Ruxolitinib Better Than Standard Therapy in Polycythemia Vera Patients With Inadequate Response to or Intolerance of Hydroxyurea


Key Points

  • The primary endpoint was achieved in 21% vs 1% of patients.
  • Hematocrit control was achieved in 60% vs 20%, and ≥ 35% reduction in spleen volume was achieved in 38% vs 1%.

In a phase III trial reported in The New England Journal of Medicine, Vannucchi et al found that the JAK1/JAK2 inhibitor ruxolitinib (Jakafi) produced significantly better hematocrit control and reduction in spleen volume than standard treatment in patients with polycythemia vera with inadequate response to or intolerance of hydroxyurea. The trial supported the recent approval of ruxolitinib in this setting.

Study Details

In the open-label trial, 222 phlebotomy-dependent patients with splenomegaly and hematocrit control between 40% and 45% were randomly assigned between November 2010 and February 2013 to ruxolitinib at a starting dose of 10 mg twice daily (n = 110) or standard therapy (n = 112). The ruxolitinib dose could be increased to 25 mg twice daily. Standard therapy included hydroxyurea (60%), interferon (12%), anagrelide (7%), pipobroman (2%), lenalidomide (Revlimid)/thalidomide (Thalomid) (5%), and observation (15%). The combined primary endpoint was hematocrit control defined as absence of phlebotomy eligibility beginning at week 8 and maintained thereafter and spleen volume reduction of ≥ 35% at week 32.

For the ruxolitinib and standard therapy groups, median age was 62 and 60 years, 60% and 71% were male, 46% of both had inadequate response to prior hydroxyurea, 35% and 29% had prior thromboembolic events, and 95% and 96% were JAK2 V617F–mutant positive.


The primary endpoint was achieved in 21% of the ruxolitinib group vs 1% of the standard therapy group (P < .001). Hematocrit control was achieved in 60% vs 20%, and ≥ 35% reduction spleen volume was achieved in 38% vs 1%. Complete hematologic remission occurred in 24% vs 9% (P = .003), and 49% vs 5% had ≥ 50% reduction in total symptom score at week 32.

Grade 3 or 4 anemia occurred in 2% of the ruxolitinib group vs 0% of the standard therapy group; grade 3 or 4 thrombocytopenia occurred in 5% vs 4%. Herpes zoster infection (all grade 1 or 2) occurred in 6% vs 0%. Thromboembolic events occurred in one patient (1%) vs six patients (5%).

The investigators concluded: “In patients who had an inadequate response to or had unacceptable side effects from hydroxyurea, ruxolitinib was superior to standard therapy in controlling the hematocrit, reducing the spleen volume, and improving symptoms associated with polycythemia vera.”

Alessandro M. Vannucchi, MD, of Azienda Ospedaliera–Universitaria Careggi, University of Florence, is the corresponding author for The New England Journal of Medicine article.

The study was funded by the National Cancer Institute, Novartis, and Incyte. For full disclosures of the study authors, visit

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