Polycythemia Vera: Switching Therapy

Harry P. Erba, MD, PhD: One of the things I’ve noticed in the NCCN Guidelines that I’ve had questions about concerns a patient on a cytoreductive therapy, whether it’s interferon or hydroxyurea. And let’s assume that they’re having adequate control of their blood counts and tolerating therapy. Having another thrombotic event requires a switch to therapy, and I’m wondering: Is that necessary? How do you make that choice about what you switch to? Ruben?

Ruben A. Mesa, MD, FACP: It’s an excellent question. It depends a bit on the circumstance. Is it a new thrombotic event in a different vascular distribution? Is it extension of a prior clot? If it was a DVT, sometimes it’s difficult to know if it is an extension of a prior clot or a new clot in a different area. Were the counts controlled at the time that they had the second event?

I try to see if it is a failure of the therapy or if it is a failure of some other thing. Was it a true event? Without question, in terms of second-line therapy, we now have an FDA-approved second-line therapy of ruxolitinib for individuals with PV [polycythemia vera] who also can be indicated clearly in that second-line setting, and it is particularly helpful if they have splenomegaly symptoms or more difficult disease-associated features.

In the studies, there is a suggestion of further protection against thrombotic events. Those studies were not necessarily powered for thrombosis as a primary end point, but there is some thought that it decreases inflammation and other aspects that may be improved by the JAK1/2 inhibition and might be beneficial in terms of thrombosis prophylaxis.

Harry P. Erba, MD, PhD: Jamile, what would cause you to switch from whatever cytoreductive therapy you’re on to another—ruxolitinib or interferon if you’re on hydroxyurea—other than thrombotic events?

Jamile M. Shammo, MD, FASCP, FACP: It has to do with the tolerability of the cytoreductive therapy and the results I’m looking for. Some patients are unable to tolerate hydroxyurea. I’ve had a patient who had significant allergic reaction to the drug, so I had no way to do it but to switch to ruxolitinib in this instance.

I would switch if somebody is developing unexpected or untoward [adverse] effects from the dose of Hydrea [hydroxyurea] that is required to control their blood counts or constitutional symptoms or if they start to develop splenomegaly despite being on Hydrea [hydroxyurea] or other forms of cytoreduction. There are a multitude of reasons, and in patients who have PV, every patient has to be dealt with individually. We have to ask ourselves: “Have we optimized the doses? Have we talked about compliance? Can we up the dose before we make the switch?”

It is a commitment on both the patient and my part to say, “Now we’re ready for part b.” All the issues that have been mentioned could lead to a shift in therapy. The issue is that you need to continue to monitor the treatment and response to treatment, and that is something that may not have been optimized because we think PV is a chronic disease. When patients have very little symptoms, some say “Take your Hydrea, see you later.”

It’s very important to monitor response to treatment, look at the blood counts and constitutional symptoms, and talk with the patient about whether we are optimizing this to the fullest. If not, then switch.