Management of Myeloproliferative Neoplasms - Episode 5

Polycythemia Vera: Considerations for Frontline Therapy


Harry P. Erba, MD, PhD: Rami, let’s say that after all of this, you are certain that the patient has PV. It’s not as challenging as we’ve made it. What are going to be the goals of your treatment for that patient?

Rami Komrokji, MD: I think obviously, at this point, the goals have been historically to try to prevent complications, mostly the thrombotic events. We look at the clinical risk factors: if patients are older than the age of 60, if they had prior events; or sometimes other risk factors, like coronary artery disease. The goal has really been mostly preventing thrombotic events. I think the rationale of suggesting the age is that after 60 years old, we see an increase in the risk of arterial events; not that the younger patients are not at risk of thrombosis, but it’s the vascular difference and the age. Arterial events could be more catastrophic, obviously.

The phlebotomies, baby aspirin, and additional cytoreductive therapy if patients had an event or are older than 60 are for that purpose: to decrease that risk. We’ve not looked at the potential of changing the natural history of the disease, so we’ve not had effective therapies or identified patients who may benefit from treatments. If we can identify those patients at higher risk of developing post-PV MF [myelofibrosis], for example, we could target those patients. Those patients have long-term good outcomes in general, and survival, so we don’t think of transplant, even if they have higher-risk PV.

Rarely, we treat patients for symptoms other than just thrombotic events. I’ve had patients who have had severe pain, pruritis, headache, or vasomotor symptoms that would require therapy; not always, but that would be another indication for treating those patients—symptom management and the patient’s related symptoms. Splenomegaly could rarely be an issue in polycythemia vera.

Harry P. Erba, MD, PhD: What are the treatments that are available to our patients for initial therapy, and how do you select those therapies based on patients’ features?

Jamile M. Shammo, MD, FASCP, FACP: I think it’s very important, first of all, to identify the baseline of a patient. Of course, we’re going to do risk stratification. For everybody who has low-risk disease, I think it’s very reasonable to do phlebotomy to a hematocrit below 45%, which has been shown to certainly result in a reduction of thrombotic events. That and low-dose aspirin are the cornerstones of managing patients who have low-risk disease.

For patients who have high-risk disease, when it comes to reducing risk of thrombosis or thrombotic events, I think also there’s another dimension to it, which is perhaps assessing their symptoms at baseline. I think we have Ruben here talk to us about MPN10, which is extremely important prior to starting such therapy.

Obviously, when you need cytoreductive therapy, the choice here is between hydroxyurea and interferon. Most of my patients in practice get started on hydroxyurea. I start with the most common, and we usually start at perhaps 500 mg twice a day, sometimes 3 times a day. Then you monitor the blood counts moving forward. And at some point, you identify a proper dose, and you just simply move forward with that. I reserve interferon for patients who would like to have children, and I obviously couldn’t give Hydrea (hydroxyurea) to this group of people, so interferon is something that I utilize in my practice. I’m happy to say that I’ve actually been fortunate enough to have several women who had children while on this specific therapy. It’s very rewarding. I think that’s basically the ultimate approach to treating PV.

Harry P. Erba, MD, PhD: Jamile, you mentioned the importance of childbearing and conception in your choice of interferon. But another major reason why some guidelines and clinicians pick interferon is for the young patients, because of the concern that hydroxyurea may be leukemogenic. Where do you stand on that?

Jamile M. Shammo, MD, FASCP, FACP: It’s a very interesting question, because obviously, you have a disease that has the propensity to develop into acute leukemia—perhaps in this case, PV, myelofibrosis, and then AML. How do you actually dissect the role of Hydrea in adding to that leukemogenic potential? Unfortunately, there are no prospective longitudinal long-term data that would tell you whether or not this is the case. But I think at least in a retrospective analysis and looking at all the data on hydroxyurea patients, this doesn’t seem to be corroborated. But can I tell you 100% that I don’t think it can add to the leukemic potential? I don’t think I can.

Rami Komrokji, MD: I think the evidence was not conclusive or that there was no statistical significance. But the other point I argue for sometimes using interferon is that the pegylated forms of interferon in younger patients could potentially be a therapy that alters the natural history of the disease, whereas with Hydrea or hydroxyurea, you don’t have evidence for that. I think that’s the other point. I worry about putting somebody who is 20 years old on Hydrea for 40 years, although the evidence is not conclusive.

Jamile M. Shammo, MD, FASCP, FACP: Yes.

Harry P. Erba, MD, PhD: Well, we’re going to come back to that point about interferon changing the natural history and look at some clinical trial data.

Srdan Verstovsek, MD, PhD: But with Hydrea, we talk about a gray area of acute myeloid leukemia. The obvious area we forget is squamous cell carcinoma.

Rami Komrokji, MD: And solid tumors.

Srdan Verstovsek, MD, PhD: That’s just proven in a way. I live in Texas now, and I see so many patients with the squamous cell carcinoma, maybe from the sun. But in areas of the world where that’s not the case, they have published and verified that hydroxyurea actually does increase the risk of squamous cell carcinoma. People don’t know that.

Transcript Edited for Clarity