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.
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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 cri