Management of Myeloproliferative Neoplasms: A Focus on Polycythemia Vera and Myelofibrosis - Episode 9

RESPONSE-2 Trial: Ruxolitinib for PV


Harry P. Erba, MD, PhD: In the RESPONSE trial, those patients required phlebotomies and had to have splenomegaly to be eligible. Some have criticized the study by saying, “Well, that’s not really a goal of my therapy in most PV [polycythemia vera] patients.” However, there are data looking at patients who don’t have splenomegaly in the RESPONSE-2. Rami?

Rami Komrokji, MD: The RESPONSE-2 was a similar design to the RESPONSE-1, but in terms of the eligibility, there was no requirement for spleen enlargement or splenomegaly. In RESPONSE-1, it was a composite endpoint looking at spleen response, as well as adequate control. In RESPONSE-2, the study had patients who were intolerant or resistant to Hydrea. They were randomized between best available therapy or ruxolitinib, and the primary endpoint was looking at adequate control of the blood counts. The study was presented originally and updated later showing durable responses in the range of 40%-plus with adequate hematocrit control. Again, symptom control occurred in more than half of those patients. The value of the ruxolitinib in patients with P vera [polycythemia vera] is not just for the spleen reduction. I think it’s for the count control.

There is subset of 20% or 25% of the patients who will achieve a complete hematological response where they normalize their other counts. Splenomegaly does happen. We observe it, as you mentioned earlier. Most often, it’s not relevant symptomatically for the patients early in the disease. It may be later on an indication for treatment. Other symptoms, as mentioned, for example, itching and constitutional symptoms are probably more prevalent. The RESPONSE-2 nicely shows that the goal of the treatment was not just control of the spleen, but actually providing count control and symptom improvement, which is very important for those patients.

Harry P. Erba, MD, PhD: Right. I know we’ve gone through the CYTO-PV study showing the importance of hematocrit control and the data for white count control. Are there actual data with ruxolitinib that we’re doing what we talked about at the beginning, which is decrease the risk of thrombotic events?

Rami Komrokji, MD: That’s a very interesting point you raise. I don’t think it had been looked at as a primary endpoint in those studies, but if I recall correctly, in RESPONSE-1, it was reported almost in the adverse effects. The thrombotic events were a little bit less frequent with ruxolitinib than with Hydrea. Ruben may correct me if I’m wrong.

Ruben A. Mesa, MD, FACP: Sure. It was not one of the primary endpoints, and I think it’s a reflection that the rate of events would have not been practical in terms of the study. In terms of the trend, it’s very significant. There clearly are many fewer events in the ruxolitinib-treated patients versus those who have received best alternative therapy, and there are a variety of reasons to really believe that data. First is the better control in the counts, but second, the decrease in the inflammatory milieu, which likely is contributory to a prothrombotic state, is really improved. I think there’s definitely that expectation that you’re helping to decease that rate of events.

Rami Komrokji, MD: Also, in terms of adverse effects, when we mention the skin malignancies, I think that’s an important point to keep in mind for all patients with MPN [myeloproliferative neoplasms] because I think they are at a higher rate. Even in those studies, when you look at the ruxolitinib versus the Hydrea, I think the rates were higher with Hydrea still than with ruxolitinib. It’s an important point to keep in mind for all our patients, that they need those annual checkups. I don’t think the rate is higher with ruxolitinib than with Hydrea.

Harry P. Erba, MD, PhD: Yes. If you put both RESPONSE-1 and RESPONSE-2 together, there were numerically more thrombotic events with best available therapy. Of course, the study wasn’t powered and it’s a very short follow-up. It was 32 weeks at the time of the primary endpoint, and clearly, this is a chronic illness. One of the nice things that we’ve seen from the long-term follow-up of RESPONSE-2 is that patients are staying on therapy, suggesting that their disease is controlled, actually. They did show that.

Transcript Edited for Clarity