Response to Ruxolitinib Therapy for Polycythemia Vera

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Srdan Verstovsek, MD, PhD: Ruxolitinib was approved as a second-line therapy after hydroxyurea in patients with polycythemia vera and a high risk for thrombosis. The RESPONSE study showed that it was significantly superior to best available therapy in controlling the red blood cells, white cells, platelets, symptoms, and spleen. Practical implications of this are that, with the control of those numbers in particular, we decrease the risk of thrombosis. All of those were not official endpoints for the study. We know from the longer follow-up of patients on the 2 arms that, indeed, on a safety analysis, there was a significant difference in the number of thromboembolic events. Only a few on the ruxolitinib arm, compared to quite a few on the best available therapy arm, indicated that control of the blood cell count possibly led to a decrease in thromboembolic events. Additionally, quality of life for the patient is quite important these days. We are not only talking about the blood cell count and decreasing the risk of thromboembolic events. Quality of life with ruxolitinib gets improved quite rapidly, within 1 month, which was seen in the majority of patients in the RESPONSE trial who were given ruxolitinib.

Assessing the efficacy of any therapy that we provide to patients with polycythemia vera and a high risk of thrombosis has to include control of the general symptoms that are related to PV. We are talking about the person these days, not only about hematocrit control, or perhaps control of white cells or platelets. Many patients, even with good control of the red blood cells on hydroxyurea as a first choice, can have uncontrolled symptoms related to polycythemia vera that ranges from itching, to burning in the feet, to blurred vision, to headaches, to hypersensitivity of the skin. These are the symptoms that cannot be overlooked when we talk to patients with polycythemia vera. It is mandatory to interact with the person who has PV and ask about their quality of life. In this setting, ruxolitinib can help, because by its the mechanism of action—controlling the JAK/STAT pathway, which is important for the inflammation that causes these symptoms—it is very valuable to help patients who have poor quality of life, even if they have good control of their blood cell count.

Jamile M. Shammo, MD: A patient who’s responding appropriately to Hydrea [hydroxyurea]—tolerating the medication well, responding well in terms of normalizing blood parameters, keeping the hematocrit below 45%, and having a reasonable quality of life—should stay on this therapy. But if you have a patient who is unable to tolerate this medication and has inappropriate parameters—symptoms that are not well-controlled by the drug—then I think a discussion about options of therapy is very reasonable.

Ruben Mesa, MD: Ruxolitinib has now been used in patients for 10 years. Dr. Verstovsek and I put the first patients on the initial studies with myelofibrosis back in 2007. Some of those patients remain on the therapy without any indication that long-term use leads to any unexpected long-term side effects. Our experience with polycythemia vera is more recent, in that the drug was developed in myelofibrosis first, but that experience still extends back to 2011, 2012, and we have patients who have been on it for that full stretch of time. So, all indications, at the current time, are that it is a therapy that is well-tolerated for the extended suppression of the disease, and that we do not have an indication of a long-term toxicity we need to be mindful of.

Transcript Edited for Clarity