Role of Symptom Burden in Thrombocythemia and Polycythemia Vera

Shared insight on how a patient’s symptom burden can impact management strategies within essential thrombocytopenia and polycythemia vera.


Naveen Pemmaraju, MD: For both of you, before we move on, Ruben, you’ve been the pioneer, the driver behind the MPN [myeloproliferative neoplasm] symptom burden, and this is becoming more important, not only in myelofibrosis, which we’ll discuss later, but as you and your group have shown, in PV [polycythemia vera] and ET [essential thrombocythemia], where patients’ symptoms may be out of proportion to their blood counts. Ruben, if you can comment on the symptom burden and its importance, particularly in clinical trials and drug development.

Ruben Mesa, MD: In PV and ET, it really gets to what are the goals of therapy. Historically, our field has focused solely on preventing thrombotic events and bleeding to some degree, kind of irrespective of how the patients felt. While working with patients and patient groups, it was very clear—we did symptom research, but I’ll give credit where credit is due—the patients [who] called out to say, “We are symptomatic. Help us tell this story.” They encouraged us to do this. It’s given us a lot of insight. They can be heavily symptomatic, and it clearly can have biological underpinnings. In PV and ET, there can be vascular-related symptoms that are short of thrombosis. Thrombosis is the extreme end of circulation not working well. We have cognitive impairment, kind of a chemo-brain sort of phenomenon, difficult headaches, complex migraines, and so on, in addition to other cytokine-driven pieces. For the [patient with ET or PV], your goal is to make that disease as invisible in their life as possible. If you’re not, then something needs to change. [Decreasing] the risk of thrombosis and bleeding is great, but you may have severe migraines that cause you to vomit weekly, or have pruritis that you cannot sleep 3 nights out of 7. Some patients have severe [adverse effects] that can occur with these diseases, so the symptoms assessment tools are helpful for quantifying that. Patients are usually telling you this, but you can quantify that. It can be an indication for therapy, but also adjustment of dose. If you started them on hydroxyurea to improve their symptoms and you’ve decreased their plate account from a million to 800,000 and they still have symptoms, you’ve not achieved your goal. It can be helpful in terms of initiation and dose, and it can be helpful in terms of deciding to change therapy. If I have a patient with PV and they’re on hydroxyurea or interferon and they need fewer phlebotomies, but they still feel terrible related to their disease, that can be a strong indication for considering ruxolitinib as a second line and particularly beneficial for those symptoms. It’s an additional decision-making tool. It’s not all about symptoms, but they’re important and needs to be balanced against that other piece, which is vascular event prophylaxis.

Naveen Pemmaraju, MD: That’s wonderful. Before I move on from that, Dr Palmer, in terms of the symptom burden, you’ve been a passionate advocate for a patient-centered approach. I’d like to get your thoughts on the evolution of the symptom burden. I remember you showed a slide once of how much the symptom burden scale has changed over time. What are your comments on this important issue?

Jeanne M. Palmer, MD: The symptom burden is interesting and something that is important to patients. It’s something that I monitor every time I see them in a systematic fashion. The initial iteration of it had far more symptoms associated with it, and over time, it has fortunately become smaller and smaller in terms of the number of symptoms that we need to collect. Even more interesting is the information of what is a significant change in the symptom burden and what constitutes something meaningful for the patient. That’s something that I still think is being assessed in research, but it’s something I look forward to seeing.

Naveen Pemmaraju, MD: That’s just wonderful. Again, before we leave this topic, Dr Stephen Oh, you’ve done some of the pioneering work in our field in terms of inflammation, cytokines, NF-κB pathways, would you care to give some comments about symptom burden, cytokines, and all the work your lab has done?

Stephen Oh, MD, PhD: Both from the clinical data and experience in patients with PV and ET, and from the work that we’ve done and many others in the field, it’s clear that inflammation is an overarching theme driving these diseases and symptoms in these patients, whether we’re talking about myelofibrosis, PV, or ET. In particular, we’ve had some discussion about how patients with PV and ET can have bothersome symptoms, and while the focus for many years has been almost entirely on prevention of thrombosis, all are appreciating and thinking about how to ameliorate those symptoms. I’ll highlight in particular itching, because in some patients it’s a disabling symptom. That is something where patients often become accustomed to dealing with that and they don’t tell you as a treating physician unless you specifically ask about it. They can’t take a hot shower, they must take Benadryl, etc. That is something that is becoming clearer, especially if you ask specifically about it. With the current state of affairs, with treatment options for PV and NET, in the PV setting we now have a bit of a dichotomy because for those patients who have severe symptoms, ruxolitinib is very effective. I have patients [whose] severe itching completely goes away because of ruxolitinib, which is important and meaningful for those patients. You have ropeginterferon, which is FDA approved. It’s a little bit of an apples to oranges discussion as to what are the problems, what are the goals for the treatment, and what’s the expectation in terms of [adverse] effects? More and more we all must be comfortable tailoring the specific treatment choice to the individual patient.

Transcript edited for clarity.

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