Polycythemia Vera: Ruxolitinib Use and Goals of Therapy


A brief discussion on the role of ruxolitinib in the management of polycythemia vera, followed by a review of goals of therapy in this setting.


Ruben Mesa, MD: Ruxolitinib is an oral inhibitor of JAK2, first approved in myelofibrosis but now approved in polycythemia vera. It was tested in a trial that I was involved with, the RESPONSE study, which was a randomized study compared the best alternative therapy for individuals that had P-vera [polycythemia vera], had failed hydroxyurea, had splenomegaly and needed alternative therapy. Ruxolitinib was found to be vastly superior to best alternative therapy for control of the hematocrit, improvement in symptoms, and over time, suggestion of improvement in risk of vascular events and other secondary benefits. The RESPONSE-2 study was really a parallel study, but without the necessary eligibility criteria of the presence of splenomegaly. The results really were just as favorable: improvements in control of the hematocrit, improvement in symptoms in these individuals that needed control. Ruxolitinib is an important therapy in P-vera, in the current NCCN [National Comprehensive Cancer Network] guidelines, it’s a second-line therapy, particularly if individuals have splenomegaly symptoms or other difficulties.

Stephen Oh, MD, PhD: As far as goals of therapy for patients with PV [polycythemia vera], there are a variety of important factors to keep in mind. The first is that we know these patients are at risk for thrombosis, and so we want to mitigate that risk. And one specific goal in that regard is to maintain the hematocrit below 45. That’s been substantiated, in particular, by the CYTO-PV [Cytoreductive therapy in PV] study, which was conducted in Italy, establishing that a more tighter control of hematocrit below 45, as opposed to a more liberal hematocrit target, did result in a superior outcome as it related to thrombosis and cardiovascular complications. Thus, whichever treatment modality is used, in general, that goal is important, to keep the hematocrit below 45. Again, that relates in part to reducing risk of thrombosis, but there are other goals of therapy as well, including for those patients that have symptoms related to PV.

And if that is the case, for instance, many patients with polycythemia vera have problematic itching, classically, aquagenic pruritus, so that worsens after taking a hot shower. Therapies may be chosen, or the goal may be to direct therapies to reduce those bothersome symptoms. And thirdly, a goal of treatment, of course, would be to ameliorate the disease overall and prevent long-term complications, including transformation to myelofibrosis or, in some cases over time, potentially, risk of transformation to leukemia. Thus, in that regard, a goal of treatment would be to alter the long-term trajectory of the disease, put the disease into remission. That would not necessarily just be indicated by control of the blood counts, but for instance, inducing a molecular response or remission, reducing the JAK2 immune allele burden, and so on and so forth. Hence, therapies may be evaluated or chosen with these different goals in mind.

Transcript edited for clarity.

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