Tag Archive for: myelofibrosis treatment

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.

See More from Evolve Myelofibrosis

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Updates in Myelofibrosis Research From an Expert

Updates in Myelofibrosis Research From an Expert

How Can You Learn More About Myelofibrosis Clinical Trials?

How Can You Learn More About Myelofibrosis Clinical Trials?

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.

See More from Evolve Myelofibrosis

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Myelofibrosis Clinical Trial Participation | How Does It Move Research Forward

Myelofibrosis Clinical Trial Participation | How Does It Move Research Forward?

Considering a Myelofibrosis Clinical Trial? Questions You Should Ask

Considering a Myelofibrosis Clinical Trial? Questions You Should Ask

Expert Perspective | A Concerted Effort to Advance Myelofibrosis Care

Expert Perspective | A Concerted Effort to Advance Myelofibrosis Care

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. 

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.  

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

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.

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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. 

What Myelofibrosis Treatment Types Are Available?

Dr. Naveen Pemmaraju outlines available myelofibrosis therapies, such as JAK inhibitors, and discusses the role of clinical trials and emerging treatments for managing the disease.  

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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Emerging Treatments in Myelofibrosis Care

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Myelofibrosis Care | The Impact of Test Results

Myelofibrosis Care | The Impact of Test Results

Transcript:

Katherine Banwell:

So, once all testing is complete and the patient has an accurate diagnosis, they’ll work with their doctor then on a treatment approach. You’ve touched on this a little bit, but  

What are the types of treatment available for people with myelofibrosis? 

Dr. Naveen Pemmaraju:

Yeah, thanks, Katherine. We’ll keep it general and standard of care. As you mentioned at the top, I’ll reiterate, that none of these are intended to be specific instructions for specific folks. However, in general, for the category of patients with myelofibrosis, in general, there’s not many treatments, unfortunately. As of 2024, we have only four standard JAK inhibitors. So, that’s this pathway we’re talking about, JAK-STAT. Interestingly, you don’t have to be JAK2V617F mutated. These are for the whole pathway.  

So, all patients with myelofibrosis, are intermediate to high risk. The first one, Katherine, is ruxolitinib (Jakafi), which has been around for more than a decade, and first in class JAK inhibitor. The second drug is fedratinib (Inrebic). The third is pacritinib (Vonjo), approved only in 2020 for those patients with less than platelets of 50. Then the myelofibrosis drug, momelotinib (Ojjaara), just approved not even a year ago, in September of 2023 for myelofibrosis with anemia. So, those four are considered as called JAK inhibitors.  

They are really the only targeted therapy class of drugs specifically approved in the MF space. Outside of that, there’s older and other drugs that me and others have used, if you will, so-called off-label or historical use, hydroxyurea  (Hydrea), interferon products such as pegylated interferon. Hypomethylators such as azacitidine (Vidaza) and decitabine (Dacogen), particularly in more advanced cases. Some of those drugs are borrowed from MDS and AML and have been around for decades.  

Then of course, finally, clinical trials. We really recommend folks, if they have the ability and feasibility, clinical trials, even in the first diagnosis setting. So, untreated, first therapy. These clinical trials, Katherine, are based on three factors. One is JAK inhibitor plus another agent. So, that’s kind of like a combination trial. Two is add-on agents. So, you’re already on the JAK inhibitor for a while, maybe it’s starting to not work. Then you add in a third agent.  

Then three is a completely novel agent beyond the JAK-STAT pathway. Then maybe we can even add a fourth one now as this is evolving in real-time, which is anemia-targeting drugs. Many of our patients have either transfusion-dependent or bad anemia. Some of the drugs that are being developed are specifically aimed at them. 

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

Myelofibrosis expert Dr. Naveen Pemmaraju advises on how patients and healthcare teams can partner together by communicating care goals and exploring treatment options.

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

Transcript:

Katherine Banwell:

When it comes to choosing therapy, Dr. Pemmaraju, it’s important to work with your healthcare team to identify what is going to work best for you. So, as a clinician, how do you define shared decision-making?  

Dr. Naveen Pemmaraju:

Very important. So, shared decision-making to me means a partnership. It means a journey that the patient and the providing team are about to embark on. It’s a very different approach than a one-way, I tell you, you do this. Instead, I see it as a bi-directional exchange of ideas.  

Each visit, each EPIC in-basket or EMR communication, each touch with the healthcare system, the pharmacist, the PA, nurse, whoever is dealing with the patient, I think that’s the key.  

So, a bi-directional exchange of ideas, what’s important to you as the patient? What’s important to the caregiver? What are the worries? What are the barriers? Designing a treatment system around that, a treatment paradigm and approach. Discussing risks, benefits, side effects, toxicities, alternatives, and then a constant dynamic reevaluation throughout. That’s what I pictured. It has to be a journey and a partnership.  

Katherine Banwell:

Well, part of making care decisions is setting goals, and I think you’ve just alluded to that. What are treatment goals for myelofibrosis, and how are they determined?  

Dr. Naveen Pemmaraju:

That’s a great question. Myelofibrosis treatment goals are changing in real-time. I would say as of this recording, 2024, the main three things that I want patients to think about and the caregivers.  

Number one is a stem-cell transplant eligible or not? It used to be based on age and comorbidities, but there are other factors. So, are we going to stem cell transplants or not? That determines a lot of the journey. Two is a clinical trial or not. So, are we doing the standard of care therapy, often one pill at a time, or clinical trial, either an IV drug, a pill, or combinations? Then three is that dynamic assessment that we talked about, which is what are the goals of care? Often our patients with myelofibrosis have decreased quality of life, enlarged organs, fatigue, cachexia, and malnutrition.  

These are the central components. A lot of times they’re due to the myelofibrosis itself. So, the treatments may improve that. A lot of times it’s the other comorbidities, other health issues. So, working with the PCP, the primary care provider, and the local team. In my case, many of my patients are referrals, as you know, the local MD team. I think these are the three components, transplant eligibility or not, clinical trial versus standard of care. 

Then once we’ve made a treatment decision, minding toxicities and quality of life.  

Elevate | What You Should Know About Your Role in Myelofibrosis Treatment and Care Decisions

How can you elevate your overall myelofibrosis care and treatment? Dr. Naveen Pemmaraju discusses the importance of engaging in myelofibrosis care decisions with your healthcare team, shares advice for setting treatment goals, and reviews factors that may impact therapy options. Dr. Pemmaraju also provides tips and resources for self-advocacy, including coping with emotional health.

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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Transcript:

Katherine Banwell:

Hello and welcome. I’m your host, Katherine Banwell. Today’s webinar is part of the Patient Empowerment Network’s Elevate Series to help myelofibrosis patients and care partners feel well-informed when making treatment decisions with their healthcare team. On today’s program, an expert will join us to share advice for accessing better overall care. 

Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining us is Dr. Naveen Pemmaraju. Dr. Pemmaraju, it’s good to see you again. Welcome. Would you please introduce yourself?  

Dr. Naveen Pemmaraju:

Oh, thanks, Katherine, and to Jamie and the team. I’m Dr. Naveen Pemmaraju, a Professor of Leukemia at MD Anderson Cancer Center in Houston, Texas. I also serve as the director for our rare disease program focusing on BPDCN and, of course, MPNs. Also, I want to mention, I have another hat, which is executive director for MD Anderson Cancer Network for Cancer Medicine. Thanks, Katherine.   

Katherine Banwell:

Well, thank you so much for taking the time out of your day to join us. I’d like to start by discussing your role as a researcher. You’re on the front lines for advancements in the myelofibrosis field. What led you here, and why is it important to you?  

Dr. Naveen Pemmaraju:

Well, I think it’s an important question to start with and one that we need to evaluate and dynamically reevaluate over time. I think really for me, two major themes, Katherine, that brought me to this point. One is the absolute desire to be there for patients who don’t have a voice. So, that means giving voice to the voiceless. It’s something I’ve always been good at ever since I was a youth, which is advocating for those who may not be able to or cannot advocate for themselves.  

So, this is the rare disease thread. A lot of my colleagues were going into lung cancer, breast cancer, and colon cancer, very important. We need folks there. However, those were common diseases, largely elucidated. I was always drawn to the more difficult-to-treat diseases, esoteric, and rare, and I think that’s one component, which is the patient voice.  

The second aspect is scientific interest. Again, in the more common tumor types and diseases, there’s a lot already known. So, many of the researchers and research being done is either derivative from that knowledge, Katherine, a or kind of secondary. I wanted to put my efforts and my team’s efforts and frankly, my life effort into trying to figure out new science, new pathways, new breakthroughs, new ideas, and new concepts. I find that in the rare disease space, that’s where I can do that. So, both from the humanistic patient aspect and the science aspect.  

Katherine Banwell:

Well, it sounds like it’s a challenge to you as well.  

Dr. Naveen Pemmaraju:

I think that’s a great point. So, while it’s intellectually satisfying and very important to pursue this, and I love my patients, the clinic, and my team, you make a really good point. Every day when I wake up, it is the challenge that really drives you, which is to try to improve not only the lives of our patients but the quality of life.  

Try to improve the education barriers, which are many, and then the access barriers, not only here in the U.S., but all over the world. Social media has helped that, democratization of information, and platforms like yours right now to get the message out there to folks who need it the most. However, you make a good point. We have a lot of challenges and a lot of barriers, and that motivates me to get up in the morning every day. 

Katherine Banwell:

When it comes to choosing therapy, Dr. Pemmaraju, it’s important to work with your healthcare team to identify what is going to work best for you. So, as a clinician, how do you define shared decision-making?  

Dr. Naveen Pemmaraju:

Very important. So, shared decision-making to me means a partnership. It means a journey that the patient and the providing team are about to embark on. It’s a very different approach than a one-way, I tell you, you do this. Instead, I see it as a bi-directional exchange of ideas.  

Each visit, each EPIC in-basket or EMR communication, each touch with the healthcare system, the pharmacist, the PA, nurse, whoever is dealing with the patient, I think that’s the key.  

So, a bi-directional exchange of ideas, what’s important to you as the patient? What’s important to the caregiver? What are the worries? What are the barriers? Designing a treatment system around that, a treatment paradigm and approach. Discussing risks, benefits, side effects, toxicities, alternatives, and then a constant dynamic reevaluation throughout. That’s what I pictured. It has to be a journey and a partnership.  

Katherine Banwell:

Well, part of making care decisions is setting goals and I think you’ve just alluded to that. What are treatment goals for myelofibrosis, and how are they determined?  

Dr. Naveen Pemmaraju:

That’s a great question. Myelofibrosis treatment goals are changing in real-time. I would say as of this recording, 2024, the main three things that I want patients to think about and the caregivers.  

Number one is a stem-cell transplant eligible or not? It used to be based on age and comorbidities, but there are other factors. So, are we going to stem cell transplants or not? That determines a lot of the journey. Two is a clinical trial or not. So, are we doing the standard of care therapy, often one pill at a time, or clinical trial, either an IV drug, a pill, or combinations? Then three is that dynamic assessment that we talked about, which is what are the goals of care? Often our patients with myelofibrosis have decreased quality of life, enlarged organs, fatigue, cachexia, and malnutrition.  

These are the central components. A lot of times they’re due to the myelofibrosis itself. So, the treatments may improve that. A lot of times it’s the other comorbidities, other health issues. So, working with the PCP, the primary care provider, and the local team. In my case, many of my patients are referrals, as you know, the local MD team. I think these are the three components, transplant eligibility or not, clinical trial versus standard of care. 

Then once we’ve made a treatment decision, minding toxicities and quality of life.  

Katherine Banwell:

Right, okay. So, you’ve touched upon the factors that are considered when choosing therapy for myelofibrosis. Let’s talk about test results. What sort of tests should be done following a myelofibrosis diagnosis?   

Dr. Naveen Pemmaraju:

Well, I think this is something that’s an active area of evolution. I think the good news is I can give you a few standard items. I think most, if not all, of our patients, will require a bone marrow biopsy to be done at baseline and possibly even later on to assess the status of the therapy. Now, in some cases, that may not be available or accessible due to patient preference or comorbidities.  

However, a bone marrow biopsy is a way to look inside and see how the bone marrow tissues are doing. Outside of that, for the blood tests, the two most critical sets are what we call a CBC and a CMP. So, CBC complete blood count. This is where you get your hemoglobin, platelets, and white blood cell count, very important to know at baseline and dynamically.  

Then the complete metabolic profile is very important, Katherine because we need to know how the potassium, kidney function, and liver function are doing. Then finally, I would also say you’ll see your provider add in other blood tests over time, depending on the particular case. Thyroid testing if it’s needed in the case of fatigue, just to name one example. So, I think these are the main categories.  

I think what’s also interesting over time is that this is an issue with us as well in the MPN clinic. You end up seeing your MPN provider and team so much that it’s easy to forget and lose sight of the primary care items too. So, this is a good time to remind folks to stay in touch with their MPN team, the provider, and their caregiver, whether it’s colonoscopies, mammogram, or prostate. I remember over the COVID pandemic time, especially, a lot of that was either sacrificed, forgotten, or on purpose put aside. So, let’s remind people in 2024 to remember to have that partnership as well.  

Katherine Banwell:

How does molecular testing affect treatment options and prognosis? 

Dr. Naveen Pemmaraju:

Right, yeah, I haven’t mentioned that yet because that’s something that we’re trying to layer into. I do find that to be the standard of care now in the treatment of myelofibrosis. What you’re asking about is very important. So, outside of the normal labs in bone marrow morphology, seeing what it looks like under the microscope, we’re starting to add three or four items. One is called cytogenetics, that’s chromosomes. You’re born with 46, so 23 from mother, 23 from father, for example, 46 total.   

Even though most people are not born with an MPN per se, those chromosomes can change and become abnormal over time. So, we want to know that, and that can help us tell low versus high versus intermediate risk. Two is the molecular test you ask about. Most people have heard of JAK2, that’s the most common out of myelofibrosis, maybe 50 percent to 60 percent of cases, JAK2V617F. However, did you know there’s also CALR, which is the second most common molecular mutation, and then MPL. 

Those three are the big three driver mutations. They make up roughly about 90 percent of our cases, 10% being so-called triple-negative. So, you’re negative for all three. When you do deeper sequencing, which is available now clinically, and we check that here, you will find almost always, some other mutation, ASXL1, EZH2, SRSF2, etc. It becomes an alphabet soup very quickly. However, I think basically you should know that there’s JAK2, CALR-MPL, the big three driver mutations, and additional molecular mutations.  

So, therefore we and others believe you should check these as standard. Finally, there’s also flow cytometry. Just want to give a shout-out to that. Most people haven’t heard of that. When you send your bone marrow for testing, in addition to the pathologist looking under the microscope with the human eyes, there’s also a test that does side scatter of light called flow cytometry. That helps to look at a deeper level, maybe the thousandth, maybe even down to the millionth level, what these cancer cells do.  

Katherine Banwell:

What sorts of questions should patients be asking about test results?  

Dr. Naveen Pemmaraju:

I think the number one and number two questions that I advocate for patients or on programs like this, I think the one question that may help a lot is this question of when you hear all the data and ask the question, “Hey, is there any other questions I should be asking that I’m missing?” It’s an interesting question, right? It’s almost a meta, right, kind of a situation. However, when you ask that, every time I’ve been asked in the clinic, it makes me pause and say, “Now that you mentioned it, X, Y, and Z.”  

So, I think it’s a good one to ask either your physician or whoever healthcare provider is in the room, again, nurse, or PA. It’s an interesting one, right? It kind of makes someone maybe even put themselves in your shoes. So, I like it as a device to make people pause in a busy clinic. Yeah, the second question that I think is a good one is to say, “While things are going well right now, I wanted to ask you, doc, what are some things that could happen in the next six months, one year, or two years, adverse events or abnormal things, and is there something I can do to plan for it?” 

Again, it may be somewhat of a theoretical question. The doctor may say, “Okay, right now things are going well,” but it kind of makes people think about contingency plans, and alternative things. Well, now that you mention it, there is this one side effect of this drug. I don’t know, I think those are two kinds of go-to questions that I want people to be equipped with.   

Katherine Banwell:

Yeah, that’s great advice. I’d like to add that if you, the viewer, are interested in learning more about myelofibrosis testing and treatment, PEN has a number of resources available to you. You can find these at powerfulpatients.org/MPN or by scanning the QR code on your screen.  

So, once all testing is complete and the patient has an accurate diagnosis, they’ll work with their doctor then on a treatment approach. You’ve touched on this a little bit, but  

What are the types of treatment available for people with myelofibrosis?  

Dr. Naveen Pemmaraju:

Yeah, thanks, Katherine. We’ll keep it general and standard of care. As you mentioned at the top, I’ll reiterate, that none of these are intended to be specific instructions for specific folks. However, in general, for the category of patients with myelofibrosis, in general, there’s not many treatments, unfortunately. As of 2024, we have only four standard JAK inhibitors. So, that’s this pathway we’re talking about, JAK-STAT. Interestingly, you don’t have to be JAK2V617F mutated. These are for the whole pathway.  

So, all patients with myelofibrosis, are intermediate to high risk. The first one, Katherine, is ruxolitinib (Jakafi), which has been around for more than a decade, and first in class JAK inhibitor. The second drug is fedratinib (Inrebic). The third is pacritinib (Vonjo), approved only in 2020 for those patients with less than platelets of 50. Then the myelofibrosis drug, momelotinib (Ojjaara), just approved not even a year ago, in September of 2023 for myelofibrosis with anemia. So, those four are considered as called JAK inhibitors.   

They are really the only targeted therapy class of drugs specifically approved in the MF space. Outside of that, there’s older and other drugs that me and others have used, if you will, so-called off-label or historical use, hydroxyurea  (Hydrea), interferon products such as pegylated interferon. Hypomethylators such as azacitidine (Vidaza) and decitabine (Dacogen), particularly in more advanced cases. Some of those drugs are borrowed from MDS and AML and have been around for decades.  

Then of course, finally, clinical trials. We really recommend folks, if they have the ability and feasibility, clinical trials, even in the first diagnosis setting. So, untreated, first therapy. These clinical trials, Katherine, are based on three factors. One is JAK inhibitor plus another agent. So, that’s kind of like a combination trial. Two is add-on agents. So, you’re already on the JAK inhibitor for a while, maybe it’s starting to not work. Then you add in a third agent.  

Then three is a completely novel agent beyond the JAK-STAT pathway. Then maybe we can even add a fourth one now as this is evolving in real-time, which is anemia-targeting drugs. Many of our patients have either transfusion-dependent or bad anemia. Some of the drugs that are being developed are specifically aimed at them.  

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.  

Katherine Banwell:

That’s exciting news. 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.  

Katherine Banwell:

Right. I’d like to get to a few audience questions that we received prior to the program.  

Dr. Naveen Pemmaraju:

Sure. 

Katherine Banwell:

Cliff wrote in with this question. “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.  

Katherine Banwell:

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.  

Katherine Banwell:

Okay. All right, this next question comes from Joel. “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 goimg to go for a transplant? Are you going to go to a clinical trial? Are you changing therapy? It would be nice to know.  

Katherine Banwell:

Right. All right, here’s one more from Diana. “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.  

Katherine Banwell:

Yeah, absolutely. Well, those were all great questions from our viewers. We ask that you continue to send them to question@powerfulpatients.org, and we will work to get them answered on future programs. I’d like to turn back to self-advocacy for a moment, Dr. Pemmaraju. 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.  

Katherine Banwell:

Financial concerns may weigh heavy on patients and families. While everyone’s situation is different, do you have advice for where patients can turn for financial support?  

Dr. Naveen Pemmaraju:

I think this is going to be the next great revolution. Just like I mentioned, the psychiatry, mood, and quality of life realm, I think this will be the next one of the next decade. I think largely it has been not even overlooked, just misunderstood. I’m an academic. I’ve been an academic my whole life, so I’ve never practiced in a private practice. So, some of these issues are quite difficult and foreign for many of us academic doctors.  

In the community setting, there’s a whole set of pressures. Then of course, as you mentioned, there is a whole theme of the pharmaceutical companies helping. In the case of the JAK inhibitors, many of them have patient assistance programs, which have been vital to our patients. So, I think that financial toxicity, that’s what you’re asking about, right, is going to be the next era, the next realm, has been severely underlooked at, really misunderstood.  

You know, I think at the academic centers, you know, obviously we have access to financial counselors, business office, those folks are invaluable. I see them as an essential part of our team, particularly on patients who are trying to get on clinical trials, etc. I think in the community aspect where many of our patients are treated, I think there’s going to be a challenge. So, we have to work with insurance companies, pharmaceuticals, local clinics.  

For patients who don’t have healthcare insurance, try to get them insurance, county systems, cache safety net systems. However, I think you hit on it. I think this will be a new vital sign. It’ll be a new toxicity. It’ll be a new aspect when we consider new drug approvals, and financial toxicity. 

Katherine Banwell:

As we close the program, Dr. Pemmaraju, what would you like to leave the audience with? Why are you hopeful about the future of myelofibrosis care and treatment?  

Dr. Naveen Pemmaraju:

You know, I am hopeful. I am very hopeful. I think the two biggest things that I’m excited about for our patients and their caregivers are one, the burgeoning clinical trial portfolio that we have all over the world.  

Very excited to see the interconnections from Asia, Europe, North and South America. We’re trying to make inroads into Africa and Australia as well. So, a true worldwide  effort for MPNs, particularly myelofibrosis and clinical trials. So, stay tuned for that. I think that’s an exciting aspect.  So, not just the existence of them, but the interconnectivity,  communication, improvement, and availability. I think the second aspect that I’m super excited about is the democratization of information.  

Honestly, 10 years ago, it was kind of difficult to find out information about these diseases, not 100 years ago, just 10 years ago. I really attribute social media and the interconnectivity of folks on these platforms to getting information out there. I would put this type of a platform as well in that same conversation, which is newsflash, nobody’s reading books anymore. Okay, there I said it. 

However, people do have time for a quick two or three-minute blurb while they’re in the coffee line. So, if they can watch a snippet of an interview like this. They can get an email blast about a community town hall. They can get a paragraph on the new drug that just came out. People can take in information in small amounts so I think we have to meet folks, Katherine, where they are.  

We cannot expect people to go to the library and open up a dusty book. I mean, that was in my generation 30 years ago. So, people are on their phones, let’s meet them on their phones. They’re online let’s meet them there. If you’re going to have an in-person town hall, make it high-yield, make it worth somebody’s time and energy and effort frankly, to leave their house to come. Finally, let’s make things affordable from an educational standpoint, if not free, to get the information to the people who need it the most. I’m hopeful about that. I think social media and online platforms have helped us with that.  

Katherine Banwell:

Yeah. Well, that’s great advice, Dr. Pemmaraju. I want to thank you for joining us today. It’s been a pleasure speaking with you.  

Dr. Naveen Pemmaraju:

Thank you so much, Katherine, to the team. I love doing these with you, and thanks for doing this good work.   

Katherine Banwell:

Thank you to all of our collaborators. To learn more about myelofibrosis and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us today.  

Overcoming Barriers in Myelofibrosis Care: Challenges Faced by Patients and Providers

Overcoming Barriers in Myelofibrosis Care: Challenges Faced by Patients and Providers from Patient Empowerment Network on Vimeo.

What are key myelofibrosis barriers and solutions for healthcare providers? Experts Dr. Raajit Rampal from Memorial Sloan Kettering Cancer Center and Dr. Jeanne Palmer from Mayo Clinic discuss common obstacles to myelofibrosis care and methods they’ve used to overcome barriers including collaborative care tips.

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Transcript:

Dr. Nicole Rochester:

Dr. Palmer, can you speak to some of the obstacles or barriers faced by healthcare providers themselves when treating myelofibrosis patients?

Dr. Jeanne M. Palmer:

I think one of the challenging pieces, you know, I know in Arizona, we have a pretty big catchment area, because there’s not only the Phoenix metropolitan area, but there are a lot of smaller communities scattered throughout Arizona. And I think one of the issues that we have is, let’s say I want to start somebody on a new medication that potentially has a side effect of anemia or something. Being able to manage them remotely is difficult, because a lot of times they may require a blood transfusion. Can they even get a blood transfusion where they’re at? Can they afford the 5-hour drive down to Phoenix to get that? So I think sometimes, even access to simple things, well, I guess it’s not that simple, but things like blood transfusions can be hard. Fortunately for labs, you’re often able to get them most places through various Labcorp, Quest, et cetera. But sometimes any type of infusional treatment can be really, really hard to get.

Dr. Nicole Rochester:

Thank you. Do you have anything to add, Dr. Rampal, with regard to barriers faced by providers?

Dr. Raajit K. Rampal:

No, I actually think that’s an important, that’s a really important thing. Because it depends on your area of the country and what access to resources patients have locally. If we’re thinking about this as sort of a hub and spoke model, that may be the outdated model. In other words, it’s not that people can afford to, you know, from a financial perspective or a time perspective, come into the major center and then go back. They need to get access to care locally, but you have to have the infrastructure, the healthcare infrastructure, if you will, to deliver that care. And that’s a difficult problem in many parts of the country.

Dr. Nicole Rochester:

Dr. Rampal, can you speak to unforeseen or maybe outdated practice-related barriers that may hinder your work and that of your colleagues with regard to myelofibrosis treatment?

Dr. Raajit K. Rampal:

Yeah, I guess my broad answer to this is that things are changing rapidly and the pace of change is accelerated. In other words, when we think about myelofibrosis, the treatment paradigm probably, if you think about the last 15 years, in the early part of that, things were kind of relatively static and now they’re not as new knowledge emerges, as new treatments emerge. And the challenge here, again, speaking in general terms is, as Dr. Palmer pointed out, this is a rare disease. It’s not something that’s frequently seen by physicians in the community. So how do you keep people up to date on something that is not the majority of what they do? It’s a very small percentage of what they see and do. And that’s an ongoing challenge. And I’m not sure there’s any perfect solution to that except for education. It’s just a question of how do you deliver that in a time-effective manner so that people can devote some time to getting up to date? But it is ultimately a good problem that things are changing rapidly.

Dr. Nicole Rochester:

Absolutely. And, Dr. Palmer, do you have any solutions or actions or things that healthcare providers can do as this treatment landscape rapidly evolves?

Dr. Jeanne M. Palmer:

I think it’s a real challenge because even when we look at sort of the dogma of like, well, what’s the response criteria? I mean, when you’re thinking of a lot of like solid tumors, you think, okay, did the tumor shrink a certain amount? Did the tumor go away? With myelofibrosis, when we think about even response criteria, it’s really challenging. So I think I agree education is part of it, and it’s trying to figure out how to distill down the really important components of how do you manage these patients day-to-day? We can talk about the COMFORT study and the MOMENTUM study and everything else all we want to, that tested, were major studies that tested the drugs that we use, but then the nuances of how to manage them day-to-day is something that I think we could probably improve upon how we educate.


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Considering a Myelofibrosis Clinical Trial? Questions You Should Ask

Considering a Myelofibrosis Clinical Trial? Questions You Should Ask from Patient Empowerment Network on Vimeo.

What questions should patients ask when considering a myelofibrosis clinical trial? Expert Dr. Gabriela Hobbs discusses how clinical trials may fit into a treatment plan and shares key questions to ask your healthcare team about participation.

Dr. Gabriela Hobbs is a hematology-oncology physician specializing in the care of patients with myeloproliferative neoplasms (MPN), chronic myeloid leukemia and leukemia. Dr. Hobbs serves as clinical director of the adult leukemia service at Massachusetts General Hospital. Learn more about Dr. Gaby Hobbs.

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Transcript:

Katherine:

So, where do clinical trials fit into a treatment plan? 

Dr. Hobbs:

So, it really depends on what is available at the site where you’re seeking care. Clinical trials come in a variety of different flavors. So, there may be a clinical trial for patients that are newly diagnosed, that are about to start a JAK inhibitor, for example.   

So, if you’re a patient that’s considering a JAK inhibitor to treat your spleen symptoms or your systemic symptoms, and there happens to be a clinical trial for adding on another medication, like the first JAK inhibitor you receive, well, that’s a great place to consider a clinical trial.  

There may also be clinical trials in later lines. Let’s say you were treated only with a JAK inhibitor first, but the study that’s available at your center is adding another medication to the JAK inhibitor if the JAK inhibitor by itself didn’t quite do the trick. 

There’s also other studies, for example, at the time of transplantation, for example, using the JAK inhibitors during transplant. So, really the clinical trials can be relevant at any time during treatment. In addition to clinical trials, testing new medications, there’s also other ways to participate in research throughout your time as a patient with your care team, which may include things like, for example, consenting to participate in a tissue bank.  

You donate a sample of your blood or bone marrow that is then later on used for research. Or we may have studies investigating the symptoms a patient has throughout their disease or their experience living with their disease. So, there’s many different ways of participating in research and clinical trials, even if those don’t necessarily include trying a new medication.   

Katherine:

What questions should patients be asking if they’re interested in learning more about clinical trials? 

Dr. Hobbs:

Yeah, great question. So, the first is understanding, you know, what is the medication that you will be receiving? Are you going to be receiving a placebo? Is that an option? This means a sugar pill. That’s a common question that I get. How do you get assigned to different groups? So, in one trial, there may be a group that gets one dose, another group that gets another dose, et cetera. So, it’d be important to know how are you going to get assigned and what are the options potentially for you before you sign up.

After that, it’s important to know what phase the study is in. So, is this a first-in-human study where your doctor may not be able to tell you a whole lot about what’s expected in terms of side effects or safety or toxicity? Or is this a Phase III study where maybe the trial has been open for many years and there’s been many patients that have been enrolled in it already? Or maybe this is a drug that’s already been approved for another condition and we’re borrowing it for myelofibrosis, for example, and then your care team can tell you lots of information about the safety and toxicities, etc.  

So, having a sense of where the drug is in its development, I think can be very helpful. Then there are some practical things that we sometimes do not spend enough time talking about.  

So, I’m glad to have the space to talk about that here. Participating in a clinical trial takes time. And it’ll take more time as a patient to participate in a clinical trial than to receive regular care. You may have to go to the hospital where you’re being treated more frequently. If you’re somebody that receives virtual care where some of your visits are telehealth and some of them are in person, you need to be aware that you may have more visits that are in person because the clinical trial procedure requires that certain labs or tests be done in the facility, not anywhere else. Clinical trials by definition, unfortunately, sometimes have to be very inflexible in order to ensure that we collect data in a uniform way.  

So, just being aware that it may take more time to participate is important. And along those lines, asking if the clinical trial will reimburse you for some of that time. So, for example, if you need to park in the expensive hospital parking more frequently, some trials will actually reimburse you for that. Or they may offer a hotel reimbursement if you need to travel from far away and spend a night there. So, don’t be afraid to ask those things because many times that’s built into the clinical trial.

So, that’s an important thing just practically to know. So, asking for a study calendar so you get a sense of how frequently you’ll need to be going to the doctor is really important. Also, then realizing that potentially you may have to go to see the doctor or the care team more frequently initially, but then after the first couple of months, if everything is going well, you’ll likely have the flexibility to go less often. So, all those questions are important to have in mind.  

What Are the Currently Approved Myelofibrosis Therapies?

What Are the Currently Approved Myelofibrosis Therapies? from Patient Empowerment Network on Vimeo.

Expert Dr. Gabriela Hobbs shares an overview of available therapies and important considerations when choosing a myelofibrosis treatment plan.

Dr. Gabriela Hobbs is a hematology-oncology physician specializing in the care of patients with myeloproliferative neoplasms (MPN), chronic myeloid leukemia and leukemia. Dr. Hobbs serves as clinical director of the adult leukemia service at Massachusetts General Hospital. Learn more about Dr. Gaby Hobbs.

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Transcript:

Katherine:

Would you provide an overview of the currently approved therapies for myelofibrosis?  

Dr. Hobbs:

Sure, absolutely. So, I’ve alluded to this a little bit. So, in 2011, we had the first JAK inhibitor approved called ruxolitinib, the brand name is Jakafi. After that, we had the approval of Inrebic or fedratinib and then pacritinib or Vonjo, and then most recently momelotinib or Ojjaara. So, we have four different JAK inhibitors that are now approved for myelofibrosis.   

So, who needs to get a JAK inhibitor and how do we choose between the JAK inhibitors? So, the traditional indications for JAK inhibitors are, does a patient have bothersome symptoms from having a big spleen? Does a person have symptoms from their disease? Symptoms can include things like night sweats, itching, unintentional weight loss, brain fog, and fatigue. Fatigue can be challenging because of course many things can cause fatigue. But those are some of the symptoms that can occur with having this disease. So, if a patient has both splenomegaly symptoms or one or the other, they’re eligible for a JAK inhibitor.  

So, just having myelofibrosis doesn’t mean that you need to have a JAK inhibitor right away. Probably the most commonly used JAK inhibitor, and this will be the case probably for a long time, is ruxolitinib.  

The reason for that is that it’s been around for a long time, and it’s a very well-tolerated medication. Patients that have platelets that are very low, meaning platelets that are less than 50, should be considered for pacritinib first, as that’s the indication for that agent. Patients that don’t do that well on ruxolitinib initially, let’s say that the dose gets increased and the spleen and the symptoms are still present, but still have good blood counts, are good candidates for then receiving fedratinib. Fedratinib can also be given upfront. It rarely is given upfront, simply because ruxolitinib has been around for longer and it’s a better-tolerated medication.

So, therefore most providers feel more comfortable giving that upfront. I have had some patients that are concerned about the weight gain that is a side effect of ruxolitinib. For those patients, I’ve occasionally considered giving fedratinib first before ruxolitinib. And then lastly, we have momelotinib. It’s approved primarily for patients with myelofibrosis and anemia.  

Now momelotinib is still a JAK inhibitor, so it can still improve symptoms, and it still improves spleen size. So, I struggle with that recommendation of just using it for anemia in patients that don’t have splenomegaly or symptoms.   

But the FDA label was pretty broad, and it’s important to recognize that. So, how is momelotinib being used? It can be used in the upfront setting for patients that have spleen and symptoms, and also anemia, meaning low red blood cell levels. Or,  it can be used for patients that have been treated with a JAK inhibitor first and then develop anemia. So, momelotinib is given to continue to improve the spleen and symptoms, but also help the anemia.

So, that’s kind of like an overview of the four JAK inhibitors. Now we have a group of patients that maybe doesn’t have a lot of spleen symptoms or symptoms in general but has issues with having low hemoglobin. So, for those patients, we’ve used a variety of different medications, including medications that are called erythropoietin, which is a hormone that helps to boost the red blood cell levels.  

 A medicine that’s similar to testosterone that can also help boost the red blood cell levels called danazol (Danocrine). And then there’s a medication called luspatercept-aamt (Reblozyl) that has been approved for a related condition called myelodysplastic syndrome. And in some clinics, it can be used even though it’s not approved either by itself or in combination with ruxolitinib.

And then lastly, patients that have what is called high-risk myelofibrosis, meaning they have some mutations that may indicate that a patient has a higher risk of having complications of their disease, or they have very low blood counts, are usually considered high-risk. Those patients should be recommended and referred to transplantation as soon as they’re identified as having high-risk disease.  

Katherine:

When you say transplantation, you’re referring to stem cell transplant. 

Dr. Hobbs:

Yes, and I’m glad you said it that way actually. So, stem cell transplantation or bone marrow transplantation, same thing, interchangeable, same procedure. You got it.  

Katherine:

When considering therapy, how do you approach a treatment plan for someone diagnosed with myelofibrosis?  

Dr. Hobbs:

Great question. So, when approaching how I care for a patient with myelofibrosis, I take several things into account. The first thing is, who is this patient? What other medical conditions do they have? How impacted are they by their myelofibrosis? Then what I like to do is to plug in the numbers of the patient, their blood work, their mutations, etcetera, into one of the many risk calculators that we have to determine what the risk of their myelofibrosis is.   

If a patient is considered high-risk, I will generally consider transplantation or discuss a referral to a bone marrow transplantation in one of our first visits, if not the first visit. After that, I need to determine whether or not the patient has symptoms from their disease, and if so, if they should receive a JAK inhibitor. Then I’ll look through their blood work, what their symptoms are to decide which JAK inhibitor to use first.   

If really the spleen and symptoms aren’t the primary issue, if it’s more related to low blood counts, then we can think about treatments directed at improving the hemoglobin, for example. There may be a group of patients that don’t actually require any treatment when I first meet them. So, just providing them with education, what to expect. Then discussing more of the psychological impact of living with a condition and approaches to handle that, maybe more the focus of my care.

And in general, for most of my patients, we also talk about the rest of the care. So, not just what the blood work is and what medicine I’m going to start them on, but also other things that they can do to take care of themselves, including making sure that they are actively monitored by their primary care doctor or by other specialists if that’s still appropriate. You know, one of the things we don’t discuss that frequently in myelofibrosis, we discuss that more often in essential thrombocythemia or polycythemia vera is a risk of blood clots.  

But the truth is that myelofibrosis patients can also have risks of blood clots. So, therefore, making sure that patients with MF that may have issues like hypertension, diabetes, high cholesterol, etc., get those well-managed is also really important to prevent them from having blood clots. So, lifestyle management is also an important part of the care of a patient with myelofibrosis.  

Myelofibrosis Clinical Trial Participation | How Does It Move Research Forward?

Myelofibrosis Clinical Trial Participation | How Does It Move Research Forward? from Patient Empowerment Network on Vimeo.

How do clinical trials move myelofibrosis research forward? Expert Dr. Gabriela Hobbs discusses the purpose of clinical trials, factors that may impact participation, and how trials can benefit patients.

Dr. Gabriela Hobbs is a hematology-oncology physician specializing in the care of patients with myeloproliferative neoplasms (MPN), chronic myeloid leukemia and leukemia. Dr. Hobbs serves as clinical director of the adult leukemia service at Massachusetts General Hospital. Learn more about Dr. Gaby Hobbs.

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Considering a Myelofibrosis Clinical Trial? Questions You Should Ask

Transcript:

Katherine:

Dr. Hobbs, a key part of research moving forward is the clinical trial process. Can you talk about the benefits of patient participation? 

Dr. Hobbs:

Yeah, so I think to answer that question, I should preface that by saying that I conduct clinical trials, and so certainly my answer is going to have that as a bias, so it’s important to know that. And I tell my patients that as well when I’m talking to them about clinical trials. Now, why do I think clinical trials are beneficial? Well, there’s really no way to advance the field without the sacrifice that patients do by allowing us to conduct clinical trials.

Without clinical trials, we cannot get drugs approved. Without new drugs, we certainly can’t help our patients anymore with newer therapies. That being said, a clinical trial is something that is not just an experiment. Many times patients will be like, well, I don’t want to be a guinea pig. And I completely respect that.  

So, I think it’s really important to recognize too, that we take conducting clinical trials very, very seriously. The machinery that needs to exist in each hospital to conduct trials includes a ton of people. So, we have a lot of regulatory bodies, both within the hospital and outside of the hospital, to ensure that clinical trials are conducted in an ethical and in a safe way. So, one of the benefits, which you may not consider when you’re contemplating participating in a trial, is that your care team actually becomes much larger. You’re much more closely scrutinized actually, when you’re a member of a trial.

So, whereas before you would have just primarily seen me and my nurse practitioner, when you participate in a clinical trial, all of a sudden you have all these research nurses that are calling you, checking in with you, making sure you’re feeling well, et cetera. So, that’s actually a nice perk to participating in trials. So, an important thing to know with clinical trials is that they may not benefit everybody.  

And that not every clinical trial may be right for you and that there may be times when trials are appropriate and times where trials may not be appropriate. So, it’s not a decision that you make that’s black and white and that’s a decision that you make forever. I think it’s something that you can continue to discuss with your care team as you go through having this disease. 

Which Emerging Myelofibrosis Therapies Are Showing Promise?

Which Emerging Myelofibrosis Therapies Are Showing Promise? from Patient Empowerment Network on Vimeo.

What are the latest advances in myelofibrosis therapy? Expert Dr. Gabriela Hobbs discusses various inhibitor therapies, including BET inhibitors, that are currently being studied in clinical trials for patients with myelofibrosis.

Dr. Gabriela Hobbs is a hematology-oncology physician specializing in the care of patients with myeloproliferative neoplasms (MPN), chronic myeloid leukemia and leukemia. Dr. Hobbs serves as clinical director of the adult leukemia service at Massachusetts General Hospital. Learn more about Dr. Gaby Hobbs.

Download Resource Guide

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Myelofibrosis Clinical Trial Participation | How Does It Move Research Forward?

Transcript:

Katherine:

Can you share with the audience how the field of myelofibrosis has changed over the course of your career? 

Dr. Hobbs:

Yeah, so it really has been a very exciting journey. So, when I was in medical school, I think that we basically had just discovered the JAK2 mutation.  

So, in the course of my own training and then my professional career, we’ve gone from myeloproliferative diseases being conditions where we really didn’t necessarily have a reason why people would get these conditions. Now not only do we know about the JAK2 mutation, but we know about many other mutations that patients can have. Then in 2011, the first JAK inhibitor was approved, ruxolitinib (Jakafi), and since then, three additional JAK inhibitors have now been approved, including pacritinib (Vonjo), fedratinib (Inrebic), and most recently, momelotinib (Ojjaara).  

So, the field has definitely advanced concretely in that regard. But we also just have much more information about how to diagnose these conditions and also how to treat them. Outside of the JAK inhibitors, we’re better at recognizing when patients need to go to get a bone marrow transplant. For example, and our outcomes with bone marrow transplantation have improved significantly. We also have many other treatment approaches that wouldn’t have existed before, and we also recognize that patients with MPNs live with a lot of symptoms. So, I think that we’re better at just the doctoring part of taking care of patients with MPN. So, definitely, the field has just really, really changed significantly in the last two decades.  

Katherine:

What are new and emerging therapies that are showing promise?  

Dr. Hobbs:

Yeah, so the list is long and it’s getting longer. So, in addition to the fact that we now have four JAK inhibitors approved, which is worth just remembering that, because not that long ago we only had one, and one of them was just approved less than six months ago.   

There are many new agents that are being studied in combination with the JAK inhibitors. This past year at the American Society of Hematology meeting, which is the annual meeting where we go to share our research and learn from our colleagues, there were two Phase III studies that were presented at the same time.  

I can’t remember, or I don’t think, but that has really ever happened before for myelofibrosis. One of them was with an agent called pelabresib, which is a type of molecule called a BET Inhibitor. And the other one was with an agent called navitoclax, which is an agent called a BCLXL-BCL2 inhibitor, which is a molecule that helps cells to undergo apoptosis or programmed cell death.   

So, these molecules were both combined with ruxolitinib. And we saw the results of the Phase III studies for each of these agents, and they were really quite exciting. The punchline for both of these studies is that they demonstrated that when you give two drugs as opposed to just one, the amount of patients that have a significant reduction in their spleen is doubled than when you give ruxolitinib in it by itself. So, for some of our patients that is a really meaningful number. You know, if you’re a patient that suffers from a big spleen, knowing that there’s a possibility of having two drugs that you can take to really shrink that spleen in a significant way, I think is very, very promising. On the symptom front, taking two medicines versus one medicine really didn’t seem to make a huge difference. I think we can analyze this in two different ways.  

We can see the negative or the positive side of this. So, on the negative side, well, it’s too bad that, you know, added medication didn’t help patients feel better. But on the upside, it’s also good that taking two medicines didn’t make people feel worse. Sometimes you can think of, you know, if you’re taking more medication, maybe you will feel worse. So, the jury is kind of still add on the significance of those results.

But regardless, without getting into too much detail about these studies, I think it’s really exciting for myelofibrosis patients to know that there are two agents that are in Phase III testing. That means that the next step is really consideration of FDA approval. So, when medications go through clinical trials, they go through earlier phase studies, Phase I, Phase II, and then finally they get to Phase III. A lot of work and effort has gone into these two compounds to try to get them to FDA approval. So, we’ll wait and see if in the next year or so we have new agents for the treatment of MF. 

In addition to these two, which of course are the most advanced, there really are a variety of other agents that are being tested. Those, for the most part, are still in Phase II testing. And similarly to the ones I mentioned before, most of the compounds, the way that they go into trials is first they start out showing that they’re safe by themselves, and then they get added to a JAK inhibitor.

So, far, because ruxolitinib has been the one that we’ve had around for the longest, most of these studies are being tested in combination with ruxolitinib. But we start to hear rumblings from clinical trials that perhaps some of the newer trials will consider using other JAK inhibitors as combination partners, which is a natural evolution. So, to name a few other agents, we have drugs like selinexor (Xpovio), and navtemadlin we have a PIM kinase inhibitor, a lysyl oxidase inhibitor, an LSD1 inhibitor, the list is long of all these different agents.  

Preliminarily, at least from the data we’ve seen from all of these compounds, I think there’s a lot of room for excitement. We see that combining these drugs together, the new agent plus the ruxolitinib, leads to a significant reduction in the spleen. And in some of these agents, we’re starting to see other endpoints. So, in addition to just looking at can we make patients feel better and can we shrink their spleens?

We’re starting to look at other things such as when we add these medications, do we see a reduction in the scarring or the fibrosis in the bone marrow? Do we see a decrease in the cells that have the mutation? Do we see the patients live longer? All of those things are endpoints in our studies that we really haven’t tested before. So, I think the field really will produce a lot of exciting data in the next couple of years.  

Katherine:

You mentioned clinical trials, and we will talk about those in a few moments, but are there innovations in technology that are accelerating myelofibrosis research?  

Dr. Hobbs:

So, the most obvious way to answer that question is simply that it’s much easier to diagnose myelofibrosis now, thanks to the ability to do genetic testing now much more easily than before. So, I think that previously, you know, getting JAK2 testing or testing for the other mutations was not as simple or would take a long time for the results to come back.  

Now, you know, I see even in the smallest of practices, ordering not just the JAK2 gene, but ordering what many of us do, which is like a panel of genes, where you test for a lot of the genes at the same time, has become almost commonplace. So, that’s really a meaningful advance in that it’s a technology that’s available and it’s no longer as prohibitively expensive as it was before.  

That doesn’t mean that some patients don’t end up getting charged in ways that doesn’t make any sense anymore, but that’s a conversation for another time. But I think just having the ability to make those diagnoses because of how easy it is now to test for these mutations is really very meaningful. Outside of that, I mean, I would say that along with the improvement in the knowledge of what mutations patients have with myelofibrosis, we definitely have deeper ways of analyzing what genes are being expressed and in what cells they’re being expressed to really understand, you know, when do patients first get those mutations and how do those mutations change over time.

So, we’re really diving deep into the actual biology of the bone marrow and there’s some studies that have demonstrated that patients may even have the JAK-2 mutation in utero, which is really, really fascinating. So, definitely a lot more understanding of the actual biology of how these diseases happen.   

Primary vs Secondary Myelofibrosis | What’s the Difference?

Primary vs Secondary Myelofibrosis | What’s the Difference? from Patient Empowerment Network on Vimeo.

How are primary myelofibrosis and secondary myelofibrosis defined? Expert Dr. Gabriela Hobbs explains the differences between the conditions and discusses a common scenario that secondary myelofibrosis patients often experience. 

Dr. Gabriela Hobbs is a hematology-oncology physician specializing in the care of patients with myeloproliferative neoplasms (MPN), chronic myeloid leukemia and leukemia. Dr. Hobbs serves as clinical director of the adult leukemia service at Massachusetts General Hospital. Learn more about Dr. Gaby Hobbs.

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Transcript:

Katherine:

There may be some confusion, Dr. Hobbs, among people wondering what is the difference between primary and secondary myelofibrosis? Could you describe the differences?  

Dr. Hobbs:

Sure. Great question. So, that term, primary and secondary, is actually used in medicine very frequently for the description of many conditions that are not that different. So, primary means a patient has myelofibrosis and did not have any myeloproliferative neoplasm, or MPN, before their diagnosis.  

So, they went to the doctor and the first diagnosis they received was a diagnosis of myelofibrosis. Now sometimes we suspect that a patient may have had another MPN previously, such as essential thrombocythemia or polycythemia vera, but they just weren’t diagnosed.   

What I mean by that is, you know, let’s say you meet a patient and you look through their chart and you see that five years ago or 10 years ago, they had really, really high platelets or very high red blood cell numbers. So, there you could say, well, you know, you were never diagnosed with ET or PV, but maybe you had that.

So, you probably have secondary myelofibrosis, but the diagnosis, you know, that you come with to the doctor is myelofibrosis. So, secondary myelofibrosis means that you had an underlying condition before, meaning you were first diagnosed with one condition like PV, polycythemia vera, or ET, and then those conditions turned into myelofibrosis.  

And then we call that secondary myelofibrosis, meaning it is secondary to the primary condition, meaning ET or PV. One area of confusion that I’d like to be able to clarify also related to this is if a person has secondary myelofibrosis, they don’t have two myeloproliferative neoplasms or two conditions. It is one and the same. They just live on a spectrum and over time, they can turn into, one into the other. So, it’s not that you now have two diagnoses, it’s still the same condition, it’s just morphed a little.