Thriving With an MPN | Managing Symptoms and Treatment Side Effects from Patient Empowerment Network on Vimeo.
In this webinar, MPN specialist Dr. Naveen Pemmaraju, discusses strategies for managing symptoms and treatment side effects for people living with essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). Dr. Pemmaraju also shares advice for communicating with your healthcare team and provides an update on the latest MPN treatment and research.
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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Transcript:
Katherine Banwell:
Hello and welcome. I’m your host, Katherine Banwell. Today’s program is a continuation of our Thrive Series and we’re going to discuss coping with MPN symptoms and managing treatment side effects. 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.
Let’s meet our guest today. Joining me is Dr. Naveen Pemmaraju. Dr. Pemmaraju, welcome. Would you please introduce yourself?
Dr. Pemmaraju:
Oh, thank you, Katherine and team. Just an honor to be here.
I’m Naveen Pemmaraju, a professor of leukemia at MD Anderson Cancer Center in Houston. And I also serve as one of our executive directors for the MD Anderson Cancer Network, and I specialize in MPNs and rare leukemia. So, happy to join you once again, Katherine.
Katherine Banwell:
Thank you so much for being with us today, taking time out of your schedule. Well, 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 that 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.
Katherine Banwell:
All right, well, thank you for that. As we get into the discussion, Dr. Pemmaraju, it’s important to note that some of the issues we’ll be talking about today are symptoms of the MPN, and others may be treatment-related side effects. So, let’s start with side effects. What are the most common issues associated with the main MPN treatment classes? Let’s start with JAK inhibitors.
Dr. Pemmaraju:
Oh, very nice. Yeah, that’s exactly the way I think about it too. So, with our JAK inhibitors, we now have 10 years since the approval of the ruxolitinib, the first in class. And now we have two more approved agents which are known as fedratinib (Inrebic) and pacritinib (Vonjo), and hopefully a fourth agent, momelotinib, which is under regulatory review at this time.
[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.]
So, we have a whole class of drugs. They have some similarities and then some differences, but in general, the JAK inhibitor class are well-tolerated drugs, but each of them has some side effects.
I’d like to go through them just as a top-line overview. It’s very important. Number one for the ruxolitinib agent, the one that’s been around longest. This one is usually well-tolerated as we said, but you do have to look out for a few things. Non-melanoma skin cancers can be increased in some of our patients, so the importance of dermatology and skin evaluations. Some infections such as viral herpes, zoster, and shingles, so we need to be aware of that. And then weight gain, weight gain is something that we’re seeing more over time as we appreciate the drug, particularly as we move it into earlier lines of therapy, such as p.- vera.
As I look at the other agents, the fedratinib already carries an FDA black box warning for an encephalopathy syndrome, thought to be Wernicke’s encephalopathy, which can affect the brain. But really an encephalopathy syndrome, which means we have to check thiamine levels and replace them and be aware of that. That’s vitamin B1 and also GI side effects with that agent. And then finally, the pacritinib agent has a few toxicity and side effects.
Again, all these are on the package label insert, well-known. Some GI side effects, particularly in the first few months, including diarrhea, and we need to watch out for bleeding and these kinds of effects, especially in the opening days and weeks of the agent. So, again, JAK inhibitors, well-tolerated class, oral medicines, but can have some notable side effects that we have to follow together in the clinic.
Katherine Banwell:
What about interferon? What are some common side effects?
Dr. Pemmaraju:
Yeah, great. So, the interferon class, which actually now is a class of drugs. We started out as let’s call it the regular Interferon, which was multiple times a week dosing. Then the Pegylated Interferon, which went down to once a week. And then now we have the ropeginterferon (Besremi), which is the recently approved agent in p. vera, which is every two weeks spaced out to every month.
So, as you said, in this class of drugs, what’s old is new again. These drugs have actually been around longer than the JAK inhibitors, interestingly. You do have to be mindful. These are a very serious set of drugs. We usually set aside a good amount of time to talk about the side effects, and they are many historically.
The main ones include psychiatric neurological side effects. So, it can cause a depressed mood, change in the mood, even depression. Hugely important, so everyone needs to be aware of that, including the caregivers. It can cause autoimmune side effects, so such as thyroid, liver, these type of side effects. And then finally, of course, any of these Interferons can cause a flu-like profile, you know, not feeling well, particularly in the beginning days.
So, we usually try to mitigate it with lots of education to the patient, the caregiver, remind all members of the team. If you can, maybe even start at a low dose and escalate up, which is what we’re trying to do in the clinic. And then really close monitoring for stuff that you can monitor, the thyroid, the liver, the mental side effects, as we said. Usually most of our patients over time, most of them do get used to the drug. So, there is some kind of an immune component to it, but you can have side effects at any time.
I would say also, Katherine, that these later forms of the Interferon continue to improve. And so we’re seeing either less and less side effects or at least better managed, better tolerated, more understanding of these. So, a great class of drugs. And I should also say that our colleagues around the world are starting to combine the two classes of drugs for patients with myelofibrosis. And so we need to be paying attention to those combinatorial approaches.
Katherine Banwell:
What about hydrea?
Dr. Pemmaraju:
Yeah, right. Yeah, so hydroxyurea, we also have to mention that.
One of the workhorse medicines of our field. We use it in all the MPNs.
Again, an older class of drugs such as the Interferons that have been around prior to the JAK inhibitors. Used in a variety of diseases, both benign and malignant, used in sickle cell anemia. Historically has been used in both blood and solid tumor cancers, but we use it very commonly in MPNs. Almost all of our viewers are familiar. Hydroxyurea is not a benign drug. It is a chemotherapeutic agent. You know, you have to handle it with care.
And so it’s got a few side effects. It can cause some fatigue in some patients. One of the more notable classical side effects is an ulcer formation, either in the mouth area or in the lower extremities, such is in the feet, so, you know, grossly visible. It can cause some fever and not feeling well in some patients. I will say again, a lot of these drugs are generally well tolerated. Most of our patients are 60, 70, 80, and older, but you can certainly have those side effects. A lot of these drugs, Katherine, can affect the skin.
I did mention that earlier. So, ruxolitinib, even the interferons, hydrea, they can all cause skin lesions, maybe some of them associated with non-melanoma skin cancer, such as squamous cell and basal cell. So, one amazing part of the practice has been close association with our dermatology colleagues, not something I would have expected 10, 15 years ago. And that’s been a helpful part of the practice.
So, I think it’s a point where I can emphasize that, in addition to having us as the MPN or blood cancer team, Katherine, the pandemic has reminded us the importance of primary care team as well. So, it’s really two teams, someone checking the cholesterol, cancer screenings, skin checkups, mammogram, PSAs. And then in coordination with your MPN team and then everyone working together, so colonoscopies, et cetera. So, just a plug there, especially the last three, four years where people have gotten behind to make sure that we’re keeping up with that part of the deal as well.
Katherine Banwell:
With all the testing, yeah.
Dr. Pemmaraju:
Exactly, right.
Katherine Banwell:
You mentioned a couple of treatment side effects and how they’re managed, but in general, across the board, are treatment side effects managed in the same way, in similar ways?
Dr. Pemmaraju:
Now, that’s a great question. So, here I’ve given you this nice list, kind of academic version of the list, but boy, no, right. And all my patients and everyone out there knows that there’s some varied practices. You know, the varied practices are not only, as you say, across the country and across the world, but also even in our own clinics, patient to patient. The MPNs have humbled and taught us that one person’s MPN can be starkly different from the next, so on and so forth.
So, I’m not just talking about the difference between PV, ET, myelofibrosis, and systemic mastocytosis. I’m talking about one person’s MF is completely different than the other. I think there are a couple of things I didn’t mention. So, pruritus, or itching is one of the great symptoms really. It’s not a side effect usually, but it’s a symptom of the MPN. There are some ways to treat that in the clinic.
Fatigue really has no great way to treat it. Usually when you introduce one of the JAK inhibitors that can improve. On the side effects side, as we were mentioning, a lot of these are unsatisfying things. The flu-like symptoms of the interferon, the weight gain of the JAK inhibitor. So, I think what you’re saying is so correct, and let me admit it, I’m going to be the first to admit it, there’s not really a good standard playbook.
But on the other hand, I think personalization. As we’ve always said, in our rare disease space, if you have a disease, it’s not rare to you. It’s what you have, it’s what your spouse is dealing with, your loved one, your mother with you. And so, I would advocate here that there’s a personalized playbook there. I would say that there are three guiding principles though. One is when you have side effects of a medicine, the first thing to do is let your healthcare provider team know. I know that sounds obvious, but here I am in the clinic and sometimes we don’t find out until later.
And so some of that is because the patient says to themselves, let’s tough it out. Or they may not know, or they may not be able to, or it may not be easy to communicate with our healthcare teams. Two is when you’re evaluating, every patient’s case is different. This is not specific advice, as you said, at the top of the hour here. But in a general sense, you really need to evaluate if the side effect is peculiar or particular to just that patient case, so idiosyncratic, unpredictable, notable.
Or, is it a general expected sort of something that you thought could already happen and then go with it from there? And then finally, the concept of dose interruptions, dose reductions, treatment holidays, something very important. So, basically a lot of different ways you can go, but no standard or uniform playbook in our MPN field, as you and the team well knows.
Katherine Banwell:
Thank you for that Dr. Pemmaraju. I’d like to move on to common MPN symptoms now. Let’s start with myelofibrosis. What are the symptoms associated with this particular MPN?
Dr. Pemmaraju:
Excellent question. So, for the myelofibrosis, generally thought to be our most advanced of the MPNs, can be low risk, intermediate to high risk. We’ll focus our comments here on intermediate to high risk, the more advanced MF. This is important because not only what I’m going to tell you is sort of a subjective list of symptoms, but because of the work of my great friend, Ruben Mesa, who pioneered the MPN symptom burden, we’ve actually been able to, as he and I say, quantify the unquantifiable.
So, take subjective information and turn it into objective. For example, we know that among the three MPNs, PV, ET, and MF, that fatigue is by far the most common symptom that our patients report. It’s a fatigue that’s more than the general feeling tired at the end of the day. It’s sometimes a wiped-out fatigue. Some of our patients will have pruritus or itching. Many of our patients will have early satiety, which means getting full too early because either the spleen is too big, decreasing the appetite. Bone pain and neuropathy can happen in our MF patients. Brain fog and decreased concentration, huge issue among a lot of our patients.
And finally, because of the low blood counts, if a myelofibrosis patient is anemic, they can have those issues. So, fatigue, shortness of breath, even chest pain and palpitations. If the platelets are too low, or too high for that matter, bleeding or clotting.
So, the problem with myelofibrosis, it ranges the gamut from the low-risk patients, who can be treated maybe even as a PV or ET observation or not as advanced treatment paradigm, all the way to intermediate high risk where patients are cachectic, losing weight, not feeling well, drenching night sweats. And all of these can be captured on not only the scoring systems but also the symptom burden scales. And to be honest with you, this is the majority of what our patients are feeling outside of the blood counts and outside of the objective information. So much so to the point, Katherine, where a patient can present with these symptoms solely, without ever having a blood count or a bone marrow or anything, and then it leads to the work of it.
Katherine Banwell:
Oh, wow. Wow, fascinating. What about symptoms for polycythemia vera?
Dr. Pemmaraju:
Yeah, so this is a great theme that you’ve got going here, which is know your body. If you know your body, then you’re able to tell what’s abnormal or normal. p. vera can be a bit more subtle.
Oftentimes patients with p. vera can have a normal life expectancy and the longer term series in Europe show that it’s basically about the same life expectancy as the general population or slightly lower. But that doesn’t tell the whole story. Patients with p. vera can have an unbelievable symptom burden, either from the hyperviscosity of the hematocrit, the blood level being too high or the cytokine storm, that I mentioned, that makes people feel not well. So fatigue, brain fog, feelings of sluggishness, feeling too full, those are common in p. vera.
The treatments are aimed at trying to make that better. So, phlebotomy to bring the hematocrit down below 45 can make you feel a little bit lighter, a little bit better, decrease the brain fog. If you’re using either the standard treatments of hydrea or Interferon, and then, of course, the baby aspirin to prevent clots, heart attacks, stroke. The newer agents in p. vera include the ropeginterferon that we mentioned earlier, clinical trials, such as the PTG-300 that I’m a part of, that try to really keep the blood levels normal all the time.
And so hopefully help to improve the quality of life, decrease the chance of having a clot, and also hopefully try to make patients feel better from these aspects.
Katherine Banwell:
What about essential thrombocythemia or ET?
Dr. Pemmaraju:
ET, again, just like PV, you can have a lot of patients who are either incidentally diagnosed or not too much of a symptom burden. But again, here, the blood counts don’t tell the story. You can have “low risk ET” which is defined as less than 60 or no prior blood clots. So, you can be 43 years old, diagnosed with ET, your blood counts aren’t that high, but yet you’re still feeling overwhelming fatigue, itching. You’re seeing flashing things in your eyes called scotomas. You’re having small nerve or vascular issues called erythromelalgias. It’s a very elusive and difficult disease, particularly for our young patients. So, in ET, again, the same set of symptoms can happen. This fatigue, itching, the brain fog, concentration, bleeding, and or clotting.
And so again, the goal of therapy is to mitigate those. If you’re young, a lot of patients are either observed or baby aspirin. If you’re older than 60 or have high risk features, then again, cytoreductive therapy. The other aspect I should mention is you can start out with one of these and it transforms into the other. That’s called clinical or phenotypic shifts. You can start out as an ET, go to PV. You can start out as PV and go to myelofibrosis. You can start out as myelofibrosis and go to acute myeloid leukemia. So, that’s why follow-up, even over years, decades, is important, preferably with an expert team, because you never know when one of these things wants to transform. And then your side effect, or I should say your symptom profile therefore changes with that transformation.
Katherine Banwell:
Well, it’s obvious that there’s some symptom overlap along with this.
Dr. Pemmaraju:
Right.
Katherine Banwell:
And so I’m wondering what the strategies are for managing these. Let’s start with fatigue first.
Dr. Pemmaraju:
Let’s do that.
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