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Transcript:
Katherine Banwell:
Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today’s webinar is a continuation of our Thrive series. And we’re going to discuss how to manage life with an MPN. 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. Raajit Rampal. Dr. Rampal, welcome. Would you please introduce yourself.
Dr. Raajit Rampal:
Hi. Thank you so much for having me. I’m Raajit Rampal from Memorial Sloan Kettering Cancer Center where I focus on myeloproliferative neoplasms.
Katherine Banwell:
Thank you so much for being with us today.
Dr. Raajit Rampal:
My pleasure.
Katherine Banwell:
As we do with each of the webinars in our Thrive series, let’s start with this question. In your experience, what do you think it means to thrive with an MPN?
Dr. Raajit Rampal:
It’s a great question, right. I think taking a step back, when we think about our patients with MPNs, one of the questions I always have for patients are what are your goals. And inevitably and invariably, people want two things. They want to live longer and they want to live better. And so, I think that thinking about thriving with an MPN to me is about how do we minimize the impact of an MPN in someone’s life. And that means a couple of things. One that means how do we deal with symptoms or things that are causing medical problems.
But two, how do we deal with the anxiety of a diagnosis? In many cases in my experience, that can be just as detrimental to somebody’s well-being as the actual physical symptoms of the disease.
Katherine Banwell:
When it comes to choosing therapy for polycythemia vera essential thrombocythemia, or myelofibrosis, it’s important to work with your healthcare team to identify what is going to work best for you. So, to begin, would you define shared decision making and why is this critical to properly managing life with an MPN?
Dr. Raajit Rampal:
Yeah. Shared decision-making, to me, is really about the physician or whoever is on the healthcare team providing the patient all of the information needed to make a good decision. That means what are we trying to do? What is the medication or invention going to accomplish? What are the side effects because there are always side effects.
And what do we think that’s going to do or how is that going to impact the patient’s life? Where things get nuanced is that patients come to us because we have expertise. There are two extremes. One extreme is that the physician says this is the medication you should take. End of discussion. The other extreme though is also not helpful, which is to say to a patient here are five choices. Here are the side effects. You pick one. Our job is to lay out those side effects and the benefits but then, also help guide a decision.
Katherine Banwell:
What are treatment goals and how are they determined?
Dr. Raajit Rampal:
It depends on the disease to a large extent. Now, when we’re dealing with ET and PV, the primary goal of our interventions is to reduce the risk of a clotting event or bleeding event. And that usually involves controlling the blood counts in some cases, not in all patients with ET.
Sometimes aspirin is all we do. Myelofibrosis is a little bit more complicated because it depends on what the problem is. Not all myelofibrosis patients have the same challenges. Some have anemia that needs treatment. Some have a big spleen. Some have symptoms and some have nothing and they just need observation. So, it’s a bigger list with MF patients. But I think the first part of the discussion always is defining what the goal needs to be.
Katherine Banwell:
What factors are considered when choosing therapy for ET, PV, and MF?
Dr. Raajit Rampal:
I think a couple of things. One is what medication we think is going to benefit the patient best. That has to take into account the individual, their willingness to take certain medications, for example, pills versus interferon injection. Some people have an aversion to self-injection, which we have to take that into account. What are the other medical conditions that the patient is dealing with?
And the reality is, in some cases, it’s cost because these medications, depending on a patient’s insurance, can have quite a different spread in terms of cost. Unfortunately, that is something we have to take into account.
Katherine Banwell:
Let’s talk about what sort of tests should be done following an MPN diagnosis. Can you tell me about those?
Dr. Raajit Rampal:
Yeah. Fundamental to the MPN itself, the things that we really want to know is, in most cases, a bone marrow examination is needed because that will tell us really what the disease is that we’re dealing with. It will tell us about the genetics. I strongly believe we have to be comprehensive in our genetic assessments because that does prognosticate and sometimes gives us an opportunity in terms of treatment. Chromosomal analysis. These are the basic bread and butter hematology tests we want to do from the bone marrow to really understand what the patient’s disease is.
Beyond that, I think that particularly in patients with PV and ET, it’s important that we partner with their primary care physicians to make sure that they’ve had, for example, testing for diabetes, a recent lipid profile, any cardiovascular tests, particularly measurements of blood pressure because these things are all important in terms of an ET or PV patient’s risk of having a blood clot. So, there are, again, things that are within hematology realm but then, there are other general health things that become really important in somebody who is diagnosed with PV or ET.
Katherine Banwell:
How often should lab tests of blood work be done?
Dr. Raajit Rampal:
It really depends on the patient. For some patients with PV, for example, they need to have their blood checked every three weeks because they’re having frequent phlebotomies. Whereas some patients with ET could probably go forward to six months between blood tests.
So, it depends on the individual.
Katherine Banwell:
How can results of biomarker testing affect treatment choices for patients with MPNs?
Dr. Raajit Rampal:
question. The genetics are becoming increasingly important in our treatment decisions. So, let’s take a simple example, which is patients with ET. Calreticulin and JAK2 and MPL are the three most common mutations that we see. But they have very different invocation. So, somebody could have a calreticulin-mutated ET and based on them having that calreticulin mutation and no other factors like no history of clotting, that patient may never need to go on a medication aside from aspirin. And even early on, it’s debatable whether or not some of these patients really need aspirin at all.
Whereas somebody who had a JAK-2 mutant ET, our guidelines and data suggests that that person, once they reach a certain age, should probably be on medication. So, that’s kind of perhaps one of our more clearcut examples of a genetic biomarker telling us how to approach treatment.
And then, it gets more nuanced from that and more exciting and interesting in the sense that there are mutations, for example, that occur in myelofibrosis and in patients whose disease is progressing towards leukemia, such as IDH mutations. And these are things that are now targetable with FDA-approved drugs.
And there are now clinical trials combining JAK inhibitors and IDH inhibitors for patients who have more advanced disease who have these IDH mutations. So, you go from on one end, these genomic markers being of prognostic significance and now, on the other hand, we’re getting to a point where, in some cases, they might tell us how to best treat a patient.
Katherine Banwell:
Dr. Rampal, should all patients diagnosed with MPN’s undergo molecular testing?
Dr. Raajit Rampal:
I strongly believe that. I think that we’ve learned so much that these tests have prognostic value.
And in some cases, it may suggest a slightly different diagnosis. I definitely think that should be the case.
Katherine Banwell:
What should patients be asking once they have the results?
Dr. Raajit Rampal:
What does it mean? That’s the most basic and fundamental question. It’s one thing to get a list of mutations. But the real bread and butter question is what does this mean to the disease and my prognosis and my treatment? Those are the key questions.
Katherine Banwell:
So, what are the types of treatments available for MPNs? And let’s start with myelofibrosis or MF.
Dr. Raajit Rampal:
If we had had this discussion five years ago, it would be pretty simple, and it would take a minute or two. And that’s completely changing and that’s amazing, and it’s good for all of our patients.
Right now, for patients with MF, it depends on what the issue is. If the issue is symptoms or spleen, JAK inhibitors are our first line of therapy. Three approved JAK inhibitors are currently available, two on the first side ruxolitinib (Jakafi) and fedratinib (Inrebic). And pacritinib (Vonjo) can be used for patients with really low platelet counts.
There is a fourth JAK inhibitor that we expect to be, hopefully, approved in June of this year, momelotinib. So, the landscape is about to complete broaden in terms of just JAK inhibitors.
But beyond the JAK inhibitors themselves, there are a number of late stage clinical trials that are combining JAK inhibitors with agents that work through a different mechanism that don’t work through inhibition of the JAK pathway. So far, these drugs have all shown promise in early phase trials. Now, the definitive Phase III trials are being done. We have to wait and see what the data tells us. But if these are positive trials, this could completely alter the landscape of MPN.
Katherine Banwell:
There’s also transplants available, right?
Dr. Raajit Rampal:
Correct. Transplants for more advanced patients, which comes with some major risks. And so, that has to be thought of very carefully in terms of the risks and benefit. But it is a potentially curative strategy.
Katherine Banwell:
Let’s turn to polycythemia vera or PV. What types of treatments are available?
Dr. Raajit Rampal:
It’s really quite a range. So, there are things like phlebotomy and aspirin, which has been the mainstay of therapy for many years. There are drugs like hydroxyurea (Hydrea), interferons, JAK inhibitors. So, ruxolitinib is approved in certain settings for treating polycythemia vera. So, the landscape is broad. There are a lot of questions going on right now with polycythemia vera with regards to how it should best be treated. Is the mainstay of phlebotomy and aspirin really what we should be doing or should we be giving patients treatment earlier on.
And there is some data to suggest that. There is this drug called ropeginterferon (Besremi) that’s FDA-approved for polycythemia, which was compared in the study to phlebotomy and aspirin.
And at least the data suggests that there may be better control of the disease and less progression possibly, and it’s a small number of patients, by treating patients earlier. Whereas we would have just given phlebotomy and aspirin. So, it’s something to consider. There are drugs in clinical trials as well that look promising one of which is called rusfertide, which actually works by changing the way iron is used by the body.
Iron is a key component to hemoglobin and it is, of course, a key component to polycythemia in the sense that we phlebotomize patients to make them iron deficient and that’s how we control the disease. But this is a pharmacological way to do that. So, that drug is now in Phase III trials. So, that may also alter the landscape of treatment of PV in the near future.
Katherine Banwell:
Finally, how is essential thrombocythemia treated?
Dr. Raajit Rampal:
So, in some cases, with absolutely nothing as we had talked about a moment ago. There is some thought that in really, really low-risk patients. Maybe you don’t need to do anything except observe them. Whereas most patients are on an aspirin. And beyond that, we have drugs like interferon, pegylated interferon, and hydroxyurea and anagrelide, all of which can be utilized. It’s not entirely clear if there is one distinct first line treatment that is the best but these drugs are all active. JAK inhibitors have been studied in this setting. And to date, the data hasn’t led to their approval but, certainly, people have studied it.
Katherine Banwell:
Dr. Rampal, how can you tell if a treatment is effective? Are there signs that you look for?
Dr. Raajit Rampal:
Well, I think it’s a couple of things.
One, are we meeting the treatment goals in terms of are we controlling blood counts with ET or PV? That’s one of the first principles in management. And with regards to MF, the same thing. Are patients’ symptoms being controlled? Is the spleen being adequately controlled? And then, there’s the symptom burden because just because the blood counts are being controlled, patients may still have symptoms, in which case, they are not being adequately treated. And then, we have to do our best to try to find a treatment strategy that does control their blood counts but also does control their symptoms.
So, there is the blood count perspective but there is the symptom perspective as well.
Katherine Banwell:
How do you know when it’s time to change treatments?
Dr. Raajit Rampal:
Well, I think really two things. One is if we aren’t meeting our goals like we just talked about. But the other aspect of that is if we are incurring toxicities that are just not tolerable to the patient and that’s a reason to change therapy always.
Katherine Banwell:
Many patients, of course, worry about disease progression. Are there key predictors or tests for progression that patients should know about?
Dr. Raajit Rampal:
This is a key area of investigation currently. I think one of the things that patients say to us so often when we meet them is what’s going to happen to me. And right now, we don’t have great prediction tools. We can say on a population level well, there is X percent of chance of progression at 15 years. That’s useful if you’re talking about a population. That’s not really useful if you’re talking to an individual. Because if I say to somebody there’s a 20 percent chance of your disease progressing to leukemia, it doesn’t really make a difference. That’s a meaningless statement because if you’re in the 20 percent who progress, it’s not a relevant statistic anymore.
It’s sort of a binary thing. We’ve got to do better at developing this. This is something that the MPN Research Foundation is really heavily invested in in trying to identify predictive biomarkers.
If we can do that, then perhaps what we can do is say to a patient this is really what we think your actual risk is. And then, the next step is asking the question if we intervene early, can we prevent that progression from occurring. So, that’s where I think we need to go. We aren’t there yet.
Katherine Banwell:
What signs or symptoms do you look for that may indicate that the disease is progressing?
Dr. Raajit Rampal:
The blood counts are often the canary in the coal mine regardless of the disease. They can tell us if ET or PV is progressing into MF or whether MF is progressing to more of a