The JAK1/2 inhibitor ruxolitinib can outperform standard therapy in patients with polycythemia vera (PV), results of the RESPONSE trial suggest.
In patients who could not tolerate or were resistant to hydroxyurea, ruxolitinib proved superior to standard therapy for controlling hematocrit levels and reducing spleen volume
“This study indicates that ruxolitinib may represent an important advance for this population of patients with PV,” said Alessandro M. Vannucchi, MD, of the University of Florence in Italy.
Dr Vannucchi and his colleagues reported these findings in NEJM. The trial was funded by Incyte Corporation, the company developing ruxolitinib.
The phase 3 study included 222 patients. They were phlebotomy-dependent, had splenomegaly, and could not tolerate or were resistant to hydroxyurea.
The patients were randomized 1:1 to receive either ruxolitinib (starting dose of 10 mg twice daily) or standard therapy, which was defined as investigator-selected monotherapy or observation only. The ruxolitinib dose was adjusted as needed throughout the study.
The primary endpoint was a composite of hematocrit control and spleen reduction. To meet the endpoint, patients had to experience a 35% or greater reduction in spleen volume from baseline, as assessed by imaging at week 32.
And a patient’s hematocrit was considered under control if he was not eligible for phlebotomy from week 8 through 32 (and had no more than one instance of phlebotomy eligibility between randomization and week 8). Patients who were deemed eligible for phlebotomy had hematocrit that was greater than 45% or had increased 3 or more percentage points from the time they entered the study.
So 21% of patients in the ruxolitinib group met the primary endpoint, achieving both hematocrit control and spleen reduction. But only 1% of patients in the standard-therapy group did the same (P<0.001).
In all, 60% of patients in the ruxolitinib arm achieved hematocrit control, compared to 20% of those receiving standard therapy. And 38% of patients in the ruxolitinib arm had at least a 35% spleen reduction, compared to 1% of patients in the standard-therapy arm.
The rate of complete hematologic remission was significantly higher in the ruxolitinib group than in the standard-therapy group, at 24% and 9%, respectively (P=0.003).
And ruxolitinib-treated patients had a greater reduction in overall symptoms. Forty-nine percent of ruxolitinib-treated patients had at least a 50% reduction in their total symptom score at week 32 (as measured by the MPN-SAF 14-item total symptom score), compared to 5% of patients on standard therapy.
Based on these results, most patients in the standard-therapy arm crossed over to receive ruxolitinib immediately after week 32. So the researchers could only compare rates of adverse events through week 32.
They found that grade 3/4 anemia was more common with ruxolitinib than with standard therapy (2% and 0%, respectively). The same was true of grade 3/4 thrombocytopenia (5% and 4%, respectively) and herpes zoster infections of all grades (6% and 0%, respectively).
However, thromboembolic events were more common with standard therapy. They occurred in 6 patients who received standard therapy and 1 ruxolitinib-treated patient.
The most common non-hematologic adverse events in the ruxolitinib arm were headache (16%), diarrhea (15%), and fatigue (15%), which were mainly grade 1 or 2. The rates of these events in the standard therapy arm were 19%, 7%, and 15%, respectively.
The researchers also noted that nearly 85% of patients randomized to ruxolitinib were still receiving treatment at a median follow-up of 81 weeks.
