resonant to us. I think really, I would go for three parts to that.  

One is that it’s an acknowledgment or a complete understanding of the disease. So, not denial, the opposite of denial, whatever that is, Katherine. So, understanding as much as you can about the disease which is, I encourage people to Google, look up on the internet. I just, what I want you to do is couple that with talking about it in context with your provider. I think the worry that people have is you’re at your home midnight, you’re Googling stuff, it may or may not be right. So, anyway, so just do that, but then bring the information to the next visit. So, fully understanding and learning as much as you can in your own way. Number two is to be able to have a quality of life that is not just living with the disease, but actually being successful at your relationships, your work, whatever it is that brings you meaning and joy in life. And that sometimes has to do with the MPN paradigm, sometimes has to do with the other stuff we said.  

But I think, doing that, not despite the fact that you have the MPN, but acknowledging it with that, right? And then I think the third aspect is, if you have some way or some platform to be able to express yourself with the MPN because it’s such a rare disease, we think maybe only four out of 100,000 people worldwide get these. A lot of patients, not for everybody, by the way, but a lot of patients are thriving on support groups. 

It used to be you have to be in person, that’s very difficult to do with rare diseases. But now online, social media, a lot of different ways to get involved. Whether someone’s an introvert or an extrovert, whether someone wants to be private or public, all those things are hugely important, so it’s a personal decision. But for many, they want to get out there, and it’s not necessarily this scientific information exchange, although that’s good. But the support and encouragement and comradery of talking to other patients about what we’re talking about.  

It is, in fact, a little bit more facile to do it with the more common diseases, breast cancer, all of these things. And it’s much more difficult, social media online has opened that up. So, to me, I think that’s a kind of mix that I’ve been seeing in my patients. And that leads to empowerment. It leads to taking control of the things that can be controlled, leaving the things that can’t be controlled to what needs to happen. And then an understanding and anticipation of things that may happen in the next few visits, in the next few years. I think that’s how people can thrive with these MPNs.   

Katherine Banwell:

Dr. Pemmaraju, When it comes to living and thriving within an MPN, managing disease symptoms and treatment side effects is a big part of that. How can symptoms and side effects impact life with an MPN?  

Dr. Pemmaraju:

Katherine, I’m glad you asked about that because I think before we get into the science and the pathobiology and all these complex things, it really starts with the patient. And as you and your team and others have really noted, the MPN for many of our patients, it is a chronic, often lifelong journey. And we really need to reemphasize in this modern era, the patient-centered experience and the caregiver experience.   

And so I would emphasize a few things. One is that our MPNs are oftentimes so-called invisible diseases to other people. So, this phrase that just really is tough for us to hear for our patients and our loved ones, “Oh, you don’t look like you’re sick. You don’t look like you have cancer.” So, it emphasizes the internal part of the internal medicine, that’s one.

Number two, it reminds you that you cannot tell on the external what kind of a war, a cytokine war that is going on inside of a patient. And so even though the blood counts are normal, the spleen is okay, the treatment paradigm is going okay, we don’t know what’s really going on. So, that’s why our great friend and colleague Ruben Mesa invented and pioneered the MPN symptom burden to really nail down what’s going on.  

And then third is our treatments, Katherine, our treatments, while overall halting or stopping or helping the MPN can then introduce a whole other round of toxicity, side effects, and so we need to manage that.  

So, both the disease itself and the treatments, two separate entities, and that’s what we need to be monitoring in the clinic.  

Advances in Research | Emerging MPN Therapies on the Horizon

Advances in Research | Emerging MPN Therapies on the Horizon from Patient Empowerment Network on Vimeo.

The pace of research in myeloproliferative neoplasms (MPNs) is advancing rapidly, but what do patients need to know? MPN specialist and researcher Dr. Naveen Pemmaraju shares an update on the latest research and his optimism for the future of MPN care.

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.

 

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MPN Essential Testing | How Results Impact Care & Treatment Options


Transcript:

Katherine Banwell:

Dr. Pemmaraju, as a researcher, what are new and emerging therapies on the horizon in MPN care?  

Dr. Pemmaraju:

Well, Katherine, I’m glad you asked because I’m proud to tell you here, at the end of 2023, that we’ve now entered a new golden era of therapies for MPNs. Your group, and others, have led the way in advocating, but for so many years, honestly, we didn’t have many breakthroughs or new medicines. And now we literally have something we’re hearing about once a month. I think this golden era is divided into four buckets, Katherine, and that’s why I’m so excited for our patients and their caregivers. Number one is novel JAK inhibitors. So, beyond the approved ruxolitinib, fedratinib, and now pacritinib, we have a fourth one that’s under consideration, that’s called momelotinib.  Hopefully, we’ll have that approved by the end of the year. 

 [Editor’s Note: Momelotinib (Ojjaara) was approved by the U.S. Food and Drug Administration (FDA) on Sept 15, 2023 for the treatment of intermediate- or high-risk myelofibrosis, in adults with anemia.] 

And there are actually other drugs around the world. So, not just in the U.S. and North America that are being developed as a further JAK inhibitor. So, just like we’ve seen in CML with the TKIs for BCR-ABL after the imatinib (Gleevec) medicine, hopefully, we have seven to 10 choices for our patients.  

Number two is the combinatorial approach of a JAK inhibitor plus something else. And that’s a field that I’m personally very involved in and helping to lead. The concept there is you take the known workhorse drug, the JAK inhibitor, use it as the backbone, and then add in the second agent. We started to do those studies in patients who were already starting to lose a response and we added in the second agent, those were called suboptimal studies. And then now we’re moving those drugs into the frontline setting in international global randomized studies. So, stay tuned, let’s see how those go.

But the concept is, can you take a new agent, whether it’s a BET inhibitor, a bromodomain inhibitor, a Bcl-xL inhibitor, PI3 Kinase, et cetera, and combine it with the JAK inhibitor? The third bucket that’s even more exciting to many people is that of novel agents standing alone by themselves. Now you’ve had either a JAK inhibitor or some other therapy for your myelofibrosis. That didn’t work for whatever reason. Now you’re looking for a completely new strategy.   

An explosion of research, not just in the lab, which we’ve had for the last 10 years, but over the last three or four years, amazingly, even despite the COVID pandemic. I would say dozens, really dozens of trials that are what you would consider beyond or non-JAK inhibitor therapy. Some of them include telomerase inhibition, with the imetelstat agent, for example.

And so the concept here is, can you now hit the myelofibrosis in a completely different pathway? And the answer clearly is yes. And those results have been tested now in the lower stages, the earlier stages, Phase I and II. And you’re starting to see those drugs enter into the phase two and phase three. We eagerly await those results if there can be a viable beyond JAK inhibitor. And then finally, if that wasn’t exciting enough, there’s a fourth bucket, which is thinking about specifically the anemia myelofibrosis. We’ve never really historically done that. We’ve had older drugs, danazol (Danocrine), steroids, growth factor shots, blood transfusions.  

But now here you see both pharmaceutical interest, as well as academic interest, in developing agents that either specifically target the anemia of MF or both, the MF and the anemia. And that could be a game changer for our patients in the next five years. So, Katherine, a wealth of exploding research that I’m personally very excited about that gives me and our field hope, momentum, and enthusiasm going into 2024.   

Essential Thrombocythemia Watch & Wait | What Patients Should Know

Essential Thrombocythemia Watch & Wait | What Patients Should Know from Patient Empowerment Network on Vimeo.

What is watch and wait, and what does it mean for essential thrombocythemia (ET) patients? Dr. Naveen Pemmaraju defines this term, helps viewers to understand why it’s beneficial to wait before beginning treatment, and shares advice for managing the worry that can be associated with this time period.

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

 

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Increased MPN Symptoms | What Does It Mean for Patients

Increased MPN Symptoms | What Does It Mean for Patients?

Expert Advice | Living and Thriving With an MPN

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Advances in Research | Emerging MPN Therapies on the Horizon


Transcript:

Katherine Banwell:

Stephanie writes, “I have ET, and I’m not being treated. Do you have advice for the watch-and-wait period? I’m anxious about the disease changing and don’t know what I’m waiting for.” So, before you answer the question, Dr. Pemmaraju, would you define this term, watch and wait?  

Dr. Pemmaraju:

I will. And to Stephanie and everyone out there, this is a great question. I will say half the folks I talk to actually call it watch and worry, okay. Some people call it watch and wait, and as Stephanie’s saying, some people call it watch and worry.  

Yeah, the concept is threefold. One is that there are many cancers, many cancers, including blood cancers, that can be caught so early on that they don’t require treatment. A lot of patients with CLL, chronic lymphocytic leukemia, ET, as Stephanie mentioned, in the solid tumor. It’s very common to be diagnosed with a prostate cancer that’s low grade, early stage that can be observed. Number two is in ET, there is a science behind it.   

What we found in our studies, and they can be updated over time and you’ll see those, the traditional is that if you’re below the age of 60 and/or you’ve had no blood clot, thrombotic event, that’s considered low risk. And the treatment can be observation, perhaps adding in a baby aspirin to prevent against blood clots if there’s no contraindication. Now what’s magic about that age 60, obviously as you know, it’s not magic. It’s more of a statistical, continuous variable algorithm that says around that time, the risk of blood clots goes up.

And so then you’d consider cytoreductive therapy at that point. Now there’s exceptions to that. Many of our young patients are on therapy, but there’s usually some reason for that. Some high-risk feature, wildly uncontrolled blood counts, for example, symptom burden, some other high-risk features. So, it’s a suggestion. It’s a guideline, not an absolute. And then the third part of it is, the what do you do in that time? And that’s the frustrating thing. And I think that’s what Stephanie’s getting to.  

Again, that’s why I said the watch and worry versus watch and wait. Some of it is, how are you feeling outside of this? Some patients take it as a great news. Hey, you have this blood cancer, that’s not good news. But the good news is it’s probably not going to be active for a long time, we can, “just watch it.” But some people, as Stephanie is saying, take it the opposite way. What do you mean I got a blood cancer? I got something lurking in my body. You’re telling me it’s there, you know it’s there. And so what’s up with that? And the concept there is that some of these situations like low-risk ET, we found that if you treat too early, too aggressively, you can actually do harm.  

So, that’s the key. These chemo drugs are not benign as you had me discuss earlier. They have toxicity, side effects, short-term, long-term. So, it’s a risk-benefit thing. If the risk far outweighs the benefit, as in the younger patient with no symptoms, no high-risk features, observation is okay. But at some point, when it turns, that’s the threshold.  

So, really the key is, if we believe these are stem cell blood cancer disorders, we need to be thinking about and designing therapies with minimal to no toxicity. Something that actually modifies the disease early on and something that leads to long-term outcomes. And we don’t have that yet in ET. We’re working on that in PV and myelofibrosis. So, stay tuned for that.

And then finally, let me also add, this is an important point, not everybody gets it. This watch and wait versus watch and worry. So, I’m glad Stephanie brought that up because it’s not always good news, uniformly, when you tell someone, good news is you don’t have to do anything bad news, there’s something there. 

Increased MPN Symptoms | What Does It Mean for Patients?

Increased MPN Symptoms | What Does It Mean for Patients? from Patient Empowerment Network on Vimeo.

What might an increase in myeloproliferative neoplasm (MPN) symptoms indicate? MPN specialist Dr. Naveen Pemmaraju discusses possible reasons for an increase in symptoms and shares advice for seeking care when experiencing common issues. 

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

 

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Understanding and Managing Common MPN Symptoms and Side Effects

Understanding and Managing Common MPN Symptoms and Side Effects


Transcript:

Katherine Banwell:

What might an increase in symptoms mean? Does it mean that the disease is progressing or that maybe it’s time to change therapies?   

Dr. Pemmaraju:

Yeah, possibly. So, with all this objective evidence, there are different buckets of disease progression. And some of them are objective and obvious, rising spleen, increasing blasts, or leukemia cells in the peripheral blood. The start of transfusion dependency for either anemia or platelets that weren’t there before. Sometimes, there are obvious things that you can point to, but there are a couple of scenarios where it’s not as obvious. You just named one. One is increasing symptom burden profile. You see, sometimes you have to think about, is it the sequela of the treatment itself or is it disease progression?  

I’ll give an example. If you start on an Interferon product and the dose is too high, you may be feeling not so great from the interferon. But maybe in that case, a simple dose reduction was the answer, because then you’re still getting the anti-disease activity, less side effects and all that. So, I’ll answer your question by saying possibly, but it can’t be the whole story. So, increasing symptoms is a harbinger, it’s a red flag.

In the clinic, it means pause. Workup, is this a subject of the treatment itself? Is it because the disease is progressing? Do we need to do a restaging and workup, whether that means a bone marrow biopsy, whatever that means? Or again, let’s put that other in there. What about the other comorbidities? Do you have class one heart failure, that’s now class three and you’re retaining fluid? And that’s why you’re short of breath and you actually need an echo and a cardiologist and an evaluation of your diuresis. So, I think that’s important, but the key is don’t blow it off, right? So, increasing symptom in MPN is telling you something isn’t right, and we need to check it out.   

Katherine Banwell:

Right, and for the patient, tell your healthcare team about it.  

Dr. Pemmaraju:

Communicate always. I think what we see is people are so proper and so compassionate and so kind and collegial, and that’s beautiful. But actually in the MPNs and all these rare blood cancers where so little is known and so little is obvious, communication is the key. 

Expert Advice | Strategies for Managing MPN-Related Fatigue

Expert Advice | Strategies for Managing MPN-Related Fatigue from Patient Empowerment Network on Vimeo.

Fatigue related to myeloproliferative neoplasms (MPNs) can be overwhelming and may have an impact on other parts of your life. So, what can be done about it? MPN specialist Dr. Naveen Pemmaraju shares advice for understanding and managing this common symptom, including lifestyle choices that may be beneficial. 

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

 

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Understanding and Managing Common MPN Symptoms and Side Effects


Transcript:

Katherine Banwell:

Well, it’s obvious that there’s some symptom overlap along with this.  And so I’m wondering what the strategies are for managing these. Let’s start with fatigue first.  

Dr. Pemmaraju:

Let’s do that.  

Katherine Banwell:

How do you manage that?  

Dr. Pemmaraju:

This is one of the tougher parts of what we do. I’m glad you’re pinning me down to say it, because really this is the majority of what we need to be talking about in the clinic. I’m going to just be honest, you know, with all the scientific breakthroughs and everything, some of these are limited. The fatigue, this is some of the strategies I use and some of the experts in the field. I think one is managing the underlying disease. So, as you mentioned, if you have high-risk, intermediate to high-risk myelofibrosis, one of the great findings of our field is the JAK inhibitor class generally helps to improve symptom burden.  

So, that is the splenomegaly, the fatigue, the pruritus. Maybe not so much the itching, but some of these other things. So, I think treating the underlying disease, that’s okay. Number two is many clinics, onc centers around the country are starting to open up a supportive care or fatigue center clinic. So, I am referring several of my patients there, we’re talking about diet, nutrition, exercise. We used to never talk about these things. Ruben Mesa has found that doing yoga and meditation can genuinely actually help the pathobiology to reduce the cytokine storm and improve the fatigue and quality of life. 

Dr. Angela Fleischman, our colleague at UC Irvine, has done work suggesting that possibly an antioxidant diet such as the Mediterranean diet can help the overall general fatigue, well-being, wellness. And then of course I mentioned earlier, but I’ll mention here too, sometimes fatigue is outside of the MPN. Have you had your TSH or thyroid checked? What about your vitamin D levels? How are you doing on these PCP general checks? Things that may be contributing to the life and the happiness.

And finally, let me make a plug for mental health. I don’t know how much we were emphasizing before the COVID pandemic, but after, the last three or four years have been tough. Healthcare providers, caregivers, patients themselves, mental health checkup, that can also be contributing to fatigue, not getting out of bed, in addition to the organic medical problems. So, let me advocate a multifactorial approach, scientifically summed up as treating what you can with the underlying MPN, fine, treating the side effects and symptoms of the MPN, as you said. 

And then, other, which can be a huge bucket, particularly as we get older, to not forget about that. Again, checking the thyroid level. And then when you’re on these different treatments, you can personalize it. Interferon, obviously, has its own separate set of side effects and then of course the other agents. So, I think that may be the best way to approach it. Maybe a three-bucket approach. The MPN itself, and then the treatment itself, and then the other, something like that.  

Katherine Banwell:

And as you’ve mentioned, it’s all going to be personalized and individualized.  

Dr. Pemmaraju:

Hugely.   

Katherine Banwell:

Right, because what’s going to work for one person is not necessarily going to work for another.  

Dr. Pemmaraju:

Hear, hear, well said to that. You know, you think you make a great diagnosis in the clinic, someone’s having fatigue, they’re on therapy for your MPN. You check the TSH, it’s wildly abnormal. Okay, you refer them to endocrine. Six months later, the thyroid level is completely normal now on thyroid medicine. And yet, the fatigue, brain fog, everything is still not clear.  

The MPN is under good control. What gives? That’s the difficult part of these diseases. So, I really love what you said about the personalization and to keep looking and keep trying.