A Dynamic Disease That Does Not Stand Still: An Overview of Myelofibrosis

Lindsey Lyle

Tajuana, I’m excited to be here with you this afternoon to discuss the rare blood cancer myelofibrosis, and the exciting progress that has been made in available clinical trials and approved treatment options for our patients. I’d like to start this conversation with a brief disease overview, really getting back to the basics of myelofibrosis prior to diving into more nuanced details of disease management. Hopefully, this review will be valuable to both those APs who have been in practice for quite some time but may see very few patients with myelofibrosis, and also for new APs who are just getting started in heme-onc. We want to provide them with a little bit of background information on how to understand this disease and therefore provide excellent care for patients.

At a very basic level, it is important to remember that myelofibrosis is a blood cancer. The terminology surrounding myeloproliferative neoplasms, the umbrella under which myelofibrosis fits, has evolved from previously being described as a myeloproliferative disorder. I think this nomenclature has influenced in some respects where patients with MPNs are seen within an institution, with many in the benign hematology clinics. What are your thoughts on this? And just at the very basic level, how can we effectively communicate this to underscore the gravity of this disease process, albeit heterogenous?

Tajuana Bradley

Lindsey, I am thrilled to be here with you as well. You make a really good point in regard to many patients being managed in benign hematology clinics. Oftentimes I find that our patients and clinicians don't realize that this is actually a blood cancer and not a benign condition. My patients are shocked when they are told they have a blood malignancy. I think as a community we need to acknowledge that this is a blood cancer and get back to the basics of understanding what's going on, while reinforcing to our fellow APP colleagues that these patients have a bone marrow that's not working correctly. I often start by explaining that myelofibrosis is a rare, chronic blood cancer that can also "progress," or get worse over time. For example, new symptoms may appear, or existing symptoms may get worse. With MF there may be an abundance of cells or too few blood cells that leads to some of the presenting symptoms; however many patients may not experience any at initial diagnosis. While blood counts are an important aspect in the diagnosis and management of MF, it’s not just about the blood counts. Oftentimes, we see these numbers and get focused on what the numbers look like, but with these patients, they often look well while having a significant symptom burden.

It's also important to understand the bone marrow in MF has this overproduction of cytokines that causes inflammation within the bone marrow. This increase in cytokines leads to an overproduction of cells in the bone marrow. People with MF have a defect in their bone marrow that results in an abnormal production of blood cells, causing scar tissue to form. MF can result from a progression of other bone marrow diseases, like essential thrombocythemia or polycythemia vera or it can occur on its own. This is known as primary myelofibrosis.

Patients begin to experience symptoms like fatigue, weight loss, itching, and night sweats. Over time they may develop splenomegaly. That to me is one of the biggest burdens that we see in our patients. Splenomegaly leads to pain and early satiety. Leukocytosis, anemia, and thrombocytopenia may also be seen in MF patients. Understanding the pathophysiology of the disease and educating folks around us to keep them current will enable us to engage with our patients and their caregivers. It is also important to know symptom burden doesn't always correlate with the blood counts. Patients may come in one visit and their counts may indicate things are going well, but when you get to talking to them about how they feel, that's when you really understand the burden of what's going on with them. So, in practice, we need to stay engaged and really understand that MF symptoms can have an impact on our patients’ quality of life. Splenomegaly is an important clinical indicator in patients with MF, and I find that spleen assessment can be a powerful tool to help monitor disease progression.

Lindsey Lyle

I completely agree with you. It's so key to keep in mind that while we have objective evidence of some level of disease characterization in the bloodwork, that's not the full picture.

Tajuana Bradley

Right. As the bone marrow’s inability to make enough normal blood cells progresses, the spleen begins to take over or become this extramedullary organ to manufacture them, which causes the spleen to grow.

Lindsey Lyle

When approaching a patient, whether newly diagnosed or not, it’s important to remember that there are a number of clinical features that go into disease risk categorization. And this includes not only blood counts, but also symptoms. The presence of constitutional symptoms is a negative prognostic feature. And if we're talking about trying to estimate overall survival for these folks, a patient with low-risk disease may have a median overall survival of about 15 years, but patients with high-risk disease only have 1.5  years. That's a significant difference, and unfortunately a pretty poor median overall survival for our high-risk patients. So, it's really important for advanced practitioners to understand what features of disease contribute to being high risk so that they can properly have conversations with the patient as it relates to setting goals for treatment and being realistic about challenges ahead.

One of the best things I was ever taught by a mentor of mine, which seems so basic, is when approaching these patients, explain to them that we want to change the outcome. So, if you’re having a conversation with a high-risk patient, you're not saying, "Your median overall survival is one and a half years.” Rather, “How can we work together to change this and help you live your desired quality of life for as long as possible?" And there are a lot of things that we'll talk about later on about how we can perhaps change that. But the point of bringing it up this way is just to home in on the fact that yes, this can be a very aggressive disease, and it requires really astute recognition and management, to your point, of both symptom burden and also blood count abnormalities. When you're talking about symptoms, you're talking about in part the result of overactive cytokines and splenomegaly. By and large, fatigue is the number one complaint that our patients experience. Is that the same for you, Tajuana?

Tajuana Bradley

Yes, it really is. In my experience, I’d say the majority of my MF patients experience some level of fatigue. Fatigue can be such a vague report by our patients. It really is challenging for us to figure out how to help them manage and mitigate their symptoms. I’ve gotten in the habit of asking more direct questions when assessing fatigue, like, “Are there things you once enjoyed doing 3 months ago that you can’t do any longer?” Patients are then able to give more insight into how their experienced fatigue is impacting their day-to-day lives and overall quality of life.

Hearing you talk about having conversations about a patient’s risk classification, if someone is high-risk vs low-risk, I’d like to know how you approach those conversations with patients when you're with them and trying to get them to understand not only the disease process but also their prognosis? What tools are you using to help you navigate those conversations with patients?

Lindsey Lyle

I try to be well-prepared before entering a room with the patient. That’s critically important. Reviewing historical blood counts, disease features, and pathology reports—maybe this is the first time we're seeing them after a bone marrow biopsy. Perhaps we’re delivering the diagnosis in addition to any prognostication that we might be able to do. I believe having a well-informed patient is important because if I were in their shoes, I would want transparency with my providers. I'm very open with my patients about what the tests show and what that means as far as treatment plans and goals of care. I also try to break disease features down into smaller categories, as this helps patients feel a bit more organized as far as the main clinical problems that need to be addressed. I explain that we know much more about myelofibrosis now than we ever have, and that we’re learning about how certain molecular mutations may impact how the disease may behave.

I do tell my patients, "This is a blood cancer. It more often behaves like a chronic blood cancer. There are things that can change at any point in time that can make your disease more aggressive or more accelerated. The only way we're really going to know how your disease is behaving is by watching you and tracking you over time," which most times is not what patients want to hear. They want to hear, "You’re going to live for 20 more years and you’re going to be totally fine." It's hard to deliver this news, but I always try to frame it with hope because I don't think that it should be without that. We have come quite far in the way that we treat this disease and the treatment options available to patients.

I also let them know, "We’re in this together, I'm on your team. Let's try to fix what we can and help you feel better while doing what we can to maximize your quality of life for as long as possible." And a lot of times, I really try to focus on what the key clinical problems are because we can get so lost in, "Oh my gosh, there is so much going on, abnormal cytokine production, blood count abnormalities and splenomegaly," but maybe not for everybody, right?

Tajuana Bradley

Right, for some it may be bone pain and night sweats. I agree with you that delivering the news for the diagnosis of MF is difficult, but like you stated, framing it with hope eases the shock and disappointment. Transparency is key, and I welcome it when engaging with my patients.

Lindsey Lyle

After we go over the disease process and risks of the features of their disease that make them higher or lower risk, I say, "But let's look at you. What are you experiencing? What are you feeling from a symptom perspective? Let's try to address that. What are your blood counts telling us? Is your blood work looking okay, or do we have something that we really should try to improve?" And going in that direction really helps keep everybody grounded because we have some things to focus on.

Tajuana Bradley

Exactly. When you say track symptoms, it makes me think about the fatigue, as we mentioned earlier. All of our patients are tired, so how do you quantify that? How can you really home in on the fatigue? I've learned to ask what the patients do for a hobby, what they do for work, and how the fatigue is impacting their life. And I'm doing this when I'm training new hires. How is the fatigue challenging the patient? Can they still go out with their friends and meet up for that Friday night movie? Are they able to work without taking a lot of breaks? I’m trying to get them to tell us how the fatigue is really impacting them instead of them just saying, "Oh yeah, I'm really tired." That's something that I think about in terms of tracking symptoms.

And particularly with the spleen, patients and other clinicians may not always know that someone has a huge spleen. So I've gotten in the habit of asking patients if they’re having any pain on their left side. Are they able to lie on their left side? Because we know that that can be a telltale sign that something's going on. As clinicians, we have to know the symptoms and talk to the patients, find out what's really going on with them. It'll help us to assess whether there's potentially any change or anything going on in terms of their myelofibrosis.

Lindsey Lyle

Absolutely. You're exactly right. It's a dynamic disease that does not stay the same.

Tajuana Bradley

Right. As we know, their disease can change over time, and so can their symptoms.

Lindsey Lyle

We need to know how things are changing. I know you’re responsible for onboarding new APs, so for these new APs who are really trying to understand myelofibrosis, I was just thinking of a couple of resources that were particularly helpful to me when I started. I find the “How I Treat” articles that are published in Blood to be so helpful. I mean, they're high level, but they're also very well-done articles that help describe the disease process, prognostication, and current treatment landscape. Additionally, the JADPRO MPN Resource Center¹ is also very helpful. There's a Fast Facts tab on the webpage. It’s a great place for APs who are not as familiar with MPNs to go, especially for background information on the different MPN subtypes. And of course, there are the NCCN Guidelines.² I don't know if you have any places that you send people or resources that were your go-to for information as a new grad?

Tajuana Bradley

In addition to what you just recommended, I also have them check out Voices of MPN³ as well as MPN Connect.⁴ I distribute a printed symptom tracker from Voices of MPN that has pictures and annotations on it.⁵ The symptom tracker enables patients to track their symptoms from one visit to the next. I'll use that as I'm onboarding new APPs. They may not even be new grads but perhaps new to oncology in general. Of course, the NCCN Guidelines have detailed explanations of each disease process with an excellent discussion and literature review, so that's a good place to start as well.

Lindsey Lyle

Oh, I totally agree. And I like that you direct them to the patient tracking websites because that's so important. If they can understand what the patient is experiencing or thinking about, it helps the AP to make that connection with their patient and think, "Oh gosh. Okay, these are the things they're going to be watching for." And so, from my perspective as their provider, I want to really focus in clinically. That's a really good tip.

Tajuana Bradley

This is really good information for all APs to have. Thanks for chatting today, Lindsey.

Lindsey Lyle

Thanks to you too. This is such an important topic. Let’s talk again soon!