MPN Treatments & Clinical Trials Update

Living Strong with MPN Part 1

• MPNs include PV, ET, and MF — related but different blood cancers.

• Genetic testing (JAK2, CALR, MPL) helps guide diagnosis and risk.

• Treatments vary by type and risk, including JAK inhibitors and phlebotomy.

• Symptoms like fatigue, itching, and spleen issues should be tracked closely.

• Clinical trials are encouraged and may offer early access to new options.

• Staying informed and seeing an MPN specialist makes a big difference.

Tiffany Drummond: Hello everyone! Thank you all so much for joining us this evening for our Living Strong with MPN program. I am so happy to see this full house. My name is Tiffany — I lead community programming and partnerships with The Patient Story. I know that MPN can be a challenging journey for patients and caregivers, and so I wanted to start by introducing you to a fellow MPN survivor. His name is Andrew Schorr. He is a myelofibrosis survivor, and he shared this message with us.

Andrew Schorr: Hello Saint Louis — or wherever you may be watching from. I’m Andrew Schorr, joining you from Del Mar, California, in San Diego County. I’ve been living with an MPN since 2011. I actually have a doctor’s appointment today with my MPN specialist. We’re going to go over my situation — I’m taking one of the JAK inhibitors, and a few weeks ago I had a bone marrow biopsy so they could look at the genomics of my cancer and see if things are progressing.

I wanted to talk for a few minutes about living with an MPN — whether that’s ET, PV, or, in my case, myelofibrosis. I’m grateful that I’ve been living pretty well with myelofibrosis since 2011, and treatments have been working. We’re at an exciting time now because things are changing. When I was first diagnosed, the first JAK inhibitor had just been approved. What’s happened since then is a real progression of science — understanding what drives progression from ET to PV to MF, and recognizing that we’re all different. Different patients need different medicines at different points in their journey.

I’m really encouraged. When I was first diagnosed, I didn’t know how long I’d live with this. I knew it was a serious, rare condition, and I knew it was important to connect with a specialist. Dr. Oh and his colleagues are great examples of that — not every doctor sees these conditions very often, and they may not be up on all the latest options. So I always say: go to a specialist.

That also opens up another possibility — clinical trials. A clinical trial is how we get new medicines and test whether they work. I was in a clinical trial years ago for another condition, and it led to much better care and lasting benefit. I’m a big fan. They monitor you closely — you feel like a VIP. You may need extra tests, but they’re looking at you with a magnifying glass, and you might get tomorrow’s medicine today. Whether you’re in a clinical trial or not, we now have an increasing number of FDA-approved options. We’re on a journey — with the researchers, the doctors, and with other patients — to get the best care for each of us.

So stay informed — that’s what you’re doing today. You’re learning what’s latest, and then you’ll discuss it with your healthcare team. Could be a new treatment, a clinical trial, or just continuing to monitor your current plan. ET, PV, and MF are different but related conditions, and they can progress from one to another. That’s why monitoring is so important. Have frank, recurring conversations with your MPN specialist, and don’t be afraid of clinical trials. That’s my perspective from living with myelofibrosis since 2011 — and I’d like to say that knowledge can be the best medicine of all.

Tiffany Drummond: Please give it up for Andrew Schorr. I believe that sharing our experiences has major impact for others — and that’s something The Patient Story is committed to. Now I’d like to introduce our moderator for the evening, Josh Bollam, Director of Patient and Community Outreach in the Saint Louis area for the Leukemia and Lymphoma Society — better known as LLS. Josh, take it away.

Josh Bollam: It’s my pleasure to be here. I’ve been with LLS for eight years. Nine years ago, I started my blood cancer journey as a caregiver alongside my mother for my uncle, who was diagnosed with non-Hodgkin’s lymphoma. We eventually placed him in a clinical trial at City of Hope, and while I was there I found a posting on the LLS website that said “work with us.” I clicked it, and eight years later, here I am.

LLS is here to support blood cancer patients. Our mission begins with cure — our goal is to cure blood cancers, and until that day comes, to support patients at every stage of their journey. We know cancer affects patients physically, mentally, and financially, and we’re here to help at every stage.

Tonight’s program is produced by The Patient Story, an organization dedicated to building community for patients and families through education and content. I encourage you to visit their site, where you can find hundreds of patient stories. We’d like to thank our collaborators — the Leukemia and Lymphoma Society and Imerman Angels — as well as the Cancer Support Community and MPN Research Foundation for helping promote this program. We also thank our sponsors — Sobi, Karyopharm, GSK, and Novartis — for their support. As always, sponsors have no editorial control over the content.

While we hope you learn a great deal tonight, our discussions are not a substitute for seeking medical advice from your own doctor. Please speak with your doctor about what’s most appropriate for you.

Now, let’s meet our panel. We have two special guests tonight. Dr. Stephen Oh is an Associate Professor of Medicine and Co-Chief of the Division of Hematology at Washington University School of Medicine. His clinical practice and research are focused on myeloproliferative neoplasms — MPNs. We also have Dr. Amy Zhou, an Associate Professor of Medicine in the Division of Hematology at Washington University in Saint Louis. She sees patients with a variety of hematological disorders, and her research focuses on developing new therapies and improving care for MPN patients.

Tonight we’ll cover the three MPN types — polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) — along with molecular testing, monitoring and managing symptoms, and the latest treatments including clinical trials.

Dr. Oh, can you briefly describe the differences and similarities between the three types of MPNs — including the distinction between primary and secondary myelofibrosis?

Dr. Stephen Oh: Absolutely. These three diseases are grouped together for several reasons. They all involve abnormalities of the blood counts. In polycythemia vera (PV), the primary feature is too many red blood cells — an elevated hemoglobin and hematocrit. White blood cell and platelet counts may be elevated too, but the red cell elevation is the defining feature. In essential thrombocythemia (ET), the primary feature is an elevated platelet count, though other blood counts may also be affected.

Myelofibrosis shares some of those features but is more typically associated with a decrease in hemoglobin — anemia. Patients with myelofibrosis often have more prominent symptoms: fatigue, night sweats, poor appetite, weight loss, and an enlarged spleen. Spleen enlargement can happen in PV and ET too, but it’s particularly common and prominent in myelofibrosis, causing abdominal discomfort and affecting appetite.

As you mentioned, myelofibrosis can be primary — meaning there was no prior blood disorder — or it can develop after a history of PV or ET. Patients with PV or ET may live for many years or even decades with no progression, but in some cases the disease does eventually progress to myelofibrosis. That’s called post-PV or post-ET myelofibrosis, also known as secondary myelofibrosis.

These diseases also share similar genetic or molecular abnormalities. The most common is a mutation in the JAK2 gene — specifically the JAK2 V617F mutation. It’s present in the vast majority of PV patients, and in about 50–60% of ET and myelofibrosis patients. For those without JAK2 V617F, the next most common mutation is in a gene called CALR (calreticulin), found in about 20–30% of ET and MF patients. Less commonly, there are mutations in MPL. We refer to JAK2, CALR, and MPL as the three primary driver mutations — most, though not all, patients with these diseases have one of the three.

Josh Bollam: What is the role of molecular testing in managing MPNs — in terms of getting a more accurate diagnosis, assessing risk of progression, or informing earlier treatment decisions?

Dr. Amy Zhou: To build on what Dr. Oh said — the three main driver mutations are very helpful diagnostically, because most MPN patients will have one of them. For the small percentage who don’t, we can use extended mutational testing called next generation sequencing. These broader panels include many more mutations that aren’t MPN-specific, but can still help confirm that a blood cancer is present — which is important information alongside blood count abnormalities or a bone marrow biopsy.

Beyond diagnosis, we’re learning that different mutations also carry different prognostic significance. These mutations are being incorporated into the risk stratification models for these diseases — combining them with blood counts and other features to better predict how patients will do over time. It’s not as personalized as we’d like yet, but that’s ultimately the goal as we understand these diseases more deeply.

Josh Bollam: How do those molecular tests influence your treatment decisions?

Dr. Amy Zhou: Right now, the specific mutations don’t necessarily dictate which treatment to choose from what’s currently available — but that may change in the future. As we discuss clinical trials, it may be that mutations will increasingly guide what treatment is best for a given patient.

Josh Bollam: Dr. Oh, what’s the difference between cytopenic myelofibrosis and proliferative myelofibrosis? What would you see differently in lab results, and do these differences impact prognosis?

Dr. Stephen Oh: These terms can sound confusing, but let’s break them down. “Proliferative” refers to the underlying feature of MPNs — the bone marrow is over-producing cells. In PV, you have high blood counts across the board. That’s proliferation. In the context of myelofibrosis, it gets a little more complex because patients can have some counts that are high and others that are low simultaneously.

“Cytopenic” essentially means low blood counts. Cytopenic MF is characterized by more prominent anemia and potentially low platelet counts (thrombocytopenia). Proliferative MF, by contrast, tends to appear in patients who previously had PV or ET — they started with higher counts and may be trending down, but their counts are still relatively higher than primary MF patients, whose counts tend to be lower from the start.

Josh Bollam: Are there unique challenges in treating those two groups?

Dr. Stephen Oh: Absolutely. Many of the available MF treatments can lower blood counts further. If counts are already low, that creates real limitations — it constrains the doses you can use, and low platelet counts in particular put patients at higher risk for bleeding. So we have to factor all of that in when deciding which treatment options to recommend.

Josh Bollam: Clinics use symptom assessment forms to track and monitor symptoms. How can patients monitor their symptoms at home? What tools are available, and how might symptoms change over time?

Dr. Amy Zhou: The symptom assessment forms we use in clinic are available online, and there are also MPN-specific symptom tracker apps you can download on your phone. These allow you to log and follow your own symptoms between visits. The key symptoms we want patients to flag — especially if they’re worsening — are persistent night sweats, bone pain, weight loss, and itching. These can be signs that the disease is changing, which may prompt a treatment review.

Josh Bollam: The Leukemia and Lymphoma Society also offers a free Health Manager app, available in all app stores. Let’s shift to treatments. Dr. Amy Zhou, can you provide an overview of current treatments for PV and ET, and your experience with their effectiveness?

Dr. Amy Zhou: For PV, we risk-stratify patients into higher and lower risk groups — and that risk is specifically about blood clots. The prognosis for PV and ET patients is generally very favorable, and most patients live a long time with these diseases. But one of the biggest complications is an elevated risk of blood clots — including heart attacks, strokes, deep vein clots, and pulmonary embolism. Much of our treatment is aimed at reducing that risk.

Risk stratification comes down to two main factors: age over 60, and prior history of a blood clot. Higher-risk patients need treatment to lower the hematocrit — for PV, our goal is to keep it below 45. Lower-risk patients typically manage with aspirin and therapeutic phlebotomy (periodic blood removal to maintain that hematocrit goal).

For higher-risk PV patients, the most common medication is hydroxyurea — a well-tolerated pill. Interferon is another option, given by injection. Ruxolitinib (brand name Jakafi), a JAK inhibitor also used for myelofibrosis, is FDA-approved as a second-line option for PV — meaning for patients who can’t tolerate hydroxyurea or aren’t responding adequately to it.

For ET, risk stratification works similarly — age and blood clot history are the primary factors. We also consider mutations to some degree, since JAK2-mutated ET patients have a somewhat different clotting risk profile than CALR-mutated patients. Treatment options for ET overlap with PV: hydroxyurea is commonly used, anagrelide is a second-line option for lowering platelet counts, interferon can be used as well, and I have used ruxolitinib off-label for some ET patients — though insurance coverage can be challenging since it’s not FDA-approved for that specific indication.

Josh Bollam: Dr. Oh, can you give an overview of myelofibrosis risk categories — low, intermediate, and high — and how that shapes treatment?

Dr. Stephen Oh: We have several prognostic calculators that categorize MF patients into roughly four or five risk categories, from lower to higher risk. These help us understand overall disease outlook — projected survival, and the possibility of progression, including in the most advanced cases to acute leukemia.

Risk category guides treatment recommendations. For highest-risk patients who are otherwise relatively healthy, we might actually recommend a consultation with bone marrow transplant specialists. Transplant is an intensive option, but it has the potential to put the disease into remission. That said, most patients aren’t candidates for transplant due to age or other medical issues.

For intermediate and high-risk patients not pursuing transplant, we have four FDA-approved oral JAK inhibitors for myelofibrosis: ruxolitinib (Jakafi) — the first approved; fedratinib (Inrebic); pacritinib (Vonjo); and most recently momelotinib (Ojara). As a class, these drugs are particularly effective for symptoms — reducing fatigue, night sweats, and spleen-related discomfort, sometimes with dramatic improvement. That’s why we’ve increasingly relied on them over the years.

Josh Bollam: Speaking of symptoms — fatigue in particular. What are the most effective strategies for managing it? Any specific medications or lifestyle modifications?

Dr. Stephen Oh: The JAK inhibitors tend to help quite a bit with fatigue and energy, sometimes with marked improvement. We also have to recognize that fatigue is multifactorial — it can stem from the disease itself, from anemia, or from other causes entirely. So we need to be thorough. As for lifestyle, we encourage patients to stay as active as possible — though of course there are real limits when someone is severely anemic or symptomatic. Every individual has to find what’s reasonable for them.

Dr. Amy Zhou: I agree completely — nothing to add.

Josh Bollam: Outside of anemia, what other common symptoms do MPN patients present with, and how are they managed?

Dr. Amy Zhou: It really depends on the specific MPN. For myelofibrosis patients, an enlarged spleen and constitutional symptoms — fatigue, night sweats, itching — are common in addition to anemia. For ET and PV patients, anemia and significant spleen enlargement are less typical, but itching and other constitutional symptoms can still occur.

Josh Bollam: Let’s focus on anemia specifically, since it’s significant in this patient population. How does it impact treatment approaches, and what clinical signs should prompt more frequent evaluation or a change in strategy?

Dr. Stephen Oh: Anemia can be a major problem, particularly in myelofibrosis. It may start mild and worsen over time, eventually requiring red blood cell transfusions — sometimes occasionally, sometimes more frequently. It’s also worth noting that anemia can have other causes beyond the disease itself. I saw a patient just this morning whose anemia was due to iron deficiency from GI bleeding — so we always need to look for contributing factors.

When it comes to disease-related anemia, it’s significant on multiple levels. In MF, anemia is a key component of all the major prognostic scoring systems — it’s a marker of more severe disease. It contributes directly to fatigue. And some treatments, like ruxolitinib, can actually worsen anemia, even while improving how the patient feels overall. We accept that trade-off, but it remains a real challenge. Some of the newer therapies have different effects on anemia, and there are emerging strategies to more directly address it — which we’ll talk more about.

Living Strong with MPN Part 2

Drs. Stephen Oh and Amy Zhou shared updates on several phase 3 clinical trials for myelofibrosis (MF):

• Pelabresib + Ruxolitinib (Jakafi) showed superior spleen reduction but unclear symptom benefit.

• Navitoclax + Ruxolitinib (Jakafi) also improved spleen size but with increased blood count-related side effects.

• Selinexor (Xpovio) and Navtemadlin are other emerging therapies under evaluation.

Clinical trials always include a standard of care (like Ruxolitinib), and “placebo” often refers to an add-on rather than no treatment at all.

Looking forward, the panel highlighted efforts in personalized medicine, especially for patients with CALR mutations (e.g., CALR-targeted antibodies). Researchers are working to better tailor treatments based on a person’s genetic profile, but most current therapies aren’t yet mutation-specific.

The doctors addressed:

• Anemia and transfusion dependence as major concerns in MF prognosis.

• Support for rural patients, including partnering with local doctors and offering travel reimbursement for trial participation.

• Equity in access and the need for continued outreach to underserved communities.

• Younger patients facing fertility challenges and different treatment needs.

Josh Bollam: We know that clinical trials can be overwhelming and confusing. That’s why LLS has created a dedicated service to answer your questions and help guide you through the process — to be an extension of your healthcare team. To learn more, we’ll now hear from Tiffany, who manages community programming at The Patient Story, as she interviews LLS nurse navigator Melanie Fife.

Tiffany Drummond: Welcome, everyone. My name is Tiffany, and I manage community programming at The Patient Story, where we’re committed to bringing human answers to your cancer questions. Today we’re going to discuss a specific service that helps bring innovative therapies to blood cancer patients: the LLS Clinical Trial Support Center. I have the pleasure of speaking with nurse navigator Melanie Fife, who will share more about this resource. Welcome, Melanie!

Melanie Fife: I’m doing great — glad to be here.

Tiffany Drummond: Can you explain what clinical trial nurse navigation is, especially given the complexities of the healthcare system?

Melanie Fife: Of course. Clinical trial nurse navigation is a service that helps patients and families navigate the clinical trial process. Patients work with trained registered nurses who act as guides — helping them understand clinical trials, search for trials that may be a fit, and overcome any barriers to participating. These navigators provide personalized, one-on-one support and serve as a resource for questions and education throughout the patient’s cancer journey.

Tiffany Drummond: Are all of the navigators registered nurses, or is there a variety of credentials?

Melanie Fife: Everyone is a registered nurse, but we have a range of credentials — some have their master’s degrees, some have been nurse practitioners or clinical nurse specialists.

Tiffany Drummond: What can you tell us specifically about the LLS Clinical Trial Support Center?

Melanie Fife: The LLS Clinical Trial Support Center is committed to helping patients actually access clinical trials. It’s a free, personalized service that includes several things: personalized clinical trial matching, where we work one-on-one with patients to identify trials that fit their specific diagnosis, stage of disease, and other factors; education about clinical trials, including risks and benefits; help identifying potential treatment options and connecting patients with clinical trial site staff; and ongoing support, including connecting patients with our Information Resource Center and financial assistance programs. Ultimately, we’re here to build a web of support and guide patients through their cancer journey.

Tiffany Drummond: The internet is full of information that can be overwhelming for someone considering a clinical trial. What sets the LLS Clinical Trial Support Center apart from other resources?

Melanie Fife: I’m so glad you asked. We’re a team of 12 highly trained nurse navigators with expertise in both pediatric and adult blood cancers, and we are completely free — any patient, family member, or healthcare professional can reach out. We’re here to be an extension of the patient’s healthcare team, to educate, support, and empower patients to be active participants in their care. What really sets us apart is that personalized, ongoing relationship. We don’t just hand patients a long list of clinical trials. We take the time to get to know who they are, what their goals of care are, and where they are in their journey. We provide a tailored clinical trial report that takes into account their medical history, previous treatment responses, ability to travel, insurance type, and other life circumstances that can impact their ability to participate. We also do extensive outreach on the patient’s behalf — talking to pharmaceutical partners and clinical trial site staff, including principal investigators and coordinators — to ensure patients and families have the most up-to-date information to make informed decisions.

Tiffany Drummond: How can people get in contact with the Clinical Trial Support Center?

Melanie Fife: Patients and healthcare providers can reach us through our Information Resource Center by calling 1-800-955-4572, or by visiting lls.org. You can also email us directly with questions.

Tiffany Drummond: Melanie, in such a short time you’ve given us so much. Thank you for participating in our Living Strong with MPN program. Any closing thoughts?

Melanie Fife: Just thank you to you and The Patient Story for having us — and I hope everyone knows we’re here to help.

Tiffany Drummond: What a short but impactful conversation. Melanie’s insights have been invaluable. If you are interested in participating in a clinical trial, please take advantage of this service. And on behalf of The Patient Story, a special thank you to our audience here in Saint Louis and to everyone tuning in virtually. Enjoy the rest of the event.

Josh Bollam: Thanks to both Tiffany and Melanie for highlighting that incredible resource. The LLS Clinical Trial Support Center’s team of nurse navigators provides personalized service, helps match patients with suitable trials, and assists with the enrollment process. If you or someone you know is considering a clinical trial, please don’t hesitate to reach out.

Now let’s look at some of the active clinical trials underway and what they mean for patients. Dr. Oh, can you tell us about the Phase 3 MANIFEST-2 study of pelabresib?

Dr. Stephen Oh: Yes — and just to clarify the pronunciation, it’s “pelabresib.” The MANIFEST-2 study is a Phase 3 trial for patients with myelofibrosis in which patients were randomized into two groups — which is the standard design for Phase 3 studies. One group received ruxolitinib, the most common treatment for myelofibrosis, and the other received ruxolitinib plus pelabresib. The ruxolitinib-only group also received a placebo, so no one knows initially which group they’re in. That design allows us to determine whether pelabresib is actually adding something beneficial.

Just to back up a moment — Phase 3 is the most advanced stage of clinical trial development before FDA approval. Phase 1 studies are typically small and focused on establishing that a drug is safe and tolerable. Phase 2 begins to explore effectiveness. Phase 3 is where we definitively test whether the drug works at scale.

The initial results from MANIFEST-2 were reported at last year’s ASH meeting — the American Society of Hematology’s annual conference held every December. The headline finding was that patients receiving both drugs together showed clearly superior spleen reduction. We know ruxolitinib can shrink the spleen; the combination shrunk it even more. Spleen response is what we call the primary endpoint — the most important measure of whether a treatment is working — and on that measure, the combination was the winner.

The secondary endpoint was symptom improvement. Ruxolitinib helps with symptoms, so the question was whether adding pelabresib improved that further. The answer there was more mixed — some signals suggested modest additional benefit, but it wasn’t a clear-cut win. The study is ongoing, and more data is needed before we know whether this combination will move toward FDA approval.

Josh Bollam: I want to take a step back, because we have patients in the room and online at all different stages of their journey, and some may not have encountered clinical trials yet. One of my goals is to break down the myths around them. You used the word “placebo,” which sometimes causes concern. Can you talk about what participating in an MPN clinical trial actually looks like, and how standard of care is always part of the picture?

Dr. Stephen Oh: Absolutely. From a patient’s perspective, hearing that you might receive a placebo can raise real questions — why would I commit to all this extra time and monitoring if I might not even get the active treatment? That’s a completely legitimate concern, and it’s one reason many patients choose not to participate in clinical trials, and that’s understandable.

But a placebo comparison is genuinely necessary to determine whether a new treatment is effective. In earlier phases of a study, there typically is no placebo — every patient gets the study drug, which is attractive from that standpoint. But in Phase 3, some comparison is required. And as Josh was saying, in studies like MANIFEST-2, patients are always receiving standard of care at minimum. Every patient got ruxolitinib — at the time that study started, the predominant JAK inhibitor in use — and then received either the study drug or a placebo on top of that. So you could say every patient gets a good foundational treatment regardless of which group they’re in.

Josh Bollam: Can you talk about the status of BCL-2 inhibitors for myelofibrosis?

Dr. Amy Zhou: Sure. Navitoclax is a BCL-2 inhibitor that was also presented at last year’s ASH meeting in a Phase 3 study with a very similar design — adding it on top of ruxolitinib versus ruxolitinib alone. Like the pelabresib study, there was a bigger spleen response with the combination. Symptom improvement was again not dramatically different between the two groups. One safety consideration with the combination was lower blood counts, which is a real concern when thinking about whether the added benefit outweighs the added risk. As far as I’m aware, there’s no FDA approval decision yet for navitoclax, so we’ll see how that progresses.

Josh Bollam: What about the CENTURY study for selinexor?

Dr. Stephen Oh: Selinexor is currently FDA approved for a subset of patients with multiple myeloma, and it’s now being explored for myelofibrosis. The approach in myelofibrosis uses lower doses than in myeloma, which may reduce some of the side effect concerns seen in that setting. There is a Phase 3 study now underway in myelofibrosis, based on promising earlier phase results, and it’s again in combination with ruxolitinib — very similar in design to the other studies we’ve discussed. We’re not currently participating in that trial at our site, but we’re watching it with interest.

Josh Bollam: And lastly, what are the developments around CR 232?

Dr. Stephen Oh: CR 232, also known as navtemadlin, is another agent being explored in myelofibrosis. It’s now in Phase 3 as well. There’s data coming out of earlier phase studies suggesting it may not only improve spleen size and symptoms, but also affect some of the underlying disease biology — which is appealing. We’ll see how the Phase 3 study progresses. And broadly, I want to note for patients whose primary concern is PV — this isn’t all about myelofibrosis. These examples simply illustrate that there are a number of novel agents in various phases of development, quite different from JAK inhibitors, moving through clinical trials across all three MPN types.

Josh Bollam: Now to my favorite part — the future. Where do you see MPN treatments in 5 to 10 years? What are the key areas of focus that researchers are zeroing in on?

Dr. Stephen Oh: I’ll start with the CALR mutation, which Dr. Zhou mentioned earlier. Patients with ET and myelofibrosis who are CALR-positive tend to have somewhat more favorable disease overall — lower blood clot risk, generally lower-risk disease. But that said, these diseases can still cause real problems, and we’d love to have more effective therapies for all patients. There are now several strategies entering early-phase development that are very specifically targeted to the CALR mutation — a truly personalized medicine approach. We just opened a CALR-specific antibody study at our site. Patients with ET or MF who have the CALR mutation may be eligible if they meet the other criteria. It’s an example of a treatment that might have a profound effect on the disease and be more effective than what we have currently. There are other CALR-targeted treatments in early development as well. It’s a very exciting time for that kind of personalized approach.

Josh Bollam: Dr. Zhou, can you give us a high-level overview of personalized medicine and how you see genetic testing being used to tailor treatment approaches going forward?

Dr. Amy Zhou: Right now, current therapies are still relatively broad — we don’t necessarily use a patient’s mutational status to decide which JAK inhibitor to prescribe, for example. But I do foresee that changing. As more treatments become available, I hope the future involves therapies that are more specifically targeted to the mutations a patient carries. That’s still a work in progress, but it’s where the field is heading.

Josh Bollam: MPNs — like many blood cancers — have historically been seen as a disease of older adults, but we’re increasingly seeing younger patients being diagnosed. What does “younger” mean in this context, how might this demographic shift impact treatment approaches and clinical trial design, and are there unique challenges or opportunities in treating younger MPN patients?

Dr. Stephen Oh: This is an important topic. Historically, the majority of MPN diagnoses have been in older adults — however you define that. But we are increasingly diagnosing younger patients, partly due to greater awareness and recognition. And there’s fascinating research suggesting that some patients may have carried the JAK2 mutation for decades before a diagnosis is ever made — possibly acquiring it in their 20s but not being diagnosed until 60. So the disease may be brewing silently for years.

For younger patients, we know that PV and ET can be very stable for 20, 30, even 40-plus years. That’s actually reassuring. But it also means living with the disease for a very long time, and during that time, complications could occur at any point. It reinforces the need to be proactive, think ahead, and stay engaged with your care. It also motivates the field to ask: can we treat these diseases earlier, with safer therapies, in a way that prevents long-term complications from ever developing?

Dr. Amy Zhou: I’d add that younger patients bring some unique considerations that aren’t always top of mind with older patients — particularly around fertility. Some of the medications we prescribe can affect fertility, so we make sure younger patients are connected with one of our fertility specialists. Managing patients through pregnancy is another example of something specific to this population that requires careful balancing of safety and disease management.

Josh Bollam: We have some questions from the audience. First, online: what causes patients to become anemic and need transfusions?

Dr. Amy Zhou: In myelofibrosis, anemia is a common complication, and the mechanisms behind it are multifactorial — there are many factors that contribute to its development and worsening over time. Transfusion dependence is considered a worse prognostic factor and is incorporated into the risk stratification systems we use for MF patients when estimating risk for progression to acute leukemia or overall survival.

Audience member: I was told by Dr. Oh that I acquired my CALR mutation — it’s not hereditary. Is that correct?

Dr. Stephen Oh: Yes — and let me clarify this for everyone. The question is whether someone is born with this mutation, or whether they acquire it during their lifetime. The answer applies to CALR, JAK2, and MPL: these are generally not mutations you’re born with, and they’re not passed down from parent to child the way inherited genetic diseases are. What we believe happens is that at some point a blood cell acquires the mutation, and over time, the cells carrying that mutation expand until the disease becomes apparent.

I’ll note that some research suggests the mutation may be acquired years or even decades before the disease is detected — but that doesn’t change the fundamental point that it’s not a heritable mutation passed from parent to child. So the common follow-up question — “Do I need to worry about my kids? Should I get them tested?” — the answer is no. They’re not going to inherit it from you.

That said, there is a slightly elevated risk among first-degree relatives — siblings and children — of developing a similar disorder. We do see families where multiple members have one of these conditions, and one might have PV while another has ET. The risk is on the order of 2-to-4 fold higher than the general population. But since these diseases occur in roughly 1-2 out of every 100,000 people, even 4 times that is still quite uncommon — around 4 per 100,000. For that reason, routine screening of family members is not recommended. The elevated risk likely reflects some other shared genetic predisposition, not the JAK2 or CALR mutation itself being transmitted.

Audience member: Are these diseases influenced by the environment?

Dr. Stephen Oh: That’s a great question. These diseases are fundamentally driven by acquired mutations, but we are increasingly seeing evidence that the environment may play a role in how they develop and progress. One area my research group has been exploring is inflammation — a broad concept, but the idea is that abnormal inflammatory states may influence the disease course and progression, even if they don’t cause the disease outright. We also think about infections: if a patient carries a JAK2 mutation at a low level, why does it expand rapidly in some people over ten years but stay flat in others? Environmental factors — perhaps a severe viral infection, for example — may be contributing. This is still largely theory and early research rather than hard evidence, but it’s an area we’re paying increasing attention to.

Josh Bollam: Online question from Gail, for Dr. Zhou: what treatments might delay progression, especially for ET patients with few symptoms but high platelets?

Dr. Amy Zhou: In terms of progression to myelofibrosis or acute leukemia — right now, honestly, it’s not clear that any currently available therapy definitively reduces that risk. There is a lot of interest in interferons for PV and ET, and their potential disease-modifying properties. One thing interferons can do is reduce the amount of detectable JAK2 mutation in the blood over time — sometimes to undetectable levels. But whether that translates into a meaningful reduction in the risk of progression or improved long-term survival isn’t yet established with hard clinical data. Part of the challenge is that ET patients do so well overall that any trial examining those long-term endpoints would need to follow patients for a very, very long time. So that data simply doesn’t exist yet. My honest answer is: there is no treatment we currently recommend specifically to prevent progression, though this is an active area of research.

Audience member: Are there email lists or forums where patients can connect and share their experiences?

Josh Bollam: I’d recommend the LLS Patient Community — our patient forum and social media platform. It has dedicated forums for all blood cancer diagnoses, including subcategories for each of the major MPN types, as well as forums covering treatment topics and psychosocial subjects. You can also connect with patients from other communities around the country. The best part: it’s monitored every day by an LLS information specialist — one of our nurses or social workers — so if something is posted in error or needs clarification, they’re there to add accurate, reliable information. It’s a much better option than asking Dr. Google.

Dr. Stephen Oh: I’d also mention the MPN Research Foundation, which has excellent information on their website, and MPN Advocacy — easily found with a Google search. Both have newsletters and email updates you can subscribe to. There are also active Facebook groups for MPN patients that many people find genuinely helpful. My only note of caution: if you find online communities amplify your anxiety more than they help you, that’s worth paying attention to. These tools can be powerful support resources, but they’re not for everyone.

Audience member: Is stem cell transplant always a last resort, or do you ever recommend it proactively — for instance, for a myelofibrosis patient before it progresses to leukemia?

Dr. Stephen Oh: Great question, and one I have a nuanced view on. As a non-transplant specialist, I tend to focus on optimizing medical therapies to avoid the substantial risks of transplant. But wearing the hat of a transplant specialist, the honest argument is that transplant is currently the one treatment with the potential for long-term disease-free remission — and in the best cases, possibly even cure. So it’s not a last resort. We do choose carefully: patients who we think are in true need of transplant and who are healthy enough to withstand the risks. It’s very patient-specific, and it’s a decision made in close consultation with our transplant colleagues. But the goal is not to wait until the very end — it’s to identify the right patients at the right time.

Josh Bollam: I want to ask about equitable access, which is something near to my heart. Many patients — especially those in rural areas or underserved communities — may never even hear about a clinical trial. They’re receiving care at a local community oncology office. What can be done to address those barriers?

Dr. Amy Zhou: I’ll be honest — I don’t have a perfect solution. MPNs are a rare disease, so even community oncologists who see many cancer types may not be as up to date on the latest MPN therapies as a specialist would be. Dr. Oh and I have participated in education geared toward our community colleagues, and we’re always available to provide guidance if a patient’s local provider reaches out with questions — even if the patient can’t travel to see us in Saint Louis. For things like clinical trials or transplant that require coming to an academic center, it’s a real logistical challenge. Siteman does offer housing resources for patients who need to travel and stay overnight, and those kinds of supports can make a difference. But I won’t pretend it’s fully solved.

Dr. Stephen Oh: I’d add that for patients who are enrolled in clinical trials, we do try hard to minimize the burden. We offer mileage reimbursement, funds for meals, and in some cases hotel support for longer visits. We also try to build individualized care arrangements between the patient, our team, and a local physician — alternating visits, coordinating blood count monitoring at a lab near the patient’s home, and making sure that distance doesn’t become an insurmountable barrier. Our whole team — clinical and research staff — works to make that possible.

Audience member (patient): I had myelofibrosis for ten years before my local provider attended a webinar featuring Dr. Oh and referred me to him. I live in a rural area. Once I came in, they took my files, analyzed them, called me back, and made my appointment. Within two to four weeks I spoke with Dr. Oh three times by phone. He told me I had the CALR mutation and explained that among ET patients, the CALR mutation is associated with the best long-term outcomes. I think people in rural areas should know it’s worth making the drive — even two, three, four hours — to get a specialist’s opinion.

Josh Bollam: Your story leads to a great question. For patients who are driving an hour or two for appointments, how can they make the most of their time with their healthcare team — especially if they can’t come in as frequently?

Dr. Stephen Oh: We recognize every patient has specific circumstances and logistical constraints. One thing I’ll highlight: for clinical trials, we strive to provide travel support — mileage reimbursement, meal funds, and hotel stays for longer visits — to make participation as feasible as possible. Beyond that, we try to build a real partnership between the patient, our team, and a local physician. That might look like seeing a local provider frequently and coming to us once a year; or alternating every six months between providers; or having blood counts monitored at a lab close to home so we can get the results without the patient having to travel every time. We tailor it to the individual. And our whole team makes that possible.

Josh Bollam: Dr. Zhou, when you’re meeting a newly diagnosed patient for the first time, what do you recommend to help them make the most of that appointment and retain the information?

Dr. Amy Zhou: New patient visits can be overwhelming. There’s a lot of new information coming at once, and it can be very hard to process all of it in 30 minutes. I always tell patients: this is a lot of information, and it’s okay if you don’t absorb everything right now. You don’t have to ask every question in that first visit. You can call us, send a message through MyChart, or reach out however is easiest — we’re accessible. Think of your questions as they come to you and don’t wait until your next appointment. I’ve also had patients ask me to write things down in their after-visit summary, and I’m happy to do that. The goal is to make sure patients feel they have ongoing access, not that they have one chance to get everything right.

Josh Bollam: You mentioned MyChart — something that’s become much more common over the last decade. Test results can appear in a patient’s portal before the doctor has had a chance to discuss them. How do you advise patients to handle that?

Dr. Amy Zhou: My general advice is: don’t try to interpret your own test results. I will reach out and explain them, and we’ll discuss it together. Don’t turn to Dr. Google to interpret your lab values — let me provide that context.

Dr. Stephen Oh: It’s an evolving dynamic. Sometimes a result shows as “resulted” in MyChart but isn’t yet viewable because the doctor needs to sign off first — and just knowing something is there but not being able to see it creates stress. I understand that. The most productive approach, generally, is to have results explained in context by your care team, especially for anything complex. That said, each patient-provider relationship is different, and what works best will vary.

Audience member: What are we doing about a cure? When you talk about curing these diseases, are you looking at bringing the allele burden down to zero? Or is allele burden even relevant to that goal? Everything we’ve discussed tonight is about living with the disease and managing symptoms — but what about actually ringing that bell and being done?

Dr. Stephen Oh: That’s one of the most important questions in the field, and I want you to know it’s very much on our minds. On one hand, for many patients, existing therapies can keep the disease stable for years or decades — and that’s genuinely good. But we want to reach a higher bar. In myelofibrosis, we have four FDA-approved drugs that help with symptoms and other disease features, and they’re valuable — but they’re not the end goal. We need treatments capable of doing more.

To your specific question: yes, reducing the mutation burden to zero — or undetectable — is very much part of the goal. The interferon drugs can do this in some patients, and there’s active discussion in the research community about what it means when that happens. Does it constitute a cure in those patients? We don’t fully know yet. But it’s being seriously studied. The short answer is: cure is absolutely the goal, and the field is moving toward it with increasing urgency. It will take continued research and time, but we’re committed to it.

Josh Bollam: I’d like to close with one final question. What would you say to your MPN patients today that you would not have been able to say to them ten years ago?

Dr. Stephen Oh: Ten years ago — 2014 — we had exactly one approved treatment for myelofibrosis: ruxolitinib. Today we have four JAK inhibitors approved for MF, interferon approved for polycythemia vera, and more on the way. That’s a remarkable amount of progress. And I think ten years ago, I was giving patients the same message I’d give today: I’m very optimistic. In the next ten years, we’re going to make even more progress. This field is the focus of intense research — in the laboratory and in clinical trials — and I fully anticipate major advancements in the decade ahead.

Dr. Amy Zhou: I share that optimism completely. The availability of new therapies over the past ten years has been significant. And the advances in molecular testing and prognostic scoring — incorporating different mutation types into how we predict disease course — those tools barely existed ten years ago. I’m very excited to see what the next ten years holds, both in terms of new therapies and the continued development of truly personalized medicine as we understand these diseases more deeply.