Mary Frances McMullin, MD, FRCP, FRCPath: When we treat any disease, we would like to think our goal of therapy is to cure the disease, and in my book, that would be eliminating the acquired malignant clone. That is not what we are doing, or we’re not anywhere near that yet. Our main goal of therapy is to try to prevent thromboembolic events because that was what killed these people. The original study showed that without therapy, 50% of people were dead within 18 months. That’s with no treatment, no venesection, and that was mostly because of thromboembolic events. Our first goal of therapy, as we talk of therapies, will be to prevent thromboembolic events. The other things we would like to do but perhaps we don’t have the tools to do, would be to prevent progression either to myelofibrosis or acute leukemia. Actually, our main goal of therapy, practically, is the prevention of thromboembolic events.

Harry P. Erba, MD, PhD: Ruben is our expert on symptoms, and also symptom control for the disease. How do you manage PV [polycythemia vera] when you first make the diagnosis? What is your management? What agents do you have?

Ruben A. Mesa, MD, FACP: Well, first I think it’s important for physicians to really view the management of PV as a chronic disease. As I speak with patients and try to have them wrap their head around having this chronic neoplasm, they’ll look on the Web and they’ll be thinking of other cancers—breast cancer, colon cancer, etcetera—that have intensive cyclical therapy for a period of time. Here we’re clearly talking about a long-term management to try to make the disease as neutral in their lives as possible in terms of risk of thrombosis, controlling symptoms, and avoiding progression.

In terms of our current US-based guidelines, the NCCN [National Comprehensive Cancer Network] guidelines, to which many of us were contributors, the first step, which is clear, and internationally there’s no dispute about this, is control of the hematocrit. The single most important part that all PV patients need to have is hematocrit controlled under 45%. Now, there may be modifications to that. There may be some patients who do a little better a little lower than that, so you have to have good common clinical sense in terms of their phenotype or symptoms. There’s discussion regarding whether that level should be a little lower in women—although there’s probably not rock-solid evidence around a number for that, but clearly under 45%—whether that is through phlebotomy, or medication, or some combination therein.

Second is a low-dose aspirin. Although that seems very intuitive, even when I was training, aspirin was felt to be contraindicated. There had been early studies in the ’60s in which high doses of aspirin were used, and there was higher risk of GI [gastrointestinal] bleeding. For a long time, it was felt to be contraindicated, but likely was an issue of dose. Now, low-dose aspirin is supported through randomized studies, from European studies where they use 100 mg versus the more common 81 mg in the United States, as a standard. All PV patients should have hematocrit control and low-dose aspirin.

The trickier decision making is regarding the initiation of cytotoxic therapy, which at the current time, includes hydroxyurea and in frequent guidelines, potentially the use of interferon. In terms of cytoreductive therapy, who benefits from cytoreductive therapy? The guidelines vary a little bit on this. The group for which it’s by far the clearest are people who have had prior thrombotic events or vascular events. That is, by far, the clearest. Regardless of age and other things, if you’ve already had 1, you’re clearly at greater risk of having another.

Second is the issue of increasing age in terms of benefitting from that. Is that 60? Is that 65? Is that a physiologic 60? I think that there’s more dispute. Without question, aging is a factor. Our vessels age, our risk factors for developing events age, and sometimes, the first event that you have is a catastrophic one. We take those very seriously. Then, there is a group of potential indications for cytoreduction that are a bit grayer, but are important to consider, including adequate control of symptoms and intolerance of phlebotomy alone as a management strategy. Some patients just don’t tolerate cyclical phlebotomy very well and develop severe symptoms from the iron deficiency of chronic phlebotomy.

There’s a range of things in there. There’s clearly variable risk of cardiovascular health that contributes to it. The 58-year-old who has hypercholesterolemia, hypertension, and 2 stents is in a very different position than the person who has pristine cardiovascular health in their 50s or things of that nature. That’s another important component, as well. If I see an unmet need in terms of the patients I see referred, it’s frequently around that decision point of going from phlebotomy and aspirin to the initiation of therapy, and frequently people who should have been started on initial therapy are not.

Transcript Edited for Clarity