Ruben Mesa, MD: The RESPONSE study was the pivotal phase III study for the approval of ruxolitinib as a second-line therapy for patients with polycythemia vera, and it was approved on the basis of efficacy as measured by helping individuals become phlebotomy independent, have reduction in difficult splenomegaly, and have improvement in symptoms. These were individuals who had difficult PV. They had failed hydroxyurea; they had higher-risk disease. It helped to improve all those difficulties. Overall, it was found to be a drug that was very safe. It can lower the counts—that’s one of its potential side effects. In patients with myelofibrosis, that sometimes can be a limiter. But in polycythemia vera, that really aligns well with our therapeutic goals of trying to control the red blood cell count, the white blood cell count, and the platelet count.
It’s a therapy in terms of the toxicities that I’m mindful of. It can increase the risk of herpes shingles. That’s probably in about 5% or 6%. It’s far from universal but is not irrelevant. So, I am mindful of it. I do counsel patients about that, and certainly if they start to develop symptoms of shingles, we rapidly do give them a prescription for antiviral therapy. It’s not a common occurrence but is important to be mindful of. These individuals have a higher rate of nonmelanoma skin cancers. Now, in my mind, it still is difficult to know whether that is a ruxolitinib side effect or not. It is in the label. The confounders are that MPN patients, as a group of individuals, have a higher rate of nonmelanoma skin cancers. They, by definition, all had failed hydroxyurea, and that clearly increases a rate of nonmelanoma skin cancers. So, those are additional things that I’m mindful of.
Now, my clinical experience has been very favorable with ruxolitinib in PV, and it very much matches that of the RESPONSE study. And having been an investigator in the RESPONSE study, I can say that it’s very consistent with my practice now. Patients have improvements in splenomegaly, if present. I haven’t found that they need to have splenomegaly to benefit. The RESPONSE-2 study similarly showed that individuals don’t have to have splenomegaly to benefit. Individuals, if they have symptoms, really can have significant improvement. Particularly difficult symptoms, such as pruritus, really tend to respond to very few things other than ruxolitinib, as well as clearly controlling the counts and likely decreasing the rate of thrombotic events. So, the clinical experience, I’d say, has been favorable and very consistent with the published studies.
The ruxolitinib side effects in polycythemia vera, I find, tend to be pretty modest. There can be cytopenias, but they rarely are a limiter or problematic. For individuals who have developed shingles—of which I’ve had a couple, but that’s out of a large group of patients I’ve treated—we have started antiviral therapy in a rapid time frame to really limit that course. In the past, we did not have a vaccine that we felt was safe to use in these individuals because it was a live vaccine. There now is an inactivated vaccine for herpes shingles that has become available. There are zero data in patients with PV one way or the other, but I think for individuals on the therapy, I have been recommending that therapy to them even in the full absence of data based on the safety of that vaccine as well as the potential benefit that it may have for those individuals.
Transcript Edited for Clarity