The Evolving Treatment Landscape in Myelofibrosis: An Advanced Practice Perspective

Jill O'Brien: Welcome back to JADPRO's Roundtable discussion on myelofibrosis. I'm Jill O'Brien. I'm a physician assistant in hematologic malignancies at the Cleveland Clinic, in Cleveland, Ohio, and I have Kate with me.

Kate Kennedy: Hi, my name's Kate Kennedy. I'm a nurse practitioner at Vanderbilt University Medical Center. I specialize in malignant hematology, specifically myeloid neoplasms. And Sarah.

Sarah Profitt: I'm Sarah Profitt. I'm an adult hematologic malignancies specialist. I am a pharmacist here at Vanderbilt University Medical Center, working with Kate.

Jill O'Brien: Hi. Thanks everybody for joining me. So I am going to tie in the other two videos that we've done. And while it's nice, we learned about all of the JAK inhibitors and when you would use them, but as I'm sure you both know, patient care and patients present differently. So I just wanted to walk through two different case studies and I thought we could talk about how the different ways that we could have treated the patient and what our different options are.

All right, so my first case study, I will start with a 76-year-old male. So he presented to the clinic with complaints of fatigue, weight loss, and abdominal fullness. On physical exam, it was found that he had splenomegaly, with 12 cm below the costal margin, so a very enlarged spleen. His lab work showed a white count of 9.5. It did have 3% blasts on the diff.

His hemoglobin was 10.5 and platelets were 181. So obviously, this was concerning for the practitioner that the patient was seeing. So he had the patient undergo a bone marrow biopsy, which showed 90% cellular marrow, with myeloid expansion, dysplastic megakaryocytes and clusters, myelofibrosis 3, with 5% myeloid blasts. He did have normal cytogenetics and his NGS panel was positive for the JAK2 V617 and ASXL1.

So he was diagnosed with primary myelofibrosis and then this physician referred him to a specialist that manages myelofibrosis. So when he initially met with this specialist, they did run his risk score. So on the DIPSS score, he had an intermediate-2 risk, and on the MIPSS he had a high risk. So during that initial discussion, the provider spoke to the patient. So the male, the patient was 76, so he was on the older side for a bone marrow transplant.

And actually, after talking to the patient, it was determined that he actually wasn't interested in that at all and that his primary goals of his care was to focus on his quality of life, specifically spending time with his family. So he did mention he didn't want to come to the clinic for a lot of visits.

They did evaluate if he was eligible for a clinical trial, but it was determined that he wasn't eligible for one. So Kate, if this patient presented to your clinic, what would the options be that you would consider treating this patient with?

Kate Kennedy: So with this patient who has a relatively okay hemoglobin, 10.5 normal platelets, rux and fedratinib, ruxolitinib and fedratinib are both good options in this patient.

Jill O'Brien: So that's what the provider spoke to the patient about his different options and they decided that he would start on ruxolitinib, 15 mg, twice a day. So the provider had the patient get lab works twice a month and follow up every month while he was starting this treatment to ensure that his symptoms improved. So initially, his symptoms did improve, his spleen volume decreased. The patient noticed that he was able to eat meals better, he didn't have as much discomfort, and his weight actually increased.

He continued then to have just monthly lab checks to ensure that everything was going okay. And about 6 to 8 months into his treatment, on the routine lab work, the provider noticed that his hemoglobin was down to 8.5 and it had slowly started decreasing. At the next provider visit, he was asking the overall symptom questions to the patient and it came out that the patient did endorse. He was having worsening fatigue, almost back to where it was when he presented. He was having to take more naps during the day, which was abnormal for him and that, just he felt more short of breath. The patient said that he helps watch his grandchildren and he was finding that he was more short of breath when he was playing with them throughout the day. So Sarah, at this point, what are your options that you could consider? It seems that this patient's having some symptomatic anemia, so what would you consider?

Sarah Profitt: Yeah, this is unfortunately something that does happen while patients are receiving JAK inhibitors. Cytopenias can become problematic. And even if someone is not requiring transfusions, they can still be symptomatic from anemia. It sounds like this patient certainly was experiencing symptomatic anemia. There're a few options.

Hematologic toxicities with ruxolitinib can be dose dependent. It's possible that there's a slightly lower dose of ruxolitinib that would control symptoms but allow his blood counts to improve. Could certainly be a first step going down from the 15 mg, twice a day, to 10 or even 5. We luckily have room to titrate ruxolitinib.

Luckily, there there's some other options we could consider as well to manage anemia. We could check an EPO level. Think about erythro-stimulating agents, ESAs. We could think about luspatercept and that on to the JAK inhibitor. Danazol is another medication we commonly use to manage anemia for patients with myelofibrosis. We could also just consider switching the JAK inhibitor to one that may not cause as much anemia. Luckily, there are some options we could consider for this patient.

Jill O'Brien: So after the provider spoke to the patient, it was clear that this was affecting his quality of life. They talked about checking EPO levels, adding one of those agents. But the patient just really wanted to try something else. He really just wanted to focus on his quality of life. So the provider switched him to momelotinib, because you should still have the same symptom management, but see the increase in the hemoglobin and get some benefit with the anemia.

So he switched him to momelotinib. The patient tolerated it fine. He had some GI upset at first, but that was quickly managed with Imodium, as needed, and resolved after a little bit. And then at his 2 to 3-month follow-up, his hemoglobin had improved a ton and the patient was saying that he was enjoying his quality of life again, and he was happy that he didn't have to come to the clinic as frequently. So Sarah and Kate, is there anything different that you would've done or you would've thought about differently with this patient?

Kate Kennedy: No, I don't think so. I think that's a really reasonable thing to do. Momelotinib has a lot of the benefits as the ruxolitinib. I mean, the same benefits as the ruxolitinib, but with the added increasing the anemia, which seems to have really been affecting his quality of life. So I don't think there's anything I would've done differently with that. I'm impressed that he had such an improvement in his hemoglobin at the 2-month mark. I feel like it can often take a lot longer than that. So that's exciting for him.

Sarah Profitt: Yeah, nothing to add.

Jill O'Brien: All right. So I will get to my next case study, which this one is a little more difficult. I'll talk about some drugs that were used a little off-label, but there have been studies to show some benefit with it. So I will start. So we have a 63-year-old female. She has no significant past medical history. She presented to her local emergency room with just complaints of left upper-quadrant abdominal pain that was worsening and not getting better. So while in the ED, they performed a CT abdomen and pelvis, with IV contrast, and she was actually found to have a 25 cm-enlarged spleen. On her lab work, she was found to have a white count of 91. So given this, the emergency team admitted her to the hospital because, obviously, there's a concern for some sort of hematologic malignancy going on.

So when she was admitted to the hospital, she underwent a bone marrow biopsy to figure out the diagnosis, which again showed a hypercellular bone marrow with 2% blasts. She was diagnosed with primary myelofibrosis. They ran the DIPSS and the MIPSS score. So on the DIPSS she had intermediate-2, and on MIPSS she was high risk. So at this local hospital, their initial treatment was Hydrea, because that can lower the white count.

So she was discharged on Hydrea, with a quick follow-up to a hematologist-oncologist at a tertiary care center that specializes more in myelofibrosis. So when this patient saw that provider, her white blood cells had returned to an acceptable level. So they stopped the Hydrea and the provider then started her on a JAK inhibitor. So Sarah, what JAK inhibitor would you think about for this patient that was on Hydrea, had their counts returned to a normal level?

Sarah Profitt: Yeah, good question. If the counts are normal, luckily we have several options available to us. You could consider ruxolitinib, fedratinib, Again, if baseline cytopenias aren't an issue, we expect symptom improvement with both of those medications. If the Hydrea had affected the platelets or if the disease process had affected the platelets, we could think about starting with pacritinib for her if she had thrombocytopenia.

Jill O'Brien: So all of those things are what the provider obviously went through in their wheelhouse When they were thinking of what to treat, the first thing was they did discuss a clinical trial with the patient. She did live a little distance from the clinic, so she just was concerned about the time it would take to come for all of the appointments. So given that the patients platelets were normal, the providers started them on ruxolitinib, 15 mg, twice a day. They explained that this improves her debilitating symptoms that she was experiencing. She was still having the splenomegaly, still having pain from it. It doesn't treat the myelofibrosis. So she was started on the – it doesn't cure, I should say it does treat, but it treats the symptoms, it doesn't cure it. So she was started on 15 mg of rux, and then she continued to have splenomegaly and pain at subsequent visits. So Sarah, could we dose increase her?

Sarah Profitt: Yeah, you could consider going up on the dose, but I think if patients are still experiencing disease symptoms or aren't able to be treated on that dose, maybe switching medication would be an option as well.

Jill O'Brien: Yeah. So this provider did decide just to uptitrate the dose. They went up to 20 mg BID and it actually improved the patient's symptoms. But she then, at another office visit, had profound leukocytosis. So Kate, if you were seeing this patient in the clinic for your APP visit, there's a big jump in their white count, would you be concerned about something?

Kate Kennedy: Yeah. I'd be concerned about a lot of things, but I think I'd be most concerned about just what does that mean? Does she have a progression to something like a AML from her disease? Is there a lot of circulating glass? What does the diff look like? Regardless, being on a high dose of rux, that high of a dose of rux and then having that white count speaks to the aggression of her disease. So we've got to do something, and I think her age would allow her to go for a transplant consultation.

Jill O'Brien: You're exactly right, given the profound leukocytosis. Luckily, she did not have a large amount of circulating blasts in her periphery, but there was just concern of the aggression of this disease and that it could quickly progress to an acute leukemia. So the provider wanted to have some cytoreduction, so they started her on a combo pill of decitabine and cedazuridine, which is actually an off-label use for aggressive myelofibrosis. Typically, this medication is used to treat MDS and CMML. Have you seen this used in your practice with myelofibrosis to obtain cytoreduction?

Kate Kennedy: Yeah, I think we've used it specifically in accelerated phase or obviously, like AML from myelofibrosis, but certainly with accelerated phase.

Jill O'Brien: Yeah. So this patient, this is actually, I'm not making this up, but yes, this patient really had a lot going on, because it did exactly what it was supposed to, but it dropped her too low. So we actually held all medications, allowed her counts to recover, her bone marrow to recover, and started her back on ruxolitinib, 15 mg, twice a day. And during that whole time period, she also was meeting with our bone marrow transplant team. She was being worked up for a transplant. She was deemed a candidate. And once her counts were stable, her symptoms were stable, we actually got her to transplant quickly and she underwent an allogeneic stem cell transplant, which as you know, is the only true cure for myelofibrosis.

That was a very complicated and roundabout case study. And I feel like at different points, you could've gone with different treatments. Do you guys have any input on it, things that you would've definitely done differently?

Kate Kennedy: I don't think I would've done anything differently. I think potentially, the only thing is maybe instead of increasing rux, we could've chosen a different, but that is so much more the art than the science of medicine. I think that's a perfectly appropriate thing to do.

Jill O'Brien: Yeah. No, I was wondering that too. If perhaps could we have slowed down the progression or would it have progressed if we would've tried a different JAK inhibitor? It's tough to say.

Kate Kennedy: Yeah.

Jill O'Brien: So I just wanted to bring up these two case studies, because I think it does obviously tie in the first two videos. One, it talks about the different medications that we use, but I think it also ties in the second video really well. The provider spoke to the first patient. He was clearly very vocal in what he had wanted and what his hopes for being diagnosed with myelofibrosis was.

And having this good two-way communication street allowed the provider to land on a treatment that worked best for the patient. Momelotinib was the best one. It helped his anemia and it helped manage his symptoms, and he didn't have to see us a ton.

And then the second one, I think, just demonstrated the aggressive nature of myelofibrosis, which sometimes, I think, we can forget about how aggressive this disease can be. And what I didn't mention in the study was we were able to follow her counts so closely.

And by having these provider visits alternating between an APP every two visits and a physician, we're able to stay on track of how she was doing, how her symptoms were doing, and what her counts were doing, which I think allowed us to act quite quickly when we noticed these abnormalities in her blood counts. So I think that speaks to how the APP and the physician can function together very well. Do you see this similarly happening in your practice?

Kate Kennedy: Definitely so. I think the care coordination between either us and the patient's outlying hematology provider, if it's somebody, like they're maybe going locally for count checks or the care coordination that's happening between APPs and the physicians at the tertiary care center, yes, definitely so.

Jill O'Brien: And definitely the pharmacist, when we're using medications off-label, the pharmacists help us to get it approved by the insurance company. So I think the second case wouldn't have been able to get everything accomplished so fast without all members of the team acting and working together.

This concludes our discussion of case studies and clinical applications and myelofibrosis. I'd like to thank Kate and Sarah for joining me. For more information and to view our other discussions on myelofibrosis, please visit jadpro.com.