Symptom Management in Patients with Myelofibrosis and the Role of the APP

Sarah Profitt

I'm back with my colleague, Kate Kennedy. Kate is a nurse practitioner in the malignant hematology clinic at Vanderbilt University Medical Center. Kate, in our last conversation we gave some insight into my role as the oncology pharmacist in our clinic. This time I was thinking we could highlight the role that you, the APP, has in caring for our patients with myelofibrosis. Would you mind giving an overview of your role in clinic as a nurse practitioner?

Kathryn E. Kennedy

Yeah. So, the way our clinic is structured, our APPs have a little bit more clinic time. Because of the additional clinic time, we spend just a little bit more time with the patient, and that results in them really relying on us as the APP to help guide them through the process and sometimes interpret what the physicians have told them.

Where I see myself as the most helpful is in educating patients about the pathophysiology of the disease, what causes the symptoms of the disease, and medications and side effects of medications. I think a lot of times patients have symptoms that they don't even realize are related, like itching – they may have had it for years and have no idea that it's related to myelofibrosis. With the medication, expectation management with regards to time to response is incredibly important. So, for instance, when we think about myelofibrosis trials investigating momelotinib, response wasn’t evaluated until the 26-week mark. But we can continue to see patients gain transfusion independence even at the 1 year mark. I think that's an important thing to remind patients: even though we might see some response at 26 weeks, if we continue this drug, we might see even more of a response at 30 weeks and 45 weeks and 52 weeks.

I typically meet with a patient right after they're first diagnosed, either right before or right after they start a new medication. Usually this means we have a long-standing relationship; I know these patients really well, I know their grandkids, I know their spouse, and I know what they do for a living. I like to learn about them, about what's important to them and what their overall goal is for treatment. Are they really into playing golf? I’d want to know that so that we can hopefully get them back on the golf course. Maybe it's not for 18 holes, but maybe we can work up to 9. Are they still trying to work? Do they have kids? Do they have a pet they're trying to walk? All of those things are important to their quality of life. Especially since it's a disease of generally older adults, and transplant is not always an option, a lot of myelofibrosis treatment is focusing on quality of life.

At the first visit, we'll usually look at the Myeloproliferative Neoplasm Symptom Assessment and see where they're starting. The other thing that's important to remember is that although we might see several of these patients a week, this is their only experience with this disease, and they have no idea what other patients are experiencing. They don't know what's normal. Most of these patients have never heard of myelofibrosis before being diagnosed. I try to break down what myelofibrosis is and why they feel the way they feel, and explain what their new normal might look like. Also, explaining to them when to contact me is a big part of the first couple of visits. I think patients often get overwhelmed in those first couple of visits. Our second or third meeting might go something like, “When I saw you last, we talked about this. What do you remember from that conversation, or what questions do you have from that conversation? I know it was a lot of information.” I also try to assess how they communicate best; some of my patients need things written down for them in detail. Some of them do really well with videos. Some of them do well with just hearing it, and they want to write it down. But knowing that upfront is helpful.

Sarah Profitt

That is such great insight. I know I watch our patients develop deep and meaningful relationships with their APPs because of the continuity of care, and because of how frequently you all are seeing them, and how much you care about them as a person and get to know, like you said, what's important to them, what's going to maintain their quality of life, what they are looking forward to, and how we can help them continue those things.

One thing that you mentioned was the MPN Symptom Assessment and calculating what we call a Total Symptom Score (TSS). The TSS is a common clinical endpoint that's been used in landmark trials of the oral targeted agents used in myelofibrosis, and it's such a nice thing to see when patient-reported outcomes are used to assess new treatments because they take into account the patient experience. So, when you think about symptoms that patients with myelofibrosis experience and the impact that the disease has on their quality of life, which ones are you most commonly discussing with your patients?

Kathryn E. Kennedy

Ultimately it varies. Myelofibrosis is such a heterogeneous disease; some patients are going to come in with severe itching. Some patients are going to come in with really big spleens, so it just depends. But one of the things that really affects quality of life, I would say, is spleen size. Obviously just having a big spleen is not a big deal, it's all the things that come with it, right? So left upper quadrant pain, pain with eating, early satiety, nausea and vomiting, and then diarrhea depending on the size of the spleen. If a patient is eating less and then they have this disease that's also causing weight loss, weight loss might be a big factor for them. We focus on non-medical management at first: small frequent meals, adding in high caloric density food, things like avocados, nuts and peanut butter, milkshakes, nutritional supplements like Boost and Ensure. And then we make sure they have nausea medicines upfront, especially if we're starting medication. We'll make sure that they have a 5HT-3 antagonist on hand like ondansetron, and then depending on the severity, we might add in something else, like prochlorperazine or promethazine. If truly decreased appetite is the issue, then something like low-dose mirtazapine may be an option to help stimulate it. If there's diarrhea, then we need to talk about what the cause of the diarrhea is. Is it related to the drug or enlarged spleen?

I recently had a patient on momelotinib, and we initially thought the diarrhea was related to the drug, because it's a reported side effect and the timing seemed right, but she eventually was admitted because she was so cachectic and so malnourished, and it turns out she had overflow diarrhea from her hepatosplenomegaly compressing her bowel, so that's going to be treated differently than diarrhea from momelotinib. These patients are also immunocompromised, so diarrhea could be related to an underlying infection. Abdominal pain is tougher if it's truly spleen pain. Sometimes I have found some patients can do okay with a steroid, which might help the capsular stretching type pain just like with the liver. But we can also think about opioids, which would be really appropriate in these instances.

Sarah Profitt

Definitely. And I know for myelofibrosis patients in particular, another thing we want them to look out for are signs and symptoms of infection, especially if they're receiving a JAK inhibitor. Serious opportunistic infections, like viral or fungal infections, have been reported in clinical trials assessing JAK inhibitors, and I know, unfortunately, you and I have seen several serious opportunistic infections in our patients as well. So, it's always important to have the patient be monitoring themselves. We're certainly monitoring closely for signs and symptoms of infection as well and acting quickly to treat those if they unfortunately happen. Are there any other symptoms that you tend to spend a significant amount of time and effort on helping patients work through?

Kathryn E. Kennedy

Fatigue is a huge one. It's so tied to everything else, like if your nutrition is poor, your fatigue is going to be worse, and that may be because of splenomegaly. In general, fatigue is a tough one, and it's really impactful. If you want to go play 9 holes of golf, you're not going to be able to do that if you're taking 4-hour naps during the afternoon.

Sarah Profitt

Exactly. Cancer-related fatigue is tough to manage. It's probably under recognized. I think a lot of our patients might be dealing with this and not really know that it's abnormal or that we can help them with it. Like you said, there are a lot of factors that can be causing the fatigue. They can be disease-related factors, treatment related. They can be related to metabolic or electrolyte abnormalities, nutritional deficiencies like you mentioned. Thankfully, we have options to help patients manage this.

Low-intensity exercise has been shown in studies to improve fatigue. It's kind of counterintuitive to counsel a patient who's feeling fatigued how important it is for them to exert themselves even more, but it can really make an impact. There are pharmacologic solutions like low-dose stimulants, steroids, and antidepressants that have supporting data for managing fatigue. For patients who want more natural options instead of a prescribed medication, acupuncture, and supplements like ginseng have some data on managing fatigue as well. We tell our patients that if they are interested in trying any over-the-counter medications or dietary supplements, please contact us first so we can monitor for any possible drug interactions with their treatment. In clinic, I frequently provide recommendations on the potential risk versus benefit of these types of supportive care medications.

Kathryn E. Kennedy

Those are all great points. I think it is tempting to blame fatigue on the drug or the disease straight off. But it's important to remember that other things can cause fatigue, like hypothyroidism, B12 deficiency, etc. I will typically do a little bit of a workup and make sure their thyroid is normal, their vitamin D and B levels are relatively in line. We also have a great resource at Vanderbilt through our supportive care oncology group, which is embedded within our cancer center. They have great options for these patients, as far as like the ginseng, methylphenidate, and that those kinds of things that can help. And then other things like, you know, if it's anemia contributing, making sure we're a little more liberal with the transfusion parameters. Maybe this patient needs to be closer to 8 g/dL instead of 7 g/dL. I find that to be modestly helpful at times.

The other thing I see quite a bit is itching, and the most impactful thing for that in the long term is disease control. So it’s important to get them on a medication and manage all the side effects that come with that medication so the patient remains adherent to the treatment plan. Short term, sometimes things like steroids, antihistamines, doxepin, or aprepitant may all improve itching. Some medications that we also use for neuropathy, like gabapentin, can be helpful. I also will refer these patients to our palliative and symptom management team because they have good options for that. But again, disease control is really the biggest help.

Sarah Profitt

Absolutely. Thank you, Kate. That was such a nice overview of symptom management in our patients with myelofibrosis. And thanks for sharing about your experience helping patients navigate the diagnosis of myelofibrosis in clinic and what they can expect to experience as they undergo treatment for myelofibrosis and how impactful your role is as an APP in our clinic. I’m looking forward to our next conversation.

Kathryn E. Kennedy

Yes, thank you.