Management of Myeloproliferative Neoplasms: A Focus on Polycythemia Vera and Myelofibrosis - Episode 7

Cytoreductive Therapy in Polycythemia Vera


Harry P. Erba, MD, PhD: We kind of agreed on some of the major reasons for using cytoreductive therapy, and some of the controversies. If we’ve started cytoreductive therapy, when do we determine that we’re just not controlling the diseases as adequately as we want. Rami?

Rami Komrokji, MD: Ruben covered, elegantly, some of those elements. I think at the beginning, the key is really monitoring those patients frequently. I see sometimes that patients get started on treatment or phlebotomy, and their counts are checked once every 2 or 3 months. At the beginning that’s inadequate. Those patients need to be monitored often at the beginning, maybe the blood counts every other week or bring them in every month until we get to that steady state or maintenance state. I think that’s key.

Obviously, what we look at are the blood counts and how well they’re controlled. The symptoms for the patients are also things we look at. Obviously, once we start the cytoreductive therapy, what comes into the equation is also the toxicity or adverse effects of those medications and how well the patient is tolerating those treatments, and based on that we decide. Usually, for example, with Hydrea, I think there are certain doses which, once you get to and you’re not able to control the disease, that probably would be a signal to consider changing treatment. When you get into the 3 g range of Hydrea to try to control patients with P vera [polycythemia vera], the likelihood of running into adverse effects is going to be much higher.

If the patients are developing cytopenias with the treatment, that would be a sign to shift the treatment, and again, the symptom control. There are patients with P vera, maybe a smaller subset, who will have constitutional symptoms or itching that are not controlled with a first-line cytoreductive therapy, that sometimes will need a second-line consideration because of that.

Harry P. Erba, MD, PhD: OK. We’ve been talking around the CYTO-PV [Cytoreductive Therapy in Polycythemia Vera] study and how it directs our management, and we have this cutoff. I’ll ask Jamile a slight twist on that question. How strict do we have to be? If the patient is coming in for monthly blood counts, is consistently requiring a phlebotomy, and you know that they’re spending some of their time above 45%, is that a reason for considering cytoreductive therapy?

Jamile M. Shammo, MD, FASCP, FACP: There were data, albeit retrospective, looking at the frequency of phlebotomy and outcome. Presumably, if your patient requires more than 3 phlebotomies a year, then that correlates with a worse outcome. This is from Alberto Alvarez-Larrán MD. I think the 1 thing that we could control safely is the hematocrit. The CYTO-PV study demonstrated beyond doubt that keeping patients below 45% is associated with a 4-fold decrease in thrombotic events. Fine, we’re not be able to control disease progression, but I can certainly control the hematocrit.

Granted, when you start to phlebotomize someone early on in the disease course, you probably have to do the CBCs [complete blood counts] a whole lot more frequently, perhaps once a week. I have people with hematocrits of 68%. Those people may need it twice a week until I am certain that they are optimized. Afterward, you kind of stretch the durations between CBC monitoring. To your point, we have to be very cognizant of the fact that if someone is tethering around 45%, perhaps you want to maybe go for a lower cutoff so that you’re not having instances whereby they are above 45%. Those are all the things that you have to think about.

Harry P. Erba, MD, PhD: Rami, you brought up a very important point about going to 3 g of hydroxyurea a day to control the disease. The ELN [European LeukemiaNet] criteria say a patient should be treated with at least 2 g a day for 3 months before you decide that somebody is not responding or having all the benefits of cytoreductive therapy. You have to be monitoring and titrating the dose, but at some point you will decide that you cannot push the dose anymore because of intolerance or you’re just not getting response.

Transcript Edited for Clarity