Data from the new study support ruxolitinib as an effective long-term treatment option for patients with polycythemia vera.
"Our data support ruxolitinib as an effective long-term treatment option for patients with [polycythemia vera (PV)] who have had an inadequate response to or who are unable to tolerate conventional hydroxyurea treatment," Jean-Dr. Jacques Kiladjian, professor of clinical pharmacology at Paris Diderot University in Paris, France, said.
Dr. Kiladjian and colleagues conducted a pre-planned analysis of the global, phase 3 RESPONSE study in order to determine the long-term efficacy and safety of ruxolitinib after all patients completed the week 80 visit or withdrew from the study. Ruxolitinib is a Janus kinase 1 and 2 inhibitor.
In the study, 222 patients who were intolerant or resistant to hydroxyurea were randomized to open-label ruxolitinib 10 mg BID or best available therapy (BAT). Best available therapy included hydroxyurea (at a dose that did not cause unacceptable side effects), interferon or pegylated interferon, pipobroman, anagrelide, immunomodulators such as lenalidomide or thalidomide, or no medication.
Patients randomized to BAT could cross over to ruxolitinib from week 32.
Hydroxyurea is the most commonly used first-line cytoreductive agent, Dr. Kiladjian pointed out. Although many PV patients have an adequate response to hydroxyurea, about 25% of patients have unacceptable side effects or an inadequate response, and alternative treatment options are needed for these patients.
He also noted that some patients have a high symptom burden that may include itching, fatigue and night sweats, which respond poorly to standard therapies.
At the data cut-off for the 80-week analysis, 82.7% of patients randomized to ruxolitinib were still receiving treatment (with a median exposure of 111 weeks) compared to no patient in the BAT arm.
The composite primary endpoint of both hematocrit control without phlebotomy through week 32 and a ≥ 35% reduction from baseline in spleen volume by imaging at week 32 occurred in a significantly higher percent of patients in the ruxolitinib group than in the BAT group (20.9% vs 0.9%).
Overall, 60.0% of ruxolitinib patients versus 19.6% of BAT patients achieved hematocrit control without phlebotomy through week 32; patients achieving hematocrit control in the ruxolitinib arm had an 89% probability of maintaining this response for 80 weeks from the time of their initial response. Of patients on ruxolitinib at week 32, 89.8% did not have a phlebotomy between weeks 32 and 80.
At week 32, 38.2% versus 0.9% of patients in the ruxolitinib versus BAT arm achieved a ≥35% reduction in spleen volume; all ruxolitinib patients maintained their response.
At week 32, complete hematologic remission was achieved in 23.6% of ruxolitinib patients and 8.9% of BAT patients, with ruxolitinib responders having a 69% probability of maintaining complete hematologic remission for 80 weeks.
A separate analysis at 18 months showed that ruxolitinib treatment also resulted in sustained control of white blood cell and platelet levels, with the largest decreases in patients with the highest baseline levels.
Ruxolitinib generally remained well tolerated. Most adverse events were grade 1 or 2, and there were few grade 3 or 4 cytopenias. As reported in a prior analysis, the rate of herpes zoster was higher in the ruxolitinib arm.
The RESPONSE study was conducted at 90 sites worldwide.