PV: Clinical Use of Hydroxyurea



Ruben Mesa, MD: The initiation of hydroxyurea in patients with polycythemia vera includes its use, I think, in many individuals. And the importance of our new NCCN guidelines is really, in whom do we initiate cytoreductive therapy? So, all patients benefit from a tight control of the hematocrit under 45%. Values above that are clearly associated with an increase in thrombosis from randomized studies. The use of low-dose aspirin, 81 mg or 100 mg, is beneficial. So, that’s all patients with polycythemia vera. Hydroxyurea in individuals who have, at presentation, higher-risk disease features, prior thrombotic event, age over 60—we start it from the get-go. Individuals who have intermediate- or lower-risk disease, we see how things go over time. If they have difficult uncontrolled symptoms, if they have significant leukocytosis, thrombocytosis, cardiovascular risk factors: All of those can be contributors for when we start hydroxyurea.

Over time, as we start it, we look to achieve our treatment goals. The treatment goal is to control the hematocrit, to normalize the white blood cell count and the platelet count, to decrease the size of the spleen to become impalpable, and to control the disease-related symptoms. What I see most commonly is that individuals are treated on hydroxyurea where they have failed “hydroxyurea” because they did not achieve reduction in splenomegaly, improvement in symptoms, or normalization of the white blood cell count or the platelet count.

Uncontrolled polycythemia vera really has 2 main types of branches. One is that there are signs that an individual is resistant to hydroxyurea. So, at either the maximum tolerated dose or 2000 mg a day, they have still an elevation in the white blood cell count or the platelet count or are needing frequent phlebotomies, splenomegaly, or have inadequately controlled symptoms. So, for many, that really is unexpected news in that much of the management of hydroxyurea in the past has been only about controlling the red blood cell count. The importance of both the European LeukemiaNet and NCCN guidelines is that it’s important to control the whole aspect of the disease, not just the red blood cell count. And resistance is really lacking to achieve that.

Intolerance is a reflection of toxicity in achieving that goal. So, is that intolerance due to neutropenia? That’s one set of potential reasons for being intolerant or other cytopenias. Is it intolerance because of cutaneous toxicities? Those are common. That can include skin cancer, can include mouth ulcers, can include leg ulcers, can include GI side effects, and can include fever. So, is an individual resistant or intolerant?

Other ways individuals can “have uncontrolled PV” include the development of a thrombotic event. So, even if you achieve those other things but you have thrombosis, you still didn’t really hit the main goal of our therapy or there’s evidence of progression toward myelofibrosis. So, any of those can be signs really of uncontrolled disease, resistance, or intolerance. The question then becomes, if any of that occurs, then what do we do next? According to our NCCN guidelines and according to the FDA label, the next step is really to use ruxolitinib. Ruxolitinib is approved by the FDA for individuals who have an inadequate response to hydroxyurea therapy. Does it matter whether they were resistant or intolerant? To some degree, it really doesn’t. For some patients, it’s a little bit of a combination of both. Really, if they are inadequately controlled, that is the appropriate next therapy to utilize.

Transcript Edited for Clarity

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