What Advanced Practitioners Need to Know about Myelofibrosis

Julie Huynh-Lu: Welcome to part 2 of our round table discussion on myelofibrosis. My name is Julie Huynh-Lu, and I'm back with my colleagues Lindsey Lyle and Maureen Thyne. Lindsey and Maureen, thank you for joining me today. In the first part of our discussion, we talked a little bit about the pathophysiology, how these patients present, how we diagnose them, and how we determine their risk features. The next group of discussions that I wanted to talk about is the features of this disease and how it impacts our patients' quality of life and their overall survival, and of course, discussing treatment goals and personalizing these treatment goals for our individual patients. Lindsey, if you don't mind guiding us through how this disease presents and the impact it has on our patients and their quality of life.

Lindsey Lyle: Absolutely, and thanks, Julie. As we mentioned in the first video, as Maureen so nicely did really give a good idea of how these patients can present, no two patients are the same. A patient may have debilitating symptoms, another patient may be relatively asymptomatic, a patient may be extremely anemic, and the other with a very normal looking hemoglobin, just for some examples. But as we're learning over time to understand these different clinical features of the disease that we do know are markers of the disease itself and really trying to understand how they impact our patients' quality of life, and also survival, as you mentioned.

The spleen is quite large, generally speaking. It's a marker of the disease process and it is the primary endpoint for all of the therapies we're going to be talking about as far as a treatment goal. And so, there have been a number of publications looking at patients who achieved different degrees of spleen volume response. In a pooled analysis of overall survival in the COMFORT-I and COMFORT-II trials, which were the trials evaluating ruxolitinib in the front-line setting, these showed that spleen volume reduction did impact overall survival. Interestingly enough, also looking at pooled analysis of patients treated with pacritinib on the PERSIST-2 trial, they also found that spleen volume response was predictive of overall survival in patients with myelofibrosis who were treated on pacritinib. Interestingly in this study, this did not occur in patients who were treated on the best available therapy arm.

But we know that spleen volume reduction is important and all of us in practice know that this is important from a quality of life perspective. Great, we can really help our patients feel better. We can help them gain weight by shrinking their spleen. We can reduce some vascular congestion in the abdomen, which, ultimately, will behoove our patients. But also noting that this is pretty important as there's this overall survival correlation. So important to keep in mind.

Also looking at disease-related anemia and impact on overall survival, this was shown to impact survival. Patients who are transfusion-dependent tend to have worse overall survival. And this is also reflected in our prognostic scoring system that you so nicely went through. This does affect our patients' quality of life for a number of different reasons. Time in the chair, this is a very basic thing, but it takes time to get blood, and especially if you're not in a large academic center, this may not be done the same day. This may be done in an emergency room. A lot of different things can really impact the patients' quality of life as it relates to just the simple process of getting blood. The potential burden on a caregiver that may have to take them to give blood, risk for iron overload. These are all things that we need to take into consideration, especially in our patients who are heavily transfusion-dependent.

We can't un-marry these two, survival and quality of life. It's interesting because if we think about what's more important to patients, I bet they would say both, but what they're living with is right now, so we have to also, too, remember that quality is really, really important. Thrombocytopenia also correlates with overall survival, with the most difference being in patients who have platelets < 50,000.

So these are three key clinical features that may affect our patients with myelofibrosis that I think the advanced practitioner should really be aware of from a broader view of not only symptoms and management challenges, but also overall survival. And ultimately, Julie, we are here to change the outcome for these patients as our mentor has always said. So moving on to treatment goals, Maureen, I would love for you to talk with us through how you approach these conversations with patients and what are your personal goals from the fact that you've been doing this for a very long time.

Maureen Thyne: Thanks Lindsey. What's so interesting, I think you guys will agree, is that the quality of life and all the things you just mentioned, spleen, anemia, quality of life, these are such repetitive topics that we'll talk about, not just to each other and to our colleagues, but to our patients. And they feature so heavily also in our treatment goals. So I think what I'm about to say is going to sound very familiar to what you've just heard Lindsey talk about, just with a slightly different spin. So all of the things that become things that we are aiming to make better with our treatments are because we're trying to improve patients' overall survival.

Without further ado, our goals in making patients' lives better and lives longer involves trying to reduce their risk and reduce their incidence of transforming to something worse, like leukemia, for example. We're trying to mitigate the risk for things like thrombosis or bleeding or infection, things that they are at risk for because their blood counts are either too low or too high, because as you heard earlier, they can run the risk of having either of those things because their counts might be mismatched or might be low or high because this is a disease that's just not universal.

So quality of life, again, just features so heavily in our treatment goals. We're trying to make our patients' lives better by making their symptoms better or making their anemia better or making some feature of their disease better. One of the reasons that we are so much more acutely aware of this is after the Landmark study was conducted, which was a survey of both patients and providers who treat myeloproliferative neoplasms including myelofibrosis, it featured looking at patients who reported in about their symptoms with myelofibrosis. And one of the things that was so revealing was that so many more patients were symptomatic of their disease. For example, more than 80% of patients strongly or somewhat agreed that their quality of life was reduced because of their myelofibrosis specifically, which was overwhelming to providers. We didn't fully appreciate that so many of our patients were so significantly symptomatic, and it could have been from anything. Fatigue happens to be the most common symptom, and we haven't even talked about that specifically yet.

So our goal is to reduce their symptom burden and possibly their splenomegaly. We haven't so much talked about the specifics of splenomegaly yet, but splenomegaly also has a bunch of downstream symptoms that come from that abdominal pain, the reduction of appetite, etc. Fatigue, which I just mentioned, also has a bunch of downstream symptoms that come from that. Not being able to get around and move, having a reduction of work hours, a reduction of interaction with family and friends. And of course anemia, as Lindsey talked about, also can cause fatigue. So we have a lot of these external factors that can kind of interplay with each other, so trying to improve their fatigue and their anemia, and we'll talk a lot more about anemia as we talk about some of these specific treatments that we have available. I don't know, Julie, if you want to maybe kick us off with some of the specific treatments. We have a couple to go through.

Julie Huynh-Lu: Yes, we do. What's crazy is when I first started in the MPN world, really, ruxolitinib was the only one around. And then over the course of just the last few years, we've gotten fedratinib and pacritinib and momelotinib, so the treatment landscape has changed quite a bit and it's just so gratifying to see because there's more that we can do for these patients than what we had before, which is wonderful.

I'm sure y'all are well aware that ruxolitinib was the first one to be approved. It's a JAK1/JAK2 inhibitor. It's for intermediate, high-risk primary MF or secondary myelofibrosis. And then, of course fedratinib, which was approved in 2019, so almost a decade later before there was any movement in the MPN treatment category. It's a JAK2/FLT3 inhibitor, and it's also approved for intermediate-2 or high-risk primary or secondary myelofibrosis.

And then, of course, we have pacritinib, which is very helpful in patients who have low platelets, which, as you guys are well aware, patients who are now starting to live longer just because what we have available to treat them with, now their diseases are starting to be able to progress to a point where their platelets are getting lower or maybe they already had high-risk disease and have low platelets, and before we had nothing to give them or offer them. And now this is a potential medication we could. This is approved for patients with platelets < 50. Momelotinib, which just got approved last month, is a JAK1/JAK2/ACVR1 inhibitor, which we briefly mentioned in the first video in regards to hepcidin. It's approved for patients with intermediate or high-risk primary or secondary myelofibrosis with anemia.

So there's just a whole slew of JAK inhibitors that can be helpful in terms of improving constitutional symptoms and splenomegaly, because as we all know, all the treatment options we have is really geared toward improving quality of life, improving symptoms, and nothing curative, unfortunately, that we found just yet. And the only cure at this point is a transplant. Maureen or Lindsay, what do you do when a patient has a very proliferative disease? And even if they're on a JAK inhibitor, what other options would their potentially be to add on to a JAK inhibitor, potentially?

Lindsey Lyle: I think this can be a challenging patient population, but certainly there were some therapies that preceded these JAK inhibitors and obviously didn't really make a huge difference from a symptom spleen perspective. But sometimes we may layer on hydroxyurea to help with these very proliferative patients. Outside of that, I suppose it just depends on how they're looking. Are they progressing to a time blast phase? Are we adding a hypomethylating agent? I think these are certainly all considerations.

One thing that we didn't talk about too is interferons. Now, certainly used more so in other MPNs, but there is some interesting data in this pre-fibrotic myelofibrosis patient who may not have such dramatic features of disease. So just a lot of interesting things, as you mentioned. Maureen, any other thoughts?

Maureen Thyne: Well, I'll make a small plug for the use of interferon as a representative of the institution that's basically done all the interferon research. It is the only medication out there shown to reverse fibrosis in the marrow. So we are still using it, we are layering it on with some of the JAK inhibitors. And so for your proliferative patients, it actually might be a decent option, but it's certainly not as heavily used as the options that Lindsey has mentioned.

Lindsey Lyle: Right. But we can get in these sticky situations. So you're exactly right, Maureen, and just like Julie mentioned about patients with low platelets, we get into these tough situations and there's certainly data to support these combinations while not specifically approved.

Maureen Thyne: You have to get creative.

Lindsey Lyle: You do have to get creative. Exactly. I was just thinking too, talking about sticky situations in our patients who develop anemia, as Julie mentioned, momelotinib now approved for patients with myelofibrosis and anemia, pacritinib also showing some benefit from an anemia perspective in their data. So now we have some options from a JAK inhibitor perspective, and also some supportive care options that maybe we're more familiar with because we've been utilizing longer. Anything that either of you found particularly helpful?

Julie Huynh-Lu: We use Procrit-Aranesp. We've actually been able to get luspatercept for a few patients, which has helped. There's a few that we've put on thalidomide to assist with anemia as well, and of course danazol. Maureen, anything different from your end?

Maureen Thyne: Yes, we've done the same. ESAs, for sure. We've had some success with luspatercept, for sure. We've been using the IMiDs for a while as well, layering that on too. And although we don't use a lot of danazol, we have a few patients on it. I'm excited to get the ball rolling with more momelotinib. 

Julie Huynh-Lu: I really wish we had more time to discuss because there's just so much information that needs to be had about all these different therapeutic options, but unfortunately, this brings us to the end of this part of the discussion. Lindsey, Maureen, thank you so much for taking the time to talk with me today. Again, for any more information or to view our other discussions on myelofibrosis, please visit JADPRO online at JADPRO.com. Thank you so much and have a great day.