A comprehensive review of the treatment armamentarium for polycythemia vera, as well as strategies to monitor patients on therapy in this setting.
Prithviraj Bose, MD: This patient started with phlebotomy and aspirin, and then hydroxyurea was added when they had symptoms and they continued to need phlebotomy. In my practice, for a high-risk patient, I start with hydroxyurea. The hematocrit is always less than 45% based on the CYTO-PV trial. When I see them, if the hematocrit is higher than that, I’d probably order a phlebotomy along with prescribing hydroxyurea, but I typically don’t rely on just phlebotomy for a high-risk patient. I usually go straight with hydroxyurea.
The NCCN [National Comprehensive Cancer Network] Guidelines for MPNs [myeloproliferative neoplasms] were just updated in April 2022. There’s a new player on the market ropeginterferon alpha-2b was approved by the FDA in November 2021. This drug has a broad label for polycythemia vera [PV], and it’s mainly being studied in a frontline setting or a setting with minimal prior hydroxyurea treatment. I regard it more as a frontline drug than as a second-line drug. That’s a new treatment option as well to consider in today’s day and age.
The goal of treatment in PV, first and foremost, is to maintain that hematocrit under 45%, so that we reduce the risk of clots. Thrombosis is the main end point that we’re trying to avoid, and the treatments are tailored to reduce that risk. There can be rare bleeding as well, usually when the platelet count is extremely high. But that’s more of an issue in ET [essential thrombocythemia] than in PV. We’re trying to reduce the thrombotic risk for the patient. One of the primary means of achieving that is by getting the hematocrit under 45%. There are also some good data that suggest that controlling the white blood cell count below 11 per mm3 is important to that end.
With this patient we saw that the hydroxyurea dose had to be increased quite a bit. They started at 1000 mg and then went all the way up to 2000 mg. Some of it was symptom driven. That’s certainly reasonable because hydroxyurea can have some symptom benefit, although I don’t regard it as a great drug for symptoms. In my view, it’s more effective in controlling blood counts and preventing the risk of clotting, but sometimes that’s worth a try. Medications such as ruxolitinib [Jakafi], which we’ll come to later, are probably a lot better for symptom control.
Of course, patients with PV need to be assessed regularly. I typically see them every 3 months. However, in the beginning it can be a lot more frequent. You may need to see somebody every week or every 2 weeks while you’re getting that hematocrit stabilized, especially if it’s a low-risk patient in whom you’re not using a drug and just relying on phlebotomy. For high-risk patients, I typically start with a cytoreductive drug right off the bat. They may need to be seen pretty frequently initially.
As far as response goes, there are ELN [European LeukemiaNet] criteria, but these are more applicable for clinical trials. Frankly, in everyday patient management we’re using our clinical impressions of how well their symptoms are controlled and of course blood counts, with the goal being hematocrit under 45% at all times and, to the extent possible, white blood cell count less than 11 per mm3. The platelet count is less important to control because it doesn’t correlate with clotting risk for the most part. Some studies suggest that it might, but most studies don’t show a correlation between the platelet count and thrombotic risk. On the other hand, if the platelet count is extremely high—more than 1.5 million per mm3, there’s a bleeding risk. However, that’s much more of an issue in ET than in PV.
Transcript edited for clarity.