Failure of Polycythemia Vera Control with Phlebotomy

Transcript:

Srdan Verstovsek, MD, PhD: Polycythemia vera is a condition where the red blood cells grow way out of control. That utilizes iron, and the PV patients become iron deficient. It is not wise, typically, to supplement the iron in patients with polycythemia vera, because that would make red blood cells grow faster. Then you need more phlebotomy or, in case of a patient who is also on hydroxyurea, that would compromise the utility of cytoreductive therapy. Hydroxyurea would control the blood cell count, in general, in patients with polycythemia vera by not allowing cells to grow too fast. It’s a chemotherapy. It kills cells that grow, but it does not do anything about the iron levels.

Contrary to that, the JAK inhibitor, ruxolitinib, has been shown to control the blood cell count and improve symptoms related to the disease, as well as the iron levels in the body of the patient. So, by unknown mechanisms, as of yet, the iron levels in patients on ruxolitinib improve to normal levels within 3 months, which should improve their cognitive ability and any other side effects from having low iron. In that case, I’m quite surprised of the multiple benefits of ruxolitinib that are being discovered as we treat patients with polycythemia vera. Beyond just controlling the blood cell counts, symptoms, and iron levels, it’s an overall change in the management of polycythemia vera patients.

Ruben Mesa, MD: Patients with high symptom burdens in polycythemia vera represent about half of that population. Our group has been very engaged in trying to quantify the symptom burden in these patients, whether it’s fatigue, night sweats, itching vascular symptoms, etc. This could be a very difficult group, and it could be very difficult to improve those symptoms. We’re mindful that many of our therapies in the past have had some impact. A control of phlebotomies, of the erythrocytosis, helps to improve, to some degree, some of those symptoms. Aspirin can sometimes help with some of those symptoms. Hydroxyurea can sometimes help with some of those symptoms. But, so many symptoms can remain, and there are times when some symptoms don’t respond at all.

The availability of ruxolitinib has been very impactful for that symptomatic profile, in particular with symptoms that have not responded to the other interventions—pruritus, fatigue, night sweats. In addition, it’s helpful in its ability to control counts in patients who have failed hydroxyurea, and to control the related symptoms such as headaches, arthromyalgia, and others. The typical arc of patients with polycythemia vera who are well-controlled on phlebotomy and aspirin alone requires several phlebotomies at the time of diagnosis and soon thereafter, but relatively quickly—within a few months—they fall into a pattern of needing very intermittent phlebotomies, 1 every few months.

Those who don’t fall in that pattern and need continued phlebotomies are patients whom we now have on hydroxyurea. If they continue to need phlebotomies in that setting, we know that they don’t tolerate it very well, and that’s for several reasons. That can include iron deficiency. That can include difficulties on the veins and the hassle of needing to receive the phlebotomies. Indeed, iron deficiency helps to control erythrocytosis, but iron deficiency has its own symptomatic burden that comes with it; this has been well documented. We even know, from studies with teenage girls who have iron deficiency from menstrual blood loss, that they clearly have a variety of negative impacts from that iron deficiency. The difficulty with patients with polycythemia vera is that in the absence of proper cytoreductive therapy, we have really no way of correcting the iron deficiency. If we take the phlebotomized patient and give them iron, we’re going to end up phlebotomizing them further.

Transcript Edited for Clarity