The Evolving Treatment Landscape in Myelofibrosis: An Advanced Practice Perspective

Kate Kennedy: Hi, welcome back to JADPRO's Roundtable discussion on myelofibrosis. My name's Kate Kennedy. I'm a nurse practitioner at Vanderbilt University Medical Center, specializing in malignant hematology and specifically myeloid disorders. I'm here with two colleagues. I'm going to let them introduce themselves.

Sarah Proffitt: Hi everyone. I'm Sarah Proffitt. I'm a clinical pharmacy specialist in adult malignant hematology at Vanderbilt University Medical Center.

Jill O'Brien: Hi, I'm Jill O'Brien. I'm a physician assistant at the Cleveland Clinic in Cleveland, Ohio, and I specialize in adult malignant disorders.

Kate Kennedy: Okay. So, for today, we're going to go through kind of diagnosis, prognosis, talking to patients, that kind of overview stuff. So, diagnosis, I find the hardest thing to do is just explain a really complicated diagnosis that is really way above the heads of a lot of practitioners and providers and physicians in terms the patient can understand. So, they don't understand why their spleen is getting big, they don't understand why their marrow is not working. I'll often frame this as just their scar tissue in the marrow for a variety of reasons, not going really into the pathophysiology behind that. That limits our body's ability to make the cells that they need to support our immune system. So, white blood cells, red blood cells, and platelets.

As that happens, our spleen and our liver try and take over some of that process to help support it, which causes that hepatosplenomegaly. And then, there's obviously a little bit of a difference between post-essential thrombocytosis, myelofibrosis, primary myelofibrosis and post-polycythemia vera myelofibrosis. Jill, do you find that that's an important part, an important distinction to make with patients when you're educating them?

Jill O'Brien: I try to make that distinction, but also keep it in terms that they can understand, especially as a provider talking with the patient. Patients are always trying to understand why do I have this disease? It's very difficult if it's not something that's passed down. So, if you can kind of give an underlying cause or at least allow them to see, "Oh, yeah, if you look at your platelet trend," it gives them maybe a little bit of an understanding of it, so they can at least understand maybe why they have the disorder.

Kate Kennedy: Yeah. So, prognosis is overall not fantastic with this disease, as we all know. There's a couple of different ways that we can measure that. So, for primary myelofibrosis, there's a DIPSS Plus score, which is a Dynamic International Prognostic Scoring System. What's interesting about this scale is that it's dynamic, so you can use it at any point during the treatments. You use it at diagnosis, and then you can use it 2 years later if you're seeing different things and you get a different DIPSS score that might tell you some different things.

It takes into account your age, white count hemoglobin, peripheral blood blasts, constitutional symptoms, karyotype info platelets, if you're red cell transfusion dependent, and then gives you a score somewhere between 0 and 6, with a median survival of 185 months for a score of zero, and then 16 months for a score of 6. And then, for primary and secondary myelofibrosis, we can use a couple of different scores. One is called a GIPSS score, which is a Genetic-Inspired Prognostic Scoring System. That only takes into account karyotype and certain molecular mutations. And then, a MIPSS70 Plus, which is a Mutation-Enhanced International Scoring System and adds constitutional systems, anemia, peripheral blood blasts to the karyotype in certain molecular mutations.

Jill, does your institute prefer one of those over the other?

Jill O'Brien: I feel like we use a combination of them. We'll show the patient the DIPSS and the MIPSS score. A lot of times, you will kind of end up in different categories. But I think it's a good way to show them that, especially they always want to know their prognosis and their survival. So, this allows you to talk to them that you can't give them an exact number that they would like, and you can see the variability amongst the different scores. Do you find that you prefer one over the other?

Kate Kennedy: We often will use the DIPSS score, but I think as time goes by, we're relying more on the MIPSS just because of the inclusion of the molecular data, which obviously has a big outcome difference.

Jill O'Brien: Sometimes I will just pull it up on the computer and kind show the patient so they understand what is being put into it.

Kate Kennedy: Yeah. I think it's also really important to include that this is incurable outside of stem cell transplant. So, that's something that we spend quite a bit of time focusing on in the beginning. And then, just kind of understanding what to expect. How many visits are you going to be, which will certainly depend on how severe your disease is at diagnosis. So, if you're somebody who's requiring red cell transfusions very frequently, you're going to be seeing me probably quite a bit more, and you're going to be spending quite a bit more time at the cancer center than you would if you're somebody who's been transfusion independent going into this. Symptom management, and that can be really difficult in this disease. What kind symptoms are you seeing most?

Jill O'Brien: I would say, probably splenomegaly, which they don't understand exactly what the symptoms are. So, I think to talk to them and be like, "Are you having trouble finishing a full meal? Do you just have some pain in there?" That seems to be one. They might have a decrease in their weight and fatigue.

Kate Kennedy: Yeah. I would say fatigue, splenomegaly and itching are the big ones that we see. And then, I think Sarah and I have both found this because I come to Sarah constantly with these questions, educating somebody on side effects up front or side effects to medications up front. So, depending on what we're starting them on as far as JAK inhibition, or which JAK inhibitor more specifically, what side effects we can see, kind of making sure that they have medications for those side effects so that they're prepared for nausea, vomiting, diarrhea, that kind of stuff up front to help them tolerate that medication is important.

And then, I would come to Sarah all the time with questions about time to response. So, when did the study evaluate response? Because these are not medications that work overnight, like our acute myeloid leukemia patients. So, it's really much more of a long haul than some of our other drugs. Sarah or Jill, what kind of things do you find that you need to really stress with patients in that situation, in an initial visit type of situation?

Sarah Proffitt: Kind of everything you've already mentioned. I think just empowering patients with digestible information is tough. You're trying to cover so much in that initial visit, but making sure patients know what to expect early on with a medication versus later on can also sometimes be helpful. Toxicities may be more common the first couple weeks or the first month that someone's taking a medication, and if a patient is aware of that ahead of time, they might be more likely to manage it aggressively, to be confident about staying on the medication versus being discouraged about the toxicity if they weren't aware.

So, I think, just kind of what you were saying, making sure patients understand the unique side effects of the medication they're starting, what to expect, how we can help them through it, and then kind of the timeline of when we expect it to occur and when we expect it hopefully to get better.

Kate Kennedy: The other thing I think is super important is just explaining to the patients when they should contact the team. So, we're giving them all of this information. We're like, "This drug can cause diarrhea, you can take Imodium. But when it gets to this point, I need to know about it." Which is always a hard one, I think, for people to entirely grasp. It's hard for me to explain.

And then, trials. So, like we talked about, we don't have effective disease modification outside of transplant. So, thinking about putting these patients on trials is really important because that could help us get to an effective disease modifying therapy. So, we'll often talk about what kind of trials we have available, what the meaning of a phase 1 versus a phase 2 versus a phase 3 is. I generally explain that as phase 1 is just looking at safety and side effects, disease response is not the main endpoint, but you might have some benefit from it. Phase 2 is does the treatment work? And then phase 3, is it better than what is already the standard of care?

It's also worth considering, if you don't have a trial, making sure that somebody else doesn't have a trial. There's clinicaltrials.gov that you can go to. I think that's especially important for community providers to know that that's available and that we do have clinical trials for these patients. So, even if the patient ultimately decides that they would rather go with standard of care, it's generally worth a referral to a tertiary center to make sure that there's not something that they would like to be a part of.

How do we talk to these patients about quality of life, especially going into what we know is likely a fatal disease? So, how is that something that you discuss with patients?

Jill O'Brien: So, I always let them know that obviously a transplant is the true cure. Being part of a transplant center like you guys are, I always refer to a transplant physician so they can at least have that initial encounter. They can talk to them about what a bone marrow transplant is, whether you think they're a candidate or not. And then, just having a discussion with the patient, what is important to you? Do you want a lot of office visits? Do you want to come frequently or is just more symptom management something that you're looking for?

Kate Kennedy: Yep. I find just making sure that everybody is on the same page is super important. So, if your whole goal is that you always want to play golf, then we need to rethink. The office visits that are every day are not probably in the cards for you.

There's also a significant financial toxicity that goes along with these drugs. Sarah, what kind of support do we have for those patients as far as financial toxicity, or what kind of resources do we have to direct them to if they just have questions about the disease and treatments or finding a myelofibrosis specialist?

Sarah Proffitt: Yeah, that's a huge part of managing diseases that we treat. So, we do have the MPN Research Foundation, which is a great organization. We work very closely with Leukemia and Lymphoma Society as well. They have a lot of educational resources for patients, patients' caregivers, even some support groups that patients can participate in to talk with other patients that are going through what they're going through as well. Manufacturers of the pharmaceuticals are immensely helpful. They have programs available to help patients with co-pays, uninsured patients can get assistance as well through the manufacturers. And they also have a lot of educational resources as well. So, luckily, we do have a lot of private and public organizations that are providing resources for our patients to help them through this.

Kate Kennedy: I found the Leukemia and Lymphoma Society, so it's great. The drug company will help us provide prescription assistance for the drugs, which are insanely expensive. But Leukemia and Lymphoma Society will also be really helpful for those patients traveling from a distance. They'll give them money for gas, that kind of stuff.

Okay. And then, the last thing that I just kind of wanted to quickly go over is just detail the roles of the care team. So, the physician, typically, at least in our practice, makes the diagnosis, assigns a prognostic score, discusses options with the patient in the context of the prognosis and age. For instance, in our transplant center, 75 is the absolute oldest they will do an allotransplant. So, if somebody gets diagnosed at 76, I don't refer them for consult.

And then, with the patient, decides on the most appropriate treatment and discusses the planned treatment with the PharmD to make sure that it's an appropriate thing that we can most likely get. Then I feel like the APP role, as far as NP or PA, executes the plan for disease management. We do a lot of symptom and side effect management, monitoring for response. We'll often alternate visits with the attending, or maybe I do two visits and then they do one visit, something like that. And then, obviously if I find something on their peripheral blood counts that looks abnormal, I'm going to them to discuss that with them. Jill, does that kind of sum up what your practice sounds like as well, or do you have other things?

Jill O'Brien: No, that pretty much aligns up with exactly how we do it.

Kate Kennedy: So, the RNs in our clinic, they're kind of our first line of defense. They triage messages and concerns. They can do some, increase fluid, take some Imodium, that kind of stuff through message baskets or phone calls. They're a huge help with care coordination, education, and then just emotional support. They're great at emotional support. What about in your clinic, Jill?

Jill O'Brien: Yeah. We have, the RN is definitely the first person that the patient will call and they'll get. So, they definitely develop a very good relationship with the patient. They're the ones that are fielding a lot of the questions and they're excellent with the emotional support.

Kate Kennedy: In our clinic, we have two different kind of pharmacists. So, we have the clinic pharmacist, which is what Sarah does for us, and then we have a specialty pharmacist. So, Sarah, do you want to talk a little bit about what the clinic pharmacist versus the specialty pharmacist does?

Sarah Proffitt: Sure. So, my role is primarily at the provider's side. So, we're talking about drug selection, which JAK inhibitor or other treatment is most appropriate for a patient, specifically if they have drug interaction concerns, organ impairment, overlapping toxicities with other comorbidities or medication, cytopenias at baseline; we're kind of talking through those clinical perils before someone starts treatment, and of course, helping provide recommendations for symptom management as well.

We do have a specialty pharmacy embedded in our organization, and they are wonderful helping us coordinate getting these medications actually in the patient's hands. So, they are experts in the financial toxicity management. They're helping us get grants, co-pay assistance, manufacturer assistance. They can help us with really difficult cases if we're working through insurance barriers or other access barriers to get patients on the therapy. So, can't say enough good things about having a specialty pharmacy as partners in our clinic.

Kate Kennedy: And then, we also use the MSLs as part of our care team. So, they're an employee of the drug company that's an expert in that particular drug. Sarah, have you had an instance, or can you tell us about an instance where you might've had to reach out to an MSL to help us with something?

Sarah Proffitt: Absolutely. They are super helpful when we need specific pieces of data or specific pieces of information. So, if I'm not able to find an answer to a question in the literature, they've been super helpful assisting us with managing dosing and monitoring of medications in the setting of renal or hepatic impairment. I've had MSLs assist me in answering specific questions about metabolism and pharmacokinetics if someone's switching from a clinical trial to a commercial medication, or vice versa, from a commercial medication to a clinical trial. So, they've been really, really helpful in my practice.

Kate Kennedy: We also have a social worker. She can help – in our clinic, it's a woman – but she generally helps get us the grants through the Leukemia and Lymphoma Society. We'll do a psychosocial assessment for pre-transplant, financial assessment, and patient and family assessment.

And then, I think probably the most important part of the care team is the patient. If they're not on board with the plan, we're not going to make any headway. So, it's important, I think, to involve them in the disease and the choice, and if there is a choice, to have that. I think that's everything. So, anything to add, anybody?

Okay. So, that concludes this discussion on educating and empowering patients with myelofibrosis. I'd like to thank Sarah and Jill for joining me. For more information and to view our other discussions on myelofibrosis, please visit jadpro.com.