Tag Archive for: myeloproliferative neoplasm

Myelofibrosis Clinical Trials | The Benefits of Patient Participation

How do clinical trials fit into a myelofibrosis treatment plan? Dr. Idoroenyi Amanam discusses the benefits of clinical trial participation and advice for patients who may be hesitant to join a trial. 

Dr. Idoroenyi Amanam is a specialist in myeloproliferative disorders and is an Assistant Professor in the Division of Leukemia at City of Hope. Learn more about Dr. Amanam.

Download Resource Guide

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How Can You Learn More About Myelofibrosis Clinical Trials?

How Can You Learn More About Myelofibrosis Clinical Trials?

Transcript:

Katherine Banwell:

Dr. Amanam, where do clinical trials fit into a myelofibrosis treatment plan?  

Dr. Idoroenyi Amanam:

When you think about where we’re at right now in myelofibrosis, I think  from the scientific standpoint, it’s really exciting.  We’re understanding this disease so much better.  We have  a much clearer picture of how this disease works.  

But with that said, unfortunately, when you look at the drugs that we have available to us, we don’t really have that many still,  and so clinical trials play a big part in this disease space. Because there’s patients who are  very advanced when we diagnose them, and our FDA-approved therapies may not really make a big dent in their symptomology, may not change  what happens with the disease moving forward. And so, clinical trials do give patients such as that an opportunity to actually  get the disease under control. 

Katherine Banwell:

Well, as you mentioned, patients participating in trials are key to moving research forward, right? Can you talk about the benefits of clinical trial participation?  

Even though it – 

Dr. Idoroenyi Amanam:

Yeah – 

Katherine Banwell:

– might be scary for a lot of people. 

Dr. Idoroenyi Amanam:

Right, right. 

Katherine Banwell:

I think a lot of people still think, “Oh, I’m just going to get a placebo, and it’s not going to help me in any way,” but that isn’t really the case anymore, is it? 

Dr. Idoroenyi Amanam:

It’s not the case.  And I think the way that you can think about trials are, we use trials to give therapies that we view as very promising to patients who fall in a gap. And that gap may be that, even though we have FDA-approved drugs, we know that those drugs really may not work for that specific patient. And so, we have an understanding from either a different type of disease that’s very similar to myelofibrosis, or  our  scientific experience that there is a therapy that will work. And we want to use trials to be able to give that patient a chance to, kind of, get over that hump. 

And so, in today’s era, we don’t structure trials around therapies that we don’t believe actually work or  getting patients in trouble down the line. And so, we really, really do believe that our trials are, kind of, an extension of what we have currently  on the market, and so it is a part of our everyday armamentarium to fight this tough cancer. 

Katherine Banwell:

What would you say to patients who are hesitant of participating in a trial?  

Dr. Idoroenyi Amanam:

One, I’d really want to get a clear sense of what their hesitance is.  Is it that the trial would put them at higher risk for some sort of toxicity?  Is it that they’re worried that there’s some other therapy that’s out there that, potentially, would give them a better chance at fighting this disease? the third part of it, the unknown, is always scary for many people.  

And I think my job is to be a part of a patient’s team.  Talk through those concerns, get a sense if this is something that really is the best thing for them, or do we have something else that might be a better option? And unfortunately, there are some instances where I do believe the trial is the best option for a patient, but the patient does not feel comfortable, and we have to go down another path.  

And all of us, we will never force a patient to go down a path that they don’t feel comfortable with. We all believe in patient autonomy, but there are some instances where   the trial may be the best opportunity, and I will do my best job to advocate for that and come to a decision together with the patient. 

Why Myelofibrosis Patients Should Be Engaged in Their Care Decisions

Dr. Idoroenyi Amanam, a myeloproliferative disorder specialist and researcher from City of Hope, shares expert perspective on the importance of patient participation in care and treatment decisions. Dr. Amanam emphasizes the necessity of having a care partner and utilizing all members of the healthcare team. 

Dr. Idoroenyi Amanam is a specialist in myeloproliferative disorders and is an Assistant Professor in the Division of Leukemia at City of Hope. Learn more about Dr. Amanam.

Download Resource Guide

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Promising Advances in Myelofibrosis Research | Optimism for Patients

Promising Advances in Myelofibrosis Research | Optimism for Patients

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Expert Outlook | New Myelofibrosis Therapies Showing Promise 

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Expert Perspective | A Concerted Effort to Advance Myelofibrosis Care

Transcript:

Katherine Banwell:

Well, how do you encourage patients and care partners to be involved in decision making? Do you have any advice for them?  

Dr. Idoroenyi Amanam:

That’s a very important question, and it’s a tough one. And I will tell you, personally, I have family members who have medical  disorders that I think do require a lot of support from other family or friends. And  based off my experience, I encourage patients to involve their families in these discussions, because I don’t think  we’re at a space where things are very binary.  

I think the decisions that we make when we’re treating patients with myeloproliferative disorders and myelofibrosis, there are some nuances there, and I think family can really help the providers, in addition to the patients, in coming to the right decision about how we’re going to move forward.  

So, I think my advice is, involve your family, involve your friends.  I think having a community of support is very important when you have a type of disease such as this. 

Katherine Banwell:

And it’s important to have somebody there with you, a care partner or a friend, as you say, who may be able to ask questions that you, as the patient, haven’t thought of. Somebody there to take notes, just in case you need to refer to something after. 

Dr. Idoroenyi Amanam:

Absolutely. Absolutely, I agree. I think it’s a team from both sides  to, kind of, extend what you’ve said. To the medical side, the pharmacist may give me some input about  some things I may have missed with the patient,  the nurse practitioner in clinic, the RN in clinic,  the other staff.  

And  I think it’s one of those situations where the more people involved can help us, kind of, draw that picture better. I think we’re trying to get a sense of how we can move forward in the best way, and having all of those parties being active and offering  the best that they can is really helpful for everyone. 

Promising Advances in Myelofibrosis Research | Optimism for Patients

 Dr. Idoroenyi Amanam from City of Hope discusses how the availability of newer JAK inhibitor therapies is providing better options for myelofibrosis patients. Dr. Amanam also shares how researchers are working to reduce the risk of disease progression and providing curative options for myelofibrosis.

Dr. Idoroenyi Amanam is a specialist in myeloproliferative disorders and is an Assistant Professor in the Division of Leukemia at City of Hope. Learn more about Dr. Amanam.

Download Resource Guide

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Myelofibrosis Clinical Trials | The Benefits of Patient Participation

Myelofibrosis Clinical Trials | The Benefits of Patient Participation

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Expert Perspective | A Concerted Effort to Advance Myelofibrosis Care

Updates in Myelofibrosis Research From an Expert

Updates in Myelofibrosis Research From an Expert 

Transcript:

Katherine Banwell:

Dr. Amanam the JAK inhibitor class of therapies often have side effects associated with them. What advancements are being made to manage these side effects? 

Dr. Idoroenyi Amanam:

Yeah. That’s a great question. And I would think about when these JAK inhibitors first  came out, I think we were all willing to accept the side effects because of the fact that you only had one JAK inhibitor, and then we now have more than one. We have a couple of JAK inhibitors, and I think the idea is that the biggest problem that we had with some of the JAK inhibitors were that  patients’ counts couldn’t tolerate higher doses of the JAK inhibitor.  

And we know that for some JAK inhibitors, you have to be at a baseline dose that will help with shrinking your spleen, or improving symptoms, and if you’re below that dose, it doesn’t work very well. And so,  we had a tough time   making adjustments based off of patients’ counts. And so, we have some newer JAK inhibitors that    patients tolerate    these drugs even though they have lower counts. And so, I think that’s one big change that we’ve all seen over the past five years.   

Katherine Banwell:

Is there anything else you’d like to add about advancements in myelofibrosis care?  

Dr. Idoroenyi Amanam:

I would say if we think about early stage, a patient who’s diagnosed, and they’re told that they’re early myelofibrosis, or what we really truly define as low risk myelofibrosis, we traditionally did not have any therapies for those patients, and I think that it’s exciting that we are in a space now where we are thinking about therapies for those patients, and therapies that will reduce the risk of progression to a more advanced stage of myelofibrosis.   

For patients who are in the middle, I think we’ve had a rapid expansion of therapies that are available to patients, and I think a lot of our clinical trials that are currently in play are really directed towards that group, and so that’s really exciting. And then for the high-risk patients, City of Hope is a bone marrow transplant center, cellular therapy center, and we have a lot of experience in performing allogeneic stem cell transplants for myelofibrosis patients.  

And I think across the country, we have gotten better at performing allogeneic stem cell transplants for myelofibrosis, and as of right now, it’s one of the few curative therapies that we have.  

And we have been able to understand how to get these patients through a very intense regiment and get them to the other side, and I think that’s also very exciting. We still have a lot of clinical trials in allogeneic stem cell transplant space as well. And so, I think we are in a place now where we have a therapy for everyone, if they choose to want one.  And not only a therapy just to bridge them, or treat their symptoms, but therapies that, potentially, will get rid of this disease.  

And I think for a patient, when you go to sleep at night, or when you talk with your family, the biggest worry is having something  that there’s no clear sense of we can get rid of it. And I think we’re getting to a better place where I can confidently tell patients we’re getting better at getting rid of this, and I think that’s the most exciting thing that we have right now.  

Katherine Banwell:

Yeah. It’s a promising field. 

Dr. Idoroenyi Amanam:

Very promising.  

Katherine Banwell:

If we look at care and treatment, why should a patient with myelofibrosis consider a second opinion with a specialist?  

Dr. Idoroenyi Amanam:

The field is rapidly changing, and we have very few FDA-approved therapies even in 2024 for myeloproliferative disorders and myelofibrosis. And because of some of the changes in understanding of the biology of this disease, I think that there are many patients that will benefit from physician or a center that specializes in treating patients with this very rare disorder. And I believe that   even though we have very few FDA-approved therapies, I do believe that we can give patients an opportunity to get this type of disorder under control, and actually offer curative approaches that may not be available to all facilities. 

Recent Advances in Myelofibrosis Research | Disease-Modifying Therapies

Where is progress being made in the field of myelofibrosis? Dr. Idoroenyi Amanam discusses how disease-modifying therapies and cellular therapies are advancing patient care.

Dr. Idoroenyi Amanam is a specialist in myeloproliferative disorders and is an Assistant Professor in the Division of Leukemia at City of Hope. Learn more about Dr. Amanam.

Download Resource Guide

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Expert Perspective | A Concerted Effort to Advance Myelofibrosis Care

Myelofibrosis Therapies in Clinical Trials | BET Inhibitors

Myelofibrosis Therapies in Clinical Trials | BET Inhibitors 

Transcript:

Katherine Banwell:

What are your areas of focus in myelofibrosis research? 

Dr. Idoroenyi Amanam:

So, I think the way that I would break it down, when you think about myelofibrosis patients, or patients with myeloproliferative disorders, patients who are diagnosed, and they’re really pretty much asymptomatic, and then you have patients who have some symptoms, then you have some patients who are very symptomatic or transitioning into a more severe disease and predominantly, that disease is acute leukemia. And so, I have an interest in trying to identify new treatments for all of these types of patients.  

Katherine Banwell:

In your opinion, what new myelofibrosis advances are most promising? 

Dr. Idoroenyi Amanam:

So, traditionally, for a lot of myeloproliferative disorders, including myelofibrosis, we had a watch and wait approach, so we typically actually did not really have very good therapies. And I think all of that changed with the approval of the first JAK inhibitor, ruxolitinib (Jakafi).  

And we have transitioned to understanding the signaling pathways that are involved in myelofibrosis and myeloproliferative disorders. And we understand certain driver mutations that are involved in these signaling pathways and involved in other areas that help drive these diseases.  

And I think what’s exciting for us right now is, we’re transitioning from having a Band-Aid approach, or a watching and wait approach, to actually having interventions that are what I would call disease-modifying drugs. And so, these drugs target some of these drivers that drive the disease.  

They target some of the inflammation that’s associated with the disease, and, in fact, they’re also targeting some of our own immune cells that may help us protect us against these diseases progressing into more aggressive disorders. 

Katherine Banwell:

How are innovations in technology accelerating myelofibrosis research?  

Dr. Idoroenyi Amanam:

You think about how we understood these diseases 20 to 30 years ago. I think we understood the clinical presentation. We understood that some patients had big spleens, we understood that those patients’ counts didn’t do so well, we understood when we would look at their marrow, how the cells looked under the microscope. And we’ve transitioned to now understanding how some of those proteins that are   in these  signaling pathways are either turned on or turned off.    

We have a better understanding of the genetics of this disease, and how it changes over time, and what that means for patients prognostically, and how they will actually respond to our current therapies.  

And obviously, it’s driving how we are setting up clinical trials and other therapies  for the future. And so, I really would say our  genetic, genomic understanding of these disorders have really opened up many opportunities for us to treat these patients better.  

Katherine Banwell:

Well, are there other research developments showing promise that patients should know about? 

Dr. Idoroenyi Amanam:

So, traditionally, we’ve thought about  these disorders as disorders where, maybe if we improved symptoms – so we give you, maybe, a pill that would help with your symptoms, or we’ll give you another medication that will help with keeping your counts under control or reducing your risk for clotting and stroke.  

And we are currently in a space where cellular therapy has exploded across all areas of oncology. We have many clinical trials that are using  therapies that  take your own cells,  or other donor cells from healthy  people, and we are giving them to patients with the hope that it will  get rid of these  bad cells that are driving myelofibrosis.  

Expert Perspective | A Concerted Effort to Advance Myelofibrosis Care

 

Dr. John Mascarenhas discusses the evolving landscape of myelofibrosis research, emphasizing the concerted effort among researchers, pharmaceutical companies, and advocacy organizations to advance care and treatment options for patients.

Dr. John Mascarenhas is Professor of Medicine at the Icahn School of Medicine at Mount Sinai (ISMMS) and the Director of the Adult Leukemia Program and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders at Mount Sinai. Learn more about Dr. Mascarenhas.

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Is Stem Cell Transplant the Only Curative Option for Myelofibrosis?

Is Stem Cell Transplant the Only Curative Option for Myelofibrosis?

Transcript:

Katherine Banwell:

Is there anything you’d like to add about the evolution of myelofibrosis care? What are you excited about?  

Dr. John Mascarenhas:

I always make the comment they don’t feel rare to me because I see so many patients with myelofibrosis, and it’s what I do. But I recognize in the context of lung cancer, breast cancer, other more common cancers, these can be forgotten diseases. But what has been encouraging is, between the NIH funding, for example, our research consortium, which is really geared to translating the biology into clinical trials across the country.  

Pharmaceutical interest, which is essential to providing drugs and finance to run trials. Young investigators that are coming to the field that want to make a difference, institutions that continue to support the programs, and then foundations. Whether it’s MPN Research Foundation, Leukemia & Lymphoma Society, it really takes a village. And we’ve been working with the FDA to try to better understand how to develop trials that are meaningful that can get drugs approved and to the patients. 

So, it’s a concerted effort, and I’ve been enthusiastic. I remain optimistic that everyone is trying to do the same thing, achieve the same goal, and work together, and that’s the only way we’re going to be able to do it. 

Katherine Banwell:

Yeah. How long does it take for the FDA to approve a drug? 

Dr. John Mascarenhas:

Forever. It feels like forever. It’s a long process, and for patients, it can be quite frustrating, because there’s so many steps involved. From just the original, initial steps to allow you to introduce a drug into humans, there are IND-enabling studies, so there’s a lot that goes into this.  

And then the initial studies are safety studies. They often can take quite some time. There’s a lot of scrutiny on safety, obviously, because the FDA is really charging to making sure that we do no harm, that we maintain safety for patients, so that can take a long time. And then the ultimate testing and comparison to a control arm is essential to get a drug approved. 

So, we’re looking at a timeline that can easily be a decade from the time we have a great idea, and have a drug available to us, to the time that we can prove that through the different stages, and then demonstrate that to the FDA and negotiate what a label will look like. And that is both a time-consuming process, a very expensive process, and a laborious process, but obviously an important process. 

Katherine Banwell:

Yes, and as you say, so many new drugs and therapies have become available in the last 10 years or more that really have advanced myelofibrosis care enormously. 

How Can You Learn More About Myelofibrosis Clinical Trials?

 

Dr. John Mascarenhas shares advice for patients looking to learn more about clinical trials starting with consulting a specialist. Dr. Mascarenhas also emphasizes key questions to ask, including a discussion of the benefits versus risks of participating in a potential trial. 

Dr. John Mascarenhas is Professor of Medicine at the Icahn School of Medicine at Mount Sinai (ISMMS) and the Director of the Adult Leukemia Program and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders at Mount Sinai. Learn more about Dr. Mascarenhas.

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Transcript:

Katherine Banwell:

What about clinical trials? How can patients learn more? 

Dr. John Mascarenhas:

Well, clinical trials is definitely a confusing area because there are many clinical trials, and some of them are relevant to some patients may be not relevant to other patients.  

So, I think two ways is, see someone who does this. So, not everyone has as their primary care provider hematologist an expert, or someone who’s dedicated to doing this. They may be in a practice where they’re in the community setting; it’s not reasonable for them to be seen at a tertiary care center. 

But if you can get there even for a consultation or an initial visit to get plugged in, I think it’s really critical to see someone who is really invested in this with research opportunities, and clinical trial availabilities. And then the other resource would be clinicaltrials.gov.  

You can go in there, you can put in your diagnosis myelofibrosis. You can even manipulate it for geography to understand what trials are in your area. 

But it is a good way of looking, just to understand what’s there. And then the MPN Research Foundation, which is very supportive of the patient community and engages them, is often a very good resource to go to, to either learn about trials or join webinars where physicians that do this will discuss, and I think that’s another excellent resource. 

Katherine Banwell:

What questions should patients ask their team about clinical trials?   

Dr. John Mascarenhas:

Well, are there clinical trials for what I have? Because again, they can be very particular to where you are in the disease process, what medications you are on, what your kidney function is, things that may really influence decision-making. So, are there clinical trials, what are the clinical trials evaluating, what should I expect from them, both potentially from a positive angle, but also from a negative. What are the known toxicities, what would be the time commitment? Trials are more involved, and they’re more involved for a reason. 

I actually personally think patients do better on clinical trials than standard of care. The reason why I think that is because they are more involved. There’s a lot more oversight and eyes on you. Not just a physician perspective, but maybe more importantly, from a research nurse and research coordinator perspective. There’s a lot of regulatory burden which translates, I think, to a lot of attention to safety and assessment for advocacy.  

So, I think understanding what that looks like at any given institution, and how it will affect the patient and their caregivers from a time perspective, and obviously toxicity. But also, what is this trial trying to achieve? Does it make sense for what I’m trying to achieve? 

Katherine Banwell:

I suppose another question might be where this trial is taking place? As a myelofibrosis patient and a caregiver, are we going to have to travel to get to this clinical trial? 

Dr. John Mascarenhas:

I think that’s a major obstacle for a lot of patients. We’re talking about a disease that typically affects people that are in there sixth, seventh, eighth decade of life. Patients don’t all live, as I’ve said, right around a cancer center or a tertiary care center, so travel, the logistics of it, the ability to have that support available. Sometimes it’s loved ones, and adult children having to take time off of work to be able to help in that process.  

It’s a lot, and I’m particularly sensitive to it, because I work in a metropolitan area, and I realize getting in and out is not easy. And a lot of times, these trials understand that, and they build into the trials stipends and support for transportation and/or lodging which helps. It’s not perfect, but it can help at least financially, and sometimes logistically, so I would definitely inquire about what those resources are.  

And sometimes foundations also help bridge the gaps for patients to help link them to trials and facilitate that. So, it’s a super important part of engaging in a trial. 

Katherine Banwell:

And who is on the health care team that might be able to answer questions like this? 

Dr. John Mascarenhas:

Well, for sure, the physician should be able to. But I think the most valuable resource often is the nurse and the nurse practitioner. There are usually research coordinators. These are often young people, but very bright young people, that are very invested in this that will sometimes show up at the clinic to talk to the patient or will be a phone resource that you could reach out to. So, it can really be, I think, three levels. The coordinator, the nurse or nurse practitioner, or physician assistant, and the physician. So, it really shouldn’t be one person, but a team of people that are available to you. 

Expert Outlook | New Myelofibrosis Therapies Showing Promise

 

What myelofibrosis therapies in development show promise? Dr. John Mascarenhas, a myelofibrosis researcher, reviews innovative treatments that are being combined with JAK inhibitors as well as single agent therapies that are making headway for patients with myelofibrosis. 

Dr. John Mascarenhas is Professor of Medicine at the Icahn School of Medicine at Mount Sinai (ISMMS) and the Director of the Adult Leukemia Program and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders at Mount Sinai. Learn more about Dr. Mascarenhas.

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Evolving Myelofibrosis Treatment Options: What You Should Know

Expert Perspective | A Concerted Effort to Advance Myelofibrosis Care

Expert Perspective | A Concerted Effort to Advance Myelofibrosis Care

Transcript:

Katherine Banwell:

The JAK inhibitor class of therapies has been around for over a decade now. What new therapies are showing promise when being studied in combination with these therapies? 

Dr. John Mascarenhas:

So, I think the ones that are really exciting, and there are a number. We don’t know which one is the best, but I’ll tell you the ones that I think really have potential would be drugs like pelabresib, the pan-BET inhibitor, and the MANIFEST-2 study. Even a drug called navitoclax, that isn’t going to move forward, taught us a lot. We know that pathway is important, we just have to improve upon how we’re doing this.

Drugs like selinexor (Xpovio), the XPO1 inhibitor, is ongoing in the SENTRY study. A drug called navtemadlin is a very active drug, and that’s been shown as a single agent after ruxolitinib (Jakafi) failure. But now, it’s going after those patients who are not having an optimal response with ruxolitinib, adding it on on the backend.  

So, what I really love about the way we’re doing this is, I think it’s a very thoughtful approach trying to use these really active drugs that exploit non-redundant pathways in the disease, both either up front, to really get the biggest bang for your buck, to really try to reduce the diseased burden earlier on, or to try to add on as a strategy if patients aren’t enjoying the maximum benefit from ruxolitinib. So, we are really trying to tackle it from different angles and some of these drugs really look promising. 

Katherine Banwell:

Yeah, yeah. Are there other single agent therapies that are being studied for myelofibrosis?  

Dr. John Mascarenhas:

There are. So, I’ll name two that I also think really deserve some attention. One is called TP-3654, and it’s a drug by Sumitomo that’s a PIM 1 kinase inhibitor. So, this also goes after a very specific pathway – inflammatory pathway – a signaling pathway – that is known to be an important driver of disease and has very nice data, particularly from a symptom-burden perspective. But also, again, this concept of disease modulation and reduction in cytokines in patients who’ve previously been on ruxolitinib.  

So, there’s data there where they’re going to add it on to ruxolitinib that really looks like an interesting approach forward. And then the drug I think many of us are very anxious to see results in which is ongoing, is the IMpactMF study.   

This is the randomized phase three study of imetelstat (Rytelo), which is a telomerase inhibitor and infusional agent that goes after a very important enzyme that keeps malignant cells alive and really is one of the drugs that I think has the true potential to go after the stem cell, the origin of the disease, and improve survival. It’s the only study we have had, and currently have, where the endpoint for the registration phase we’ve studied is survival. It’s patients who have failed ruxolitinib and are getting this drug as a single agent, versus best available therapy.  

A very exciting trial and really important. Whether you’re on the trial or you’re a candidate for it, it really helps us move the field forward, because it gives us essential insights into the disease and how to do better. 

Katherine Banwell:

Yeah. When it comes to the latest research and treatment, what question should patients ask their health care team about new or developing treatment options? 

 Dr. John Mascarenhas:

Well, I think every patient is different, and truly different since their biology is different, the way they present is different, their course is different. So, really, the treatment options, including the trial options, really need to be tailored to the patient. It has to make sense for that patient. It has to meet their expectations, be aligned with their goals of therapy, and balance. Balance risk with potential benefit. Patients have to understand. The physicians have to present very clearly that some trials are randomized studies, and you could get a placebo. 

And it’s often blinded, so the patient doesn’t know, the physician doesn’t know. But importantly, in some of these studies, there’s crossovers, so even if you don’t get the drug up front, you can get it in the backend. All of these things really have to be disclosed very carefully and thoughtfully, so the patient’s really making an informed decision that makes sense for them and is meeting their expectations. 

Updates in Myelofibrosis Research From an Expert

 
Dr. John Mascarenhas shares updates on myelofibrosis research. Dr. Mascarenhas highlights the shift towards combination therapies, particularly the use of JAK inhibitors alongside novel agents, with the goal of improving disease response and patient outcomes.
 
Dr. John Mascarenhas is Professor of Medicine at the Icahn School of Medicine at Mount Sinai (ISMMS) and the Director of the Adult Leukemia Program and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders at Mount Sinai. Learn more about Dr. Mascarenhas.

See More from Evolve Myelofibrosis

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Expert Outlook | New Myelofibrosis Therapies Showing Promise

Expert Outlook | New Myelofibrosis Therapies Showing Promise

How Can You Learn More About Myelofibrosis Clinical Trials?

How Can You Learn More About Myelofibrosis Clinical Trials?

Expert Perspective | A Concerted Effort to Advance Myelofibrosis Care

Expert Perspective | A Concerted Effort to Advance Myelofibrosis Care

Transcript:

Dr. John Mascarenhas:

My name is John Mascarenhas, I am a professor of medicine at the Icahn School of Medicine here in New York City. I direct the Center of Excellence for Blood Cancers and Myeloid Disorders, and I lead the adult leukemia program. But my real passion and interest is in myeloproliferative neoplasms and translational research, trying to understand the biology of the diseases and helping translate that into effective therapies in the clinic. 

Katherine Banwell:

Dr. Mascarenhas, from your perspective, what are the highlights so far this year in myelofibrosis research? 

Dr. John Mascarenhas:

So, I think myelofibrosis research – I’ve been in this field for about 20 years, and I’ve watched it go from a field where we had very little insight into the biology of the disease, which meant very little targeted or informed therapies to the era of JAK inhibitors.  

The first being 2011 with ruxolitinib (Jakafi), then 2019 with fedratinib, 2022 with pacritinib, and then 2023 with momelotinib (Inrebic), has really afforded us a significant advantage in trying to tailor the treatments for different patient niches to improve spleen and symptom benefit.  

And I do think that translates to a survival benefit in our patients with myelofibrosis. So, outside of bone marrow transplant, really these treatments are not curing patients, but they are addressing certain aspects of the disease. 

What I’m most excited about is the new era; the next generation of approaches that we’re seeing, and we have been seeing, and will continue to see emerge, and these include combination therapy approaches up front. So, taking those JAK inhibitors, the benefit they have, and trying to improve upon that with the addition of informed therapies, rational drugs that have pre-clinical evidence. 

Meaning, in the lab with cells from patients with animals that are engineered to have myelofibrosis, so that when we take them into the clinic, we are more confident, more informed in our decision-making, that we’re not exposing patients to drugs that really don’t have rationale.

Katherine Banwell:

What do these research advances mean for myelofibrosis patients? 

Dr. John Mascarenhas:

Well, I think what we’re seeing is a shift towards more combination therapy. So, what I think it means for a patient is deeper responses from not just spleen and symptom, but what we’re looking at very intently are biomarkers of disease modulation and disease response, hopefully, disease course changes.  

So, things like reductions in their driver mutation. These are gene mutations like JAK2, CALR, MPL, reductions in inflammatory markers, reduction in bone marrow fibrosis in the bone marrow.  

All of these things suggest that we’re really starting to modulate the disease in a more significant way. What we’re trying to show is that that actually matters to a patient, that these findings actually translate to better progression-free survival, better overall survival. So, I’m really enthusiastic and excited by what is happening now, because I do think it pays off. 

It’s incremental benefits, but things that are now more targeted, like mutant CALR antibody approaches, or BiTE approaches.  

To those patients who have this abnormal CALR protein expressed on the surface of the cell transformative with at least the potential to be JAK2 selective inhibitors, really going after that mutant JAK2 in a very selective way, or a Type II JAK2 inhibitor. Really, the potential to have very molecularly defined targeted therapies that will, hopefully, get us much deeper responses; that patients will see even greater benefits, better improvements in symptom burden, spleen, but ultimately survival.  

Dr. Akriti Jain: Why Is It Important for You to Empower Patients?

 

Why is it important to empower patients? Expert Dr. Akriti Jain from Cleveland Clinic discusses her methods of educating and empowering her patients and how empowerment sets patients on their path to optimal cancer care.
 

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Kimberly Smith: Why Is It Important for You to Empower Patients?

Kimberly Smith: Why Is It Important for You to Empower Patients?


Transcript:

Dr. Akriti Jain:

Empowering my patients is very important to me because I want to make sure when a patient leaves my clinic appointment they have a basic understanding of the disease that we’re fighting together. I try to explain to them basic understanding of how a bone marrow functions, where it is present, it’s in their long bones, and then draw them a chicken scratch of what MDS is and what MPN is, what a myeloproliferative neoplasm actually entails, how it is diagnosed, print them out their bone marrow biopsy reports so that they understand where the pathologist is seeing the issues.

And this is, again, very important because if a patient understands what they’re fighting, what we’re fighting together, they’re more likely to pay attention, they’re more likely to be more compliant, they’re more likely to adhere to what you recommend, get those lab tests, come to their visits, take the medications, and call you if they have concerns or questions.

Emotional Health | Why It’s Vital for Myelofibrosis Patients to Share Concerns

Why is it crucial for myelofibrosis patients to discuss their emotional concerns with their care team? Dr. Naveen Pemmaraju explains how managing anxiety and fear is essential to maintaining overall well-being. 

Dr. Naveen Pemmaraju is Director of the Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Program and Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Pemmaraju.

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Advice for Shared Decision-Making | Myelofibrosis Care and Treatment Goals

Myelofibrosis Symptoms and Side Effects | Why Speaking Up Is Vital

Myelofibrosis Symptoms and Side Effects | Why Speaking Up Is Vital

Transcript:

Katherine Banwell:

Managing the worry associated with a diagnosis or concerns about the future, and we did touch upon that earlier, it can lead to anxiety and fear. Why is it important for patients to share any worries they may be having with their care team?  

Dr. Naveen Pemmaraju:

Well, I love this question. It really wraps up everything we’re talking about here. I believe that part of the journey for the patient does include mental and psychological safety. So, it’s very difficult to make major life decisions when one is not feeling mentally, or psychologically safe. So, that’s what you’re hitting on here. Anxiety, fear, and worry, of course, are a natural and important part of the patient journey with any cancer, much less a rare cancer and blood cancer on top of that. However, sometimes in some patients, it can become so paralyzing, so overtaking, and overwhelming that it may prevent the ability of the patient to receive information, process it, and then make a decision back. Yes, we want people to have caregivers, and power of attorney, all those things are essential, but we also want people to have their own agency in aegis.  

So, I would approach this from three aspects. I really love this question because I don’t think we were addressing it head-on 10 or 15 years ago. One aspect is the disease itself. These MPNs, systemic mastocytosis, eosinophilia, myelofibrosis, PV, ET, all of these MPNs can secrete these cytokines and granules that can mess up the patient’s mindset, even just profound fatigue leading to a slowing down of the neurological process. So, I think underlying control of the disease is something that can affect this. Number two is the side effects from some of these medicines. Interferon is a great example, a wonderful class of drugs that’s been around for decades, treated for solid and liquid tumors, but it has a known side effect of causing brain fog. Some of these issues can even cause depression and anxiety in some people. So, education, mitigation, following these things with dose reduction, that’s an important part.  

A third aspect, Katherine, is actually looking with a counselor and a therapist on the spectrum of this. So, normal, adjustment disorder, depression, for example. What we’ve had as a breakthrough at our center has been the supportive palliative care team. They’ve been phenomenal. So, this is a group of doctors who’s kind of one-third internist, one-third oncologist, and one-third psychiatry support.  

So, rather than the usual consults that we used to do either to psychiatry or to social work case managers, there is this burgeoning field of supportive care medicine which has revolutionized the care, I think, particularly for solid tumor patients and now hopefully for our blood cancer patients. So, I’m able to refer patients for a variety of reasons. There’s a fatigue clinic for overwhelming fatigue. There is obviously depression, and anxiety support, either with medications, talk therapy, or both. Smoking secession for folks who are still smoking and maybe either withdrawing or quitting is causing stress.  

So, it’s a really cool science and if your center has that, that’s something to inquire about. Then lastly, as we mentioned, a nice running theme today, Katherine, is looking for other medical stuff outside of the MPN. I mentioned thyroid earlier. Remember, you have a thyroid abnormality that can cause fatigue, depression, and anxiety, right? So, what’s your TSH thyroid function, and vitamin deficiencies?  

Screening for your other well-person screening exams, looking for solid tumors, looking for other conditions that may be mimicking the MPN, or mimicking one of your other aspects. So, again, it comes down to partnership with the primary care team and looking at that. So, I think those are some of the aspects that I want to mention, but it’s such an important part of the journey. I really have to mention that as well. 

Myelofibrosis Care | Impact of Diet & Lifestyle Modifications

Can diet and lifestyle help manage myelofibrosis symptoms? Dr. Pemmaraju explains how the Mediterranean diet and practices like yoga may improve quality of life for patients. 

Dr. Naveen Pemmaraju is Director of the Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Program and Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Pemmaraju.

Download Resource Guide

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Advice for Shared Decision-Making | Myelofibrosis Care and Treatment Goals

Transcript:

Katherine Banwell:

“Can diet play a role in either manifesting the disease and or helping with healing? Also, how important is exercise to the healing?”  

Dr. Naveen Pemmaraju:

I give a lot of credit to this area, to my colleagues, Ruben Mesa, Dr. Angela Fleischman, and Dr. Robyn Scherber. A lot of data that’s come out of these groups, which has shown two major findings in our MPN patients of potential clinical significance. One is as the questioner is asking about diet. It is true that we’re, several studies are pointing towards the anti-inflammatory Mediterranean diet as a potential benefit to our patients with MPN. Lots of different ideas there when they measure cytokines. 

These abnormal protein signatures that are in MPN patients can cause fatigue and some of the bad quality of life can be dramatically improved in some cases by following a strict Mediterranean diet over weeks and months. So, that’s something important. People should check it out. Obviously, diets have to be addressed with each patient and each provider because sometimes a diet may work for someone and not for you because of comorbidities, vitamin deficiencies, electrolytes, etc.  

Then the second aspect, if I may include in this question, is also the concept of yoga/meditation. Dr. Ruben Mesa and others have shown, the same thing, that you can have a potential downregulation of some of these abnormal cytokines. However, the caveat is it must be done right with a guided trainer in a real program over a certain period of time. What I think both of these non-pharmacological interventions tell us is that there are things beyond medicines and pills that may really help our patients in some aspect of the disease.  

Well, if that aspect is fatigue, night sweats, headaches, I think that’s a really important thing. So, let’s say together on this program that these data sets are evolving, they’re interesting, they’re intriguing. For some people, it may be an easy incorporation. Frankly, some people may already be doing these things, but as you ask nicely, let’s include in the discussion non-pharmacologic as we heavily investigate the pharmacologic as well. We’re all open to that. Let’s see the data, and the data is evolving.   

When Should Myelofibrosis Mutational Testing Be Repeated?

When should myelofibrosis mutational testing be repeated? Dr. Pemmaraju discusses the importance of retesting at key points and how mutations impact care and treatment plans. 

Dr. Naveen Pemmaraju is Director of the Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Program and Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Pemmaraju.

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Myelofibrosis Care | The Impact of Test Results

Transcript:

Katherine Banwell:

“I understand that mutational testing should be done at diagnosis. Is there a point where there would be a need to repeat this test?”  

Dr. Naveen Pemmaraju:

Oh, that’s an awesome question. So, we were mentioning that earlier. I do believe and I advocate that all patients should have molecular testing, particularly now as it’s more available widely before it wasn’t. Again, we level set what we’re talking about. In myelofibrosis, three common driver mutations, JAK2, CALR, MPL makes up about 90 percent. 

Then in addition to that, there’s the triple-negative, and you usually find an additional mutation. Then on top of these big three, it’s common to have co-mutations, ASXL1, etc. What we found in this MIPSS score that we just mentioned ties into that. We found now that for the first time, we can incorporate these molecular findings to prognosticate for the patients. That’s why it’s important to check them. So, to this question by Joel, yes, if you have access and availability, not only checking it at baseline but later on at a provoking event.  

So, at the time of relapse, progression, going onto a clinical trial, just to name three of several. I think it’s a good idea to recheck the molecular status. The problem and barriers are what you would expect, cost, expense, access, availability, justification, etc., etc. So, it’s not a mandatory part of the field, especially in the standard of care, non-research aspect. However, if we can get to the point where we can do that, it would be nice and helpful because these mutations change, they’re dynamic.   

You can have negative for mutation at baseline, positive, and even vice versa, depending on therapies. Are you going to go for a transplant? Are you going to go to a clinical trial? Are you changing therapy? It would be nice to know. 

How Are Prognostic Scoring Systems Used in Myelofibrosis Care?

How are scoring systems such as DIPSS used in myelofibrosis care? Dr. Pemmaraju explains how these tools assess myelofibrosis prognosis and guide treatment decisions. 

Dr. Naveen Pemmaraju is Director of the Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Program and Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Pemmaraju.

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Myelofibrosis Care | The Impact of Test Results

Myelofibrosis Care | The Impact of Test Results

Transcript:

Katherine Banwell:

“Can you explain the dynamic international prognostic scoring system or DIPSS?” Thank goodness there’s an acronym for that.  

Dr. Naveen Pemmaraju:

Yeah, no, it’s a great question, scoring systems, right?  

Katherine Banwell:

Yeah, and Cliff wants to know how he can ask his doctor about it.  

Dr. Naveen Pemmaraju:

Right, so the easiest way to talk about it, the good news is everything we’ve been talking about is incorporated in the scoring system. So, said in another way, we’ve been talking about it subjectively, the scoring systems try to make the subject objective. So, quick history, these started in 2009 with the IPSS, International Prognostic Scoring System. The concept there were a thousand patients in Europe and basically trying to observe the natural history of the progression of myelofibrosis. This was just before, just as the JAK inhibitor era was starting. What we found is that the four groups nicely separate.  

So, the lowest of the low-risk group potentially can be measured in decades for overall survival. Intermediate one, intermediate two, and high risk, again, all separated by overall survival and AML leukemia transformation risk. Now, that’s evolved over time as the questioner is asking for more sophisticated scoring systems. So, that’s all you need to know. So, DIPSS Plus just means Dynamic International Prognostic Scoring System.  

Then there’s DIPSS plus, and can you believe it? There’s even the MIPSS now, the Molecular International Prognostic Scoring System. All right. So, at least there’s a rhyme and reason there. I think each iteration is telling you that we are dynamically understanding more about the disease. Two, the IPSS, the original one, was meant to be only at diagnosis, and the DIPSS by definition, dynamic scoring, is any time during the course of the disease, that’s interesting. Then three, they’re incorporating new factors each time.   

So, from the time of the IPSS to the DIPSS and now the MIPSS, you’re incorporating all these factors that we couldn’t before. Cytogenetics, molecular findings, anemia, transfusion, burn, thrombocytopenia, etc. So, that’s basically it. You can ask your doctor. I mean, basically, in the course of what we do in the non-clinical trial standard of care, even if somebody doesn’t hand stop and calculate these risk scores, we’re talking about the same thing, right? The subjective or the objective matchup.  

However, of interest to the patients, there are calculators that are available, you know, obviously rather than doing it in isolation in your house. Yes, it is better, I agree to do it with your doctor, with your provider team, and see what it means for you. The goal of these is twofold. In clinical trials to help stratify patients so you can understand who’s high risk versus lower. However, in the standard of care, sure it may help with transplant decisions, referrals for clinical trials, etc. 

Myelofibrosis Symptoms and Side Effects | Why Speaking Up Is Vital

Dr. Naveen Pemmaraju emphasizes the importance of knowing your body and sharing all myelofibrosis symptoms and side effects with their healthcare team. 

Dr. Naveen Pemmaraju is Director of the Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Program and Professor 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:

So, the symptoms of myelofibrosis as well as the side effects of certain medications can vary greatly among patients. 

Dr. Naveen Pemmaraju:

Yeah. 

Katherine Banwell:

Why is it critical for patients to share any issues they may be having with their care team?  

Dr. Naveen Pemmaraju:

Yeah, exactly what you said. So, those two concepts are tied. Since the disease is so rare and it’s so heterogeneous, not just patient to patient, but within the same patient over the journey of years, that is the reason. So, because of that, that’s why one has to communicate every single thing to the healthcare team. It’s interesting. Something that the patient may not believe is serious, the caregiver sometimes knows, right, team?  

So, sometimes the person who’s your loved one or caregiver, “Oh, you know, that’s not-quite-right.” Sometimes the patient knows obviously, and then sometimes the healthcare team may say, “You know, that’s not-quite-right.” I think the not-quite-right thing is the key because that is what supersedes or at least precedes lab testing, X-rays, imaging, and bone marrows, it has to be some provocation. So, what I try to tell people is you know your body best. So, you want to be in touch with yourself, with your body, and anything that isn’t right, don’t be the final judge on that.  

Push it up the chain, let your caregiver know, let your doctors know, let your team know, and let them help you decide. Sometimes it may be nothing, that’s fine. Sometimes it may be something. Sometimes it may be something outside of your MPN. That’s another key theme, I think, I mentioned here a couple of times. Anemia is a good example. So, lowering of the hemoglobin. It’s exactly what you just asked me. So, in addition to looking to see if it’s the disease progression itself, okay, fine.  

However, could it also be drug toxicities, as you mentioned? So, the JAK inhibitor may be causing the anemia or whatever. Then the third bucket is, could it be anemia of regular life stuff, iron deficiency anemia. Could it be a colon cancer or a polyp that’s hiding there? Could it be vitamin B12 deficiency, hemolysis, immune, or something destroying the red blood cells, etc., etc.? So, you make an awesome point, which is all of that can be alleviated or the ball can be started rolling, if you will, by mentioning it. So, the key is no shame, no silence, and mention everything.  

Katherine Banwell:

No silly questions.  

Dr. Naveen Pemmaraju:

No silly questions, that’s right.  

Emerging Treatments in Myelofibrosis Care

Dr. Naveen Pemmaraju from MD Anderson Cancer Center discusses emerging myelofibrosis therapies currently in Phase II and III trials, including novel agents and combination treatments that show promise for patients. 

Dr. Naveen Pemmaraju is Director of the Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Program and Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Pemmaraju.

Download Resource Guide

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Advice for Shared Decision-Making | Myelofibrosis Care and Treatment Goals

Advice for Shared Decision-Making | Myelofibrosis Care and Treatment Goals

What Myelofibrosis Treatment Types Are Available?

What Myelofibrosis Treatment Types Are Available?

Transcript:

Katherine Banwell:

There are a couple of new and emerging treatments as well, right? What are those?  

Dr. Naveen Pemmaraju:

Yeah, so right. So, I’m proud to report to the viewers that just now in real time, just in the last year, really we have had several major developments. Now these are not yet FDA-approved agents. They’re experimental investigational agents, but they’ve reached what’s called Phase II or Phase III testing which are the later stages of testing. I’d like to highlight four or five of those.  

These are mostly in the combination space. So, this is a JAK inhibitor plus the new agent. One is called navitoclax. That’s a BCLXL inhibitor, not yet FDA-approved for any indication. However, this has been shown to have activity in the Phase I and II trials, either as a single agent or in combination.  

Now that’s reached Phase III testing. The second one is the pelabresib agent, which is a bromodomain or BET inhibitor. A third, if you can believe it, it’s selinexor (Xpovio), which is an XPO1 inhibitor. Also, a fourth really now entering into Phase III trials is the MDM2 inhibitor navtemadlin. You have these four drugs, which are either completing or starting Phase III, which is the most advanced testing.  

That means they’re randomized trials, usually international trials, many hundreds of patients. It’s an amazing effort that’s unprecedented. By the way, these are being tested in the frontline setting before patients have ever had a JAK inhibitor in combination with.

Beyond that, Katherine, there’s many, many trials with novel agents by themselves. So, imetelstat (Rytelo) comes to mind, which is a telomerase inhibitor, for example, which is also in Phase III testing in the relapse setting. So, you’ve already had a JAK inhibitor, it didn’t work out for you. Interestingly in that trial, the overall survival is the primary endpoint rather than spleen and symptoms, which marks the first time we’ve ever seen that. 

It also marks the understanding that these chronic diseases, chronic myelofibrosis can then turn into a more advanced acute in the relapse setting. So, that’s just a sample of some of the ones that are now entering the late stages of trials, many more in Phase I and II. In a good way, there’s a new trial opening once a week.