Navigating the Currents: Interferons in the Treatment of Polycythemia Vera

Thank you, Farma Ascensia, for supporting this episode of Bloodstream. Hello and welcome to the Bloodstream podcast, a show serving the greater bleeding disorders community brought to you by, believe limited and bloodstream media. I am your patient advocate and host Patrick James Lynch. And I am your healthcare advocate, non-profit nerd and your other host Amy Bord. Reminding you to please speak to a healthcare professional before making any treatment decision. That remains a great idea. On today's show, we navigate the intricate world of polycythemia vera or PV treatment. Yes. Focusing on the role and implications of interferon therapy with Dr. Anthony M. Hunter. Yes. It's a great interview coming up in just a little bit. Welcome to Bloodstream. Hey listeners, thank you for joining us today. If you like what you hear, please share this episode on social media and subscribe to Bloodstream wherever you get your thanks. You are so many good ideas. Talk to treatment health professionals about treatment, subscribe to all the things. 100%. I just want to know that I have the good ideas. Amy is the idea engine of this show. This show that we are very pleased to be able to bring to you today made possible by Pharma Ascensia. So we're we're going to navigate this intricate world of PV. I know. It's a pop-up episode. It is a pop-up. That's my favorite. I know. Patrick loves a pop-up. I live for this. I live for this. We don't plan some of these episodes. We do so many and then once in a while we get to do one that's unscheduled, I get excited. Oh my god. Keith and Amy have different emotional experiences. But I get very excited. Thank you for giving me the opportunity to celebrate this. But what I like about this these episodes is they give us the chance to like hunker in on a particular topic. Something we wouldn't otherwise get to spend as much time on. And in this case, it's interferon therapy. Why are we talking about interferon therapy? What is it? We're going to unravel all of that. We're going to talk to an expert. That's what today's episode's all about. Ready Amy? I guess it's the 100%. I would just like to mention this interview is great. Dr. Hunter is just great. But I also got to tell him that this treatment name, interferon, actually sounds like it's out of like a sci-fi novel. It does. Well, I was going to ask you what does he say to that. But we will wait because I don't want to step on the response. We will just tease that. I'm glad you asked those kind of questions though. For those who may be wondering what polycythemia vera even is before we go too far with treatment option talk, it is a type of blood cancer though. It's not always talked about that way. It is a type of blood cancer that originates in the bone marrow. The soft tissue inside bones where blood cells are produced. And in PV, the bone marrow produces an excessive amount of red blood cells. And sometimes also an increased number of white blood cells and platelets. And this overproduction leads to a thickening of the blood which can cause a range of issues including blood clots that lead to serious complications like strokes or heart attacks. PV can also progress to mylofibrosis or acute myloid leukemia. People with PV might experience symptoms such as headaches, dizziness, itchiness, especially after hot shower and a reddening of the skin. However, some individuals might not have noticeable symptoms. That's part of what makes this thing kind of challenging. And that's especially true in the early stages of the disease. PV is generally a slow growing cancer. It is generally a slow growing cancer that can be managed for many years with proper treatment. So Amy, let's come back to this interferon thing now that we've laid a little bit of groundwork here. Why treat PV with interferons? What's this interferon thing we're going to hear Dr. Hunter talk about? Yeah, he will explain it much better than I do. Shocker. You are not an expert in polycythemia vera. No, I'm not. But I will say it is I think this is fascinating because it is a treatment that I think is it is necessary to advocate for as a patient. And so it's just one of those things that education is really important. Interferrons are used to treat PV primarily because they have the ability to slow down that production of blood cells in the bone marrow issue we're talking about. Yep. This is thought to help with controlling the blood counts and having an effect on symptoms. And Dr. Hunter was just lovely. And he just, you know, he he he talked to me as you all know. I asked questions like, please explain this to me like I'm in third grade. And he did. But that's that's what I want to hear. By the way, speaking of third grade, do you know that I only just put together that interferons interfere with that which leads to over production of blood cells? Yeah, Dr. Hunter said that. I didn't get it. I didn't you didn't put that together. I did not put that together. That makes me feel a lot better because this is embarrassing for us. And if we were smarter Keith, we should probably cut this part. But we have been working on the PV pod stories from the marrow for quite a while. Right. You would think we've been working on that for I'll say far too long to not have put together interferon interfere with the overproduct. But we've done it right here with you today. We have learned about what interferons do and why they're called what they're called. And I think now we're ready for Dr. Hunter to teach us more. Amy, give us the high level. What's his background before we jump into the conversation? He's a cool dude. Oh, okay. That's it. That's his bio. Dr. Hunter is a cool dude. No, no, no. He's the assistant professor of hematology and medical oncology at Emory. Listeners, today we will be exploring the role of interferons in the treatment of polycythemia vera. We'll also discover or explore rather the efficacy benefits and potential side effects of this treatment momentality and discuss its evolution over the years all with our guest, Dr. Tony Hunter, who will address common barriers, misconceptions, and the futures of interferon therapy in PV. Dr. Tony Hunter, welcome to Bloodstream. Thanks for having. Thanks for being here. I should say Dr. Tony. Absolutely. Appreciate the invitation to be here with you guys. So give us a rundown. Briefly kind of explain what interferons are and how they work in the context of treating PV. Yeah, absolutely. So interferons are something we know about for a long time and they're a type of protein called the cytokine, so sort of a signal for the immune system, so to speak. And so we've known about these for quite some time, specifically relating to their effect on infections, especially viral infections. And but we have now sort of applied them for actually decades now for use in a number of diseases, including MPM diseases like PV. And so in reality, we don't fully understand how they work in place at the immune era. And anyone who does, that would be fantastic. But they're very complex. And so we don't fully understand entirely how they work, but we know a number of different things about them. So certainly they have effects on the immune system. And they sort of modulate the immune system. We think that can have effect on the immune system, helping sort of recognize these abnormal cells in the bone marrow. And we also know that they have direct effects on the bone marrow and the blood cells themselves. So they are, we call cytotoxic, they sort of lower the blood counts. It's of course their goal in PV is to help lower the blood counts. They have a number of effects directly on stem cells in the bone marrow. And then we think that helps sort of target these, we call stem cells, sort of the cells that, you know, originating this disease in the first place in the bone marrow. And maybe part of the reason we see some of the benefits that we do that we'll talk about with Asians like this. Cool. How effective are they in the treatment of PV? They can be effective. And so there's been a number of studies over really decades now looking at, you know, the use of interferons and PV. And a couple more recently that have been reported. And some of that, you know, what is effective depends on what you're defining that as in different studies and things. But if you want to go, you know, kind of talk more broadly about, you know, are they good at controlling the blood counts they are? And we see that, you know, in a number of studies somewhere around 70 to 85% of patients will get good sort of control of their blood counts and PV. That means hopefully not needing things like phlebotomy. And the key one that we really highlight with within our fear on type agents is that they have the, you know, we think the potential to really help this disease long term. And one way that we look at that is, you know, PV patients generally all have a mutation in a gene called Jack 2. And we can monitor basically the level or we call a leal burden of that mutation at diagnosis and over time. And what we can see is that a sizable subset of patients on interferons that sort of a leal burden or that percentage of Jack 2, we will actually see decrease over time. Sometimes the very low levels are even becoming undetectable when a subset of patients as well after several years of interferon therapy. Interesting. You mentioned subset of patients. Are there, is there a specific group of subset folks that might benefit the most from this therapy? Yeah. You know, in general, we think interferons can definitely help sort of patients across this section with PV. I tend to use them a little bit more in younger patients, especially those less than 60. But generally, we think sort of across the board, most, you know, patients with PV, you know, have the potential is certainly to benefit from, from interferon agents. What are the side effects? Yeah. So number of side effects, and this is always a big discussion with the interferon. Yeah. And you know, so there's a couple different groups out of sort of side effects that we'll talk about. So the first is the typical sort of inner-fieron side effects are flu-like symptoms as people sort of describe them. So inner-fierons, right, in normal and RMEU system are sort of a way that our body helps respond to infections like viral infections in the flu. And so those flu-like symptoms, you get fatigue, body aches, headaches, sometimes fever, those sorts of things, really come from interferon, you know, in your immune system sort of fighting that virus off. And so sometimes we can see those sort of side effects in patients on interferon. That's something that, you know, I think we see a less of now, certainly than we used to. So we've had different formulations, more long-acting formulations of interferon over time, which helps to negate some of those symptoms. You're not having to use the treatment is off and now, which is helpful. Okay. And I think there's also a big factor in the dose in those sort of symptoms. And so my Go always within. interferons as I start low and go slow so to speak, right? So we started a lower dose and sort of slowly tight trade up that dose, only as high as I need to get to sort of control the blood counts like we want. And so hopefully, what's to maintain in a little bit lower dose is that can help minimize some of those side effects for people. But not uncommon, you know, 24, 48 hours after an injection. This is an injectionable drugs. And may notice a little bit more fatigue or headaches and things like that. So that's sort of one group of side effects we see. And certainly the goal of these medications is to lower the blood counts. So sometimes we can do that too much. And we may be trying to lower the red blood cells in a patient with PV, but the lower the white blood cells a little too much. And that can make us adjust the dose, for example. And but that's a big key of how we adjust the dose, is sort of based on how those blood counts are doing. And we can see not uncommonly some, usually mild elevation in the liver test or the liver enzymes. And it doesn't equate to long-term damage in the liver, but can see that fairly commonly. And so we'll watch that. And then there's a couple of two, I would say, sort of bigger groups of things that we worry about. So in her fear on agents have a black box warning for basically depression or sort of psychiatric symptoms. And so that is something that I talk to patients a lot about. You can see some anxiety or depressed mood with this. Occasionally in some studies, some reports of suicidal ideation and things like that. So it's something that I can follow my patients about. I worry about this more in patients who have a preexisting history as some sort of mental health condition. I think that's more impactful generally in patients who do. And certainly some patients who have had significant psychiatric conditions and things like that, I may not go for a treatment like in her fear on just for the fear that we may worsen that a little bit. The other sort of group of side effects that are not common, but can be more significant are sort of inflammation-related side effects. Again, we mentioned these treatmentally affect the immune system. And so sometimes we can ramp that immune system up a little bit too much. And that can cause inflammation and irritation in various places. And most common is the thyroid gland. And so that's something we watch through therapy as monitor sort of the thyroid function. That's generally a relatively simple one, but can put require patients to need thyroid hormone replacement long-term in some patients. And occasionally we do see more concerning inflammatory symptoms, bad sort of joint aches and pains, almost like other autoimmune conditions like lupus and things like that. Sometimes trash is related to that. And so that's something that we do need to watch for. And a small subset of patients can get that more significantly. You may have to come off of treatment for that. And so those psychiatric conditions. And then likewise, people with significant history of inflammatory conditions like lupus or inflammatory bowel diseases are ones that I'm a little bit more thoughtful about using interferon agents versus some other alternative agent. Just for the fear that may be worsen a little bit. Yeah. How did these-- this category of side effects, how do they compare with other treatments for PV? Yeah. So I would say that overall, I think the way that I describe interferons is that they do have a little bit more potential for side effects than some of the other drugs that we use. And so obviously some patients with PV don't need to be on a drug. We can do phlebotomy or removing blood, just like donated to the unit of blood basically. And we can use that to lower the blood counts. And so generally not a ton of side effects. Patients may notice some lightheaded dizziness, things like that right after doing that, sort of like donating blood. But generally not a lot of lasting side effects from that. The main alternative agent that gets used by far, in this country as well as worldwide, the most in diseases like PV is hydroxyurea or hydria. That is one that honestly is often a pretty simple medication to take. It's a pill, right? There's definitely potential for side effects like any drugs that we use, obviously. But most patients tolerate hydria quite well. And a relatively low number of patients that truly have to come off for side effects. And so I think that there is at least the potential for a little bit more and sometimes concerning side effects like these inflammatory or psychiatric side effects that we can see. And I think that is a hindrance for some doctors and patients to think about interferon agents. But ones that in reality, I think when you have experience and know how to do these agents, I think you could overcome a lot of that good counseling and knowing what to watch, foreign things like that. And in reality, I think in the long run, the number of patients who truly have to stop the medication for side effects generally starts to be relatively low if you can overcome some of those things. - What are the benefits? What are the efficacy benefits of this? And what are the benefits? - Yeah, so number. So I think obviously in PV our sort of basic goal, right, is to keep that hemoglobin in hematocrit, right? The red blood cells down and we know that 45% is a big threshold that's been well established from some big relatively older clinical trials now. And so if nothing else, that sort of a beer and a minimum right is to try to keep that hemoglobin or specifically the hematocrit less than 45%. And ideally, we try to do that if we're using a drug like interferons without the need for phlebotomy. Now there's a subset of patients, we won't be able to fully control that and we may need to do an occasional phlebotomy in addition to interferons. But usually I would say about 75, 80% of patients, we can control the blood counts quite well and really eliminate that need for phlebotomy, keep that hematocrit where we want to. And again, the big goal for that is to decrease the risk of blood clotting events. And that's how these types of treatments work. And certainly beyond just the red blood cells, we can control the platelets and the white blood cells which are often elevated and PV patients as well, which also especially white blood cell count has an impact on that risk of blood clots. And so obviously try to control that number, but the big long-term goal of that is by controlling those blood count numbers is to decrease the risk of blood clotting events. We don't really know that interferons are any better than hydria, for example, or another drug like Ruxoletnibat at sort of preventing those blood clots long-terms. We know that a lot of our work historically in PV has been to try to decrease that risk of things like blood clots, but we know that probably between 15 and 20% of patients with PV can progress to mylofibrosis, which is in that same NPN disease family, but is more aggressive. Another 3% or so that may progress to acute leukemia. And so historically, we haven't done necessarily a lot to try to prevent that. And we think obviously those are all very important things to work to prevent. And so some evidence now, and even in a randomized trial, that there is some capacity for interferon to do that, there was another large, more retrospective. So sort of a study just looking back at patients that were treated at one of our big centers here in the US, and that was published a couple of years ago that also showed in lower risk PV patients, it seemed to decrease the risk of turning into mylofibrosis with interferons compared to hydria or phlebotomy. And in higher risk patients actually seemed to improve overall survival. So patients living longer with their disease. And so beyond just that, those numbers and trying to control the blood counts, we think we do get more benefit with interferons of lowering that jack two level and ultimately correlating with some of these important long term outcomes that are really important for us to try to shoot for. That's fascinating. In your opinion, or kind of from your chair, I would say what are the barriers to patients getting access to interferons? Is there first hurdle of the physician? Is the physician usually for it? Is it insurance? What is it in terms of access? Yeah, definitely I think physicians tend to be the biggest barrier for this. And so-- A brutal-- I mentioned worldwide and very much so in the US. Hydria is by far the most commonly prescribed drug for diseases like PV. And it's understandable. It's cheap. It's relatively simple to do so and use it's generally well tolerated. But certainly, I think interferons do get underutilized. And I think a lot of that gets back to more remote data, talking about some of these, maybe more concerning side effects and some of the things that can make interferon a bit more challenging. And so I think a lot of physicians don't really use interferon. Certainly, other doctors in the US, that larger academic institutions like myself would treat a lot of MPNs. Most of them use a lot of interferon as do I. But if you look at, of course, the majority of patients are treating more in the general community oncology setting. And most of those doctors use very little interferon. I've given a number of talks and discussions with some of the more community-based oncologists. And the vast majority have no patients in their interferon in their clinic, and occasionally will have one or two. And so I think part of that is probably the biggest barrier as a lot of physicians just don't really use interferons in their practice. And again, I think some of that is a misunderstanding or concerns about some of these effects that we've seen with interferon agents in the past. And I think a lack of knowledge of some of this more emerging data about some of these better long-term impacts of interferon agents over time. P.V., some doctors don't call it cancer. It is. It's a blood cancer. And some doctors still don't even really think of it as such. And I think there's somewhat of a misunderstanding that yes, the majority of P.V. patients do very well, especially in the grand scheme of patients walking into a cancer center. But P.V. does still shorten overall survival compared to the normal population in the US. And there is risk for things like blood clots. The 15 to 20% will be progressed to mylofibrosis at some point in there. So there are other things that we do. And theory want to try to prevent as well to make sure that patients can live as long as-- and as well as they can with this disease. And so I think that's some of the biggest barrier is that that physician, that prescriber level, I think. Patients, I think hit or miss, depending on their opinions about a drug like interferon as well. And you talk about that some more. And the interest in insurance can certainly can be. And these drugs are not necessarily cheap either. And so that can sometimes be a factor. And that can still vary from patient to patient on what sort of. of co-pays and out-of-pocket expenses look like there are grants and programs out there to sort of help cover that. And certainly our pharmacists in my practice do a great job of helping connect patients with that if it's a problem. But certainly not everyone has the resources of a huge cancer center that we do that can help connect to some of those resources as well. Before I ask my next question, I just have to say, interferon sounds like a sci-fi term. You get to say it every day. Congratulations. You picked a phenomenal field. You get to say interferon. Yeah. Exactly. Right. It's a fun name. It was actually the name interferon and comes because these sort of compounds or proteins in the body help the body interfere with viruses. Oh. That's how they got their name decades ago. It sounds. 100% is probably in a sci-fi book. Exactly. Some cool sci-fi novel from the 50s. My next question is my favorite question to ask doctors. You're the hot. Put you on the spot. What is your advice? What's your guidance to some patients that might be listening to this going into their physician? What question should they ask? What research should they bring in all the things? Yeah. I think the biggest thing is that, you know, interferons are perfect. No drug is that we have. But they need to be talked about more. I think. And we have newer formulations that we have more and more emerging data for some other long term benefits, I think. And so that's the biggest thing is to talk about it, I think. Because a lot of time it's just sort of, hey, we're going to start you on hydria. This works well. And it's not really brought up. So I think it is important to recognize that these are treatment option that's out there. Maybe not for everybody. There's maybe not everyone that's going to want to do something like this. Some patients will have some of those contraindications like inflammatory diseases or bad depression and things, which maybe reasons to not think about a drug like this. But it doesn't need to be more part of the conversation, especially, again, I get back to younger patients or patients who are more motivated to really try to impact some of those things, those more concerning, relatively low risk, but still risky things long-term. If you're more motivated to do those sorts of things that interferon is really the drug, these are the drugs you want to be thinking about. That's great. Thank you for your time. Last question for you, good sir. What does the future look like for interferons? What's the research kind of looking like here in the next year or five years? What's the conversation in the community? Absolutely. I think, you know, interferons have evolved over time. That's where I think some of those misconceptions come from. It's from older, short-acting formulations where we're using really high doses multiple times a week. Now we've sequentially developed long-acting formulations and gone from multiple times a week injections to once a week to now every two weeks. That can even be spaced out for their patients to respond. I think to help to add to that, we try to do what's called real-world data. We look at patients that we treat in big centers and try to kind of combine our data and look at how are we doing with things like interferon? Do we see it truly holding up as maybe a better impact on somebody's long-term outcomes? We've had some data to show that already in the last couple years, which is good. Right now, like I said, we think in general, most patients have the ability to respond well, but maybe over time we'll learn more about specific subgroups of patients who do respond a little bit better than others and things like that as well. And honestly, still data just said to go out and interfere our works, too. We still don't have everything about that. There's still active research and a number of labs out there to sort of help detail how this really does benefit these interferon patients. Science. It's going to be cool to follow this. Absolutely. Thank you so much for being here. We believe in the educated consumer, educated patients. Absolutely. Thank you so much for contributing to that and hats off to you and all of your work. You get to say, "Interferon every single day," which is kind of cool. Absolutely. Thank you, Dr. Hunter. I appreciate it. Absolutely. Well, thank you, Dr. Tony Hunter, for contributing to today's episode. Thank you, Amy, for that very illuminating interview. I appreciate that you approach it as though a three-year-old—that's the level that I can comprehend things on. And thank you to our sponsor, Farma Ascensia, without whom this episode would not be possible. Thank you, Farma Ascensia. If you're not already listening to the PV pod stories from the marrow, listen to the latest from PV pod stories from the marrow. You will find it anywhere. You get podcasts. You can also follow links in the program notes. Amy Board, Bloodstream Podcast will be back with a regularly scheduled episode. A little less exciting, but so pretty important. I know. You're going to be so bummed that it's just normal. Amy Board, any final words for our audience before we sign off? No, I just think it's cool learning about stuff. I think it's cool learning about stuff. Science is cool. And it's sciencefair.org if you needed another interesting place to go for science education. Amy Board leads that too. We will be back with a regularly scheduled bloodstream episode next time, but with that, that is all for this episode. Be sure to subscribe to the Bloodstream Podcast and the PV pod stories from the marrow wherever you get your podcasts to get the next episode the moment it goes live. And loyal listeners, as always, email us at mailbagabletstreammedia.com and just tell us all of your grievances and all of your things. We want to know your stories. And we want to make sure that they get out to the world. So find us on social media as well. PJ L and I are on social media as well as bloodstream. Send any of those you want to mailbagabletstreammedia.com. I am your host, Patrick Jameslyn. And I am your other host, Amy Board. And until next time, take self care of yourself. Bye, everybody. Bye-bye.