Therapeutic Options for Polycythemia Vera

Transcript:

Srdan Verstovsek, MD, PhD: The 2 basic factors that we utilize in everyday practice to assess the risk of blood clot in patients with PV [polycythemia vera] are an age over 60 or a history of blood clot. If one or the other is present, then that patient is really in need of something more than phlebotomy and aspirin (to decrease the risk of blood clotting).

Traditionally, the first 2 choices that you have—equally level in the guidelines—are hydroxyurea or interferon. In everyday practice, my impression in the United States is that most of the patients are given hydroxyurea. It’s an oral chemotherapy agent, which aims to decrease the blood cell count and eliminate the need for phlebotomy. So, one would start with 1 pill a day, usually, and titrate up or down (based on the need to control the blood cell count), with a goal to have hematocrit below 45%. As an alternative, in some patients—particularly, younger patients whom we do not want to be exposed to chemotherapy for the first time in their life, or in women who would like to become pregnant—because chemotherapy can cause harm, interferon is preferred. So, there are patients who are actually given, in everyday practice, interferon. This is a biological agent. Usually, it’s injectable under the skin, administered once a week. It is an established mode of therapy, as well.

Jamile M. Shammo, MD: Prior clinical observations suggested that higher hematocrits have been associated with a higher thrombotic risk, which is the reason and the rationale behind phlebotomy and attaining reasonably controlled hematocrit to reduce thrombotic risk. It was data from a site-of-disease study that actually made the connection between lower hematocrit and reductions in the risk of thromboembolic events. I think this is the rationale behind aiming for a hematocrit below 45% and, of course, low-dose aspirin, which is what we have learned from the ECLAP study, in terms of the reduction of cardiovascular events and major thromboses.

In terms of cytoreduction, that’s generally reserved for people who have high-risk disease—although you could argue that, if you have someone who may have low-risk disease but other nontraditional cardiovascular risk and a lot of symptoms, perhaps you would consider cytoreduction again. And here, you’re talking about personalizing and individualizing approaches to therapy in PV patients.

Ruben Mesa, MD: Included in risk assessment and treatment is the importance of the cardiovascular risk factors. Indeed, it’s been shown in the past that if a patient with polycythemia vera primarily sees a cardiologist, their lipids are controlled, their blood pressure’s controlled, and their sugars are controlled, but their blood counts are all over the map. Conversely, if they see a hematologist, we focus on the blood counts, but we largely ignore the cardiovascular factors. The reality is that we really need to address both. Vascular health is a combination of all of these factors coming into play, really at that level of the vascular endothelium. Certainly, there are risk factors that we can control and others that we cannot—age, gender. Clearly, there is no correction for these things. But, we need to be very mindful of the adequate control of lipids, blood pressure, diabetes, and those clear risk factors, as well as have the patient on a smoking cessation program if they’re an active smoker. Smoking with polycythemia vera is really contraindicated.

Jamile M. Shammo, MD: Generally, if I’m employing phlebotomy to optimize somebody’s counts together with aspirin, the phlebotomy will be a lot more frequent in the first few weeks of therapy, until the patient attains a status of iron deficiency. If a patient develops a need for phlebotomy later on in their disease course, then it’s 1 of 2 options. It’s either that their iron parameters suggest they’re no longer iron deficient or that they are, perhaps, developing resistance to cytoreduction, which may bring with it a whole new set of evaluations. You need to worry about dose. Should you be considering alternative treatments?

So, the emergence of phlebotomy need after a period of stability should make the physician who’s treating a given patient concerned, and they should evaluate this patient appropriately for signs of uncontrolled myeloproliferation.

There have been data suggesting that patients who continue to require phlebotomy—in essence, greater than 3 phlebotomies a year—do have an inferior outcome to those who haven’t required any. And so, these are very intriguing data, and I think they merit confirmation in a prospective fashion to truly understand: Do patients who continue to require phlebotomy—and what is the magic number, exactly—truly have a worse prognosis? Because then, it would behoove all of us to identify those patients and treat them appropriately.

Transcript Edited for Clarity