Ruxolitinib in PV: The RESPONSE-2 Trial

Jamile Shammo, MD, FASCP, FACP: Interestingly, you realize that these data were obtained for patients with PV [polycythemia vera] along with splenomegaly, but there are also data for patients who have PV who are dependent on phlebotomy without splenomegaly. This is where the RESPONSE-2 trial comes in. These data come from Dr. Francesco Passamonti and colleagues who conducted a study very similar in its design to the RESPONSE trial. This trial is called RESPONSE-2, and it’s a randomized, open label phase 3B study that was conducted in patients who met similar criteria in that they were Hydrea [hydroxyurea]-resistant and intolerant. They were phlebotomy-dependent, but they didn’t have splenomegaly. That was the only difference. They were randomized 1:1 to ruxolitinib at 10 mg twice a day to best available therapy.

When they were followed, the primary end point was also freedom from phlebotomy in this case. Because they didn’t have a spleen, you couldn’t actually assess reduction in spleen volume. They were followed for symptom improvement. This analysis was similar to the RESPONSE trial in that 60% of the patients similar were able to achieve freedom from phlebotomy, and there were fewer people who developed hematological toxicity. When you think about this, patients who have PV start out with much higher hematologic parameters like hemoglobin and hematocrit levels to begin with. The likelihood of running into trouble with cytopenias is much lower with a drug that may have myelosuppressive properties. In the initial analysis, RESPONSE-2 met its primary end point. Therefore, this could be considered a standard of care for this patient population.

This past year, in 2020, the same group reported on the final analysis on the 5-year data for the RESPONSE-2 trial. In a very similar fashion to the RESPONSE trial, they also reported on durable responses for patients who became free from phlebotomy and those who entered complete remission with lower thrombotic events and lower chances of attaining other adverse events. There was also a slightly increased risk for herpes zoster infection of about 4% in patients who were randomized to the ruxolitinib arm, so that’s something about which we also need to be cognizant.

To make sure that the patient I’m starting on ruxolitinib is reaping the benefit of this effective treatment, I tend to monitor them very closely in the first 2 months of therapy. I will also make sure that their kidney function, liver function test, and their other hematologic parameters are monitored very closely, and I will adjust the dosing accordingly. That’s pretty much what I do. I monitor the dose very closely, monitor the kidney parameters, and make sure that we follow the packet insert recommendations for those holding any modification.

Like I already said, patients who have polycythemia vera have higher hematological parameters to begin with, though that is no excuse. We have to monitor them closely, but if you look at the safety, the grade 3 and 4 hematologic toxicity with ruxolitinib at the starting dose of 10 mg BID [twice daily], those numbers are rather small. Again, we need to monitor very closely, and for patients who have a history of herpes zoster infections, I might put them on prophylactic doses with acyclovir BID, and for those who end up developing it while on treatment, I will also treat them and then put them on prophylactic doses of acyclovir while on ruxolitinib.

TRANSCRIPT EDITED FOR CLARITY