Harry P. Erba, MD, PhD: Ruben, I’m going to turn to you. For our viewers, Ruben chairs the NCCN MPN Guidelines committee. I would like you to comment on what the NCCN recommends for initiation of cytoreductive therapy. When do you consider that in terms of that choice? Then, follow-up on that with the comment of whether it is hydroxyurea or interferon: how do you use those?

Ruben A. Mesa, MD, FACP: First, to give proper credit, I did initiate that group as the initial panel, but it is now chaired by our friend and colleague Aaron Gerds. I am very familiar with the NCCN Guidelines. They’re a key piece. Srdan and I were on that initial wave helping to set these up. They were positive in that they brought some evidence-based standards to our US–based treatment.

Cytoreductive need for high-risk patients in PV is aimed at both decreasing that difficult risk of thrombosis and bleeding as well as trying to improve the disease burden with symptoms. 2 options are listed as initial therapy; we’re building on that base and assuming that people have already been on phlebotomy and aspirin. That’s a base: control of hematocrit and aspirin. The cytoreduction, then to try to achieve a European leukemia net response: phlebotomy independence, control of the white blood cell count, control of the platelet count, and resolution of splenomegaly if they’re in control of symptoms.

With that, either hydroxyurea or long-acting interferons: both are thought to be clinician’s choice, between them and the patients. There are increasing data; there are randomized data from earlier studies showing that hydroxyurea is superior to phlebotomy alone. It’s an older drug, but people are frequently comfortable using it.

Deficiencies can be difficulties with cytopenias, mouth ulcers, cutaneous malignancies, and sometimes other associated adverse effects. For interferons, there is an update coming up at this year’s EHA. We saw it in the late-breaking abstracts regarding the pegylated interferon given every 2 weeks. In the US most commonly, the pegylated interferon alpha 2A has been the available construct.

When trying to achieve a good control of the counts, on the downsides with interferon, it can cause mood disorders, or rarely, autoimmune problems such as hypothyroidism, or flu-like symptoms. Both have their pluses and minuses, with interferon being the preferred choice in women of childbearing age or individuals who are pregnant.

Transcript Edited for Clarity