Educated Patient® MPN Summit Diagnostics and Treatment Panel: May 7, 2022

This panel was moderated by Dr. Jamile Shammoand featured Dr. Aaron Gerds and Dr Bart Scott.

Shamo: Scott, in the past, no treatment was recommended, since it only addressed the symptomatology of (myelofibrosis [MF]). So what does the research today show about early treatment and slowing the progression of myelofibrosis?

Scott: Okay, so most of this data would come from the use of interferon therapy. And there are smaller studies, which we call phase 2 trials, showing that using interferon can reverse myelofibrosis. It can also cause molecular remission, but we don’t yet know if this translates to improved survival. This is therefore an important point. And then if you look at the COMFORT trials, yes, there was an improvement in survival with treatment with (Jakafi [ruxolitinib]), but this treatment was given to patients with intermediate to high risk disease. And there is no evidence that early treatment of low-risk patients with myelofibrosis with ruxolitinib, federatinib or (Vonjo [pacritinib]), one of the “ibs”, no evidence that early treatment improves overall survival. There is evidence that if patients need treatment, they have more intermediate-risk or high-risk conditions that may improve survival if treated with ruxolitinib.

Shamo: Thank you. And the next question is in this regard. I don’t have a genetic mutation and I have MF, can it still turn into acute leukemia.

Gerds: Certainly yes. So these modern panels, these gene panels that we have, check 60, maybe even 100, or some 100 genes, okay. So each of your cells contains more than 60,000 genes. And so we check a very small part of the genome. And some of these tests look at specific points within a gene, they may not look at the whole gene and its entirety. So it’s reasonable to think that for a lot of patients with quotes, triple negative, or myelofibrosis where the mutation isn’t found, there is a mutation somewhere that could lead to disease progressing over time. It is unclear what it may be and what kind of risk it is associated with.

Shamo: Thank you. Next question, I guess either one could take this, but that’s fine. Can you talk about iron deficiency anemia, I am on Jakafi and had phlebotomy in three years. I assume this is a PV patient, I am now taking iron supplements with a lot of fatigue which is not like me. So what does iron deficiency do to someone who may be on Jakafi?

Scott: To the right. Thus, the development of fatigue is a complicated problem in the field of MPNs. And there are several reasons why this could happen. And one of them is iron deficiency. So I didn’t talk about it for lack of time. But when you put a patient on cytoreduction, one of the goals of that cytoreductive treatment is to make sure that patients no longer need to undergo phlebotomy. And if you are able to do this successfully you may want to consider replenishing iron because iron deficiency can lead to high platelet count which you didn’t already want someone with implants it can cause fatigue, it can cause restless leg syndrome, and it can cause food puffiness. So in an ideal world, if you no longer need to receive about, and you’re on the spot, a reducing treatment, it would be nice to top up the iron.

But patients may have continued fatigue, despite adequate iron replacement. So one of the things that could be done is to assess the iron levels in an individual like this and make sure they’ve had adequate iron restoration. And if this happened, there may be other reasons for fatigue. And one of the things that can happen in patients with polycythemia vera is that they can progress to myelofibrosis, for example. So persistent fatigue, despite iron replacement, but a sign of progression of myelofibrosis. So it’s just something to consider the differential.

Shamo: I agree with that. And I guess I know there was talk about the NMP symptom assessment score and how we approach that. And I guess the question is, how do you calculate the contribution of NMPs to symptoms in someone who may have other comorbidities? So we always tend to be blamed and while patients have other comorbidities. How are you doing that?

Gerds: Well, for a lot of patients who may be inseparable, you know they’re different diseases, because unless you completely remove that disease from their body, you’ll never really know. We can get clues, okay. So if we say, you know, for example, use a JAK inhibitor, which we would expect to improve certain symptoms. And we see those symptoms getting better after starting a JAK inhibitor, well, then we can attribute those symptoms, at least that proportion of the symptom to the disease.

Likewise, when you stop a treatment and the symptoms return, that would also indicate that this is the source of that symptom. And you know, you think about other diseases and their treatment. Again, if somebody has sleep apnea, and that’s contributing to fatigue, once they start CPAP, or they have one of these new sleep apneas, pacemaker-type stuff cardiac, and his sleep apnea improves, well, and then his fatigue improves, well, then it was probably sleep apnea, if they fix the sleep apnea, and their fatigue doesn’t get any better than it would suggest again, going back to saying, well, maybe it was their MPN that caused this symptom all along. So really, it’s a bit of trial and error, in some cases, but it’s really hard to separate them because they’re all inside of one person. And unless you can completely rule out the disease, whether there was a full contributor, it’s really hard to know.

Shamo: I totally agree. Then, is there a direct causality between et and chronic migraine with aura?

Gerds: Oh, boy, I’ll choose that one. Um, again, you know, it seems like there’s an increased risk or patients are more likely to have headaches, whether it’s ocular migraines or some kind of migraine classic, there’s definitely that association there. And, you know, it tends to be something where you have to attack from both angles. So you need specific migraine therapy, whether it’s avoiding the triggers, you know, drugs like Imitrex, and that can help relieve migraines, as you know, dealing with aliens. So in ET we’ll be using things like aspirin for those microvascular disturbances as well as reducing the number of tries to improve those symptoms. So again, yes, they’re related, they’re connected. And often, however, we have to deal both ways.

Shamo: I am okay. And I think that ties into your previous point that we have to it’s kind of a trial and error that if you deal with an entity and say somebody’s platelet count is optimized, and they continue to have a migraine, well, then you have to treat the migraine etc.

Next is for Dr. Scott, can we take a break from medication when we take hydroxyurea for PV, and can we take some time off medication to give our bodies a rest.

Scott: I generally don’t recommend it due to concerns about proliferation and the risk of thrombotic complications. Thrombosis is the leading cause of death for patients with polycythemia vera, and maintaining a hematocrit below 45, white count below 11,000, and platelet count below 600,000 is an important of this treatment. So I would say that if there are issues with the administration of hydroxyurea and the patient has symptoms, a better way to address that issue is to consider other types of therapeutic interventions. And Jakafi is FDA approved for patients whose second line treatment, if they fail, are hydroxyurea intolerant, and as I mentioned the proud PD trial showed a composite endpoint similar over 12 months with CHR and reduced spleen size comparing online pegylated interferon to hydroxyurea so people have problems with hydroxyurea a better way to approach what is considered as different therapeutic treatments, rather than stopping the treatment.

Shamo: I totally agree. So why don’t we have some final thoughts from Dr. Gerds and Dr. Scott, before we wrap up, and then maybe we can take a break after that? Let’s start with Dr. Gerds.

Gerds: Thank you. Thank you very much again, you know, thank you all for tuning in. And, you know, learning about your disease, you know, those things are incredibly complicated. And there are so many things that influence how an individual can feel and how their journey can unfold. So I think, you know, kind of the takeaway here, everyone’s background and background can be different. And really developing a relationship with your healthcare providers, your doctors, your nurses, and your nurse practitioners is really important. This way you get the best treatment possible based on what is going on with you at the time. So I know there are a lot of good discussions to come and new things to come. So I’m sure that the continuation of the talks will be very exciting.

Scott: Thank you. I would like to thank all the patients who have contributed to our understanding of this disease, and participation in a clinical trial is always an option for your care.

Raw transcripts have been lightly edited for clarity.

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