Ropeginterferon Alfa-2B Versus Hydroxyurea in Patients With Polycythemia Vera

Treatment with ropeginterferon alfa-2B, a mono-pegylated proline interferon, reduced JAK2 allele burden in patients with polycythemia vera (PV) and appeared to modify the underlying disease, according to an analysis of the randomized, controlled, phase III PROUD-PV study. Unlike hydroxyurea (HU), a standard treatment for PV, ropeginterferon specifically targets JAK2 mutant progenitor cells, which contributes to a “strikingly different” JAK2 allele burden in patients’ peripheral blood (PB) and bone marrow (BM), as reported by the investigators, led by Jean-Jacques Kiladjian, MD, PhD, from Hôpital Saint-Louis in Paris, France.

Dr. Kiladjian presented results at the 22nd Congress of the European Hematology Association.

The PROUD-PV trial included 257 patients from 13 European countries who received either ropeginterferon alfa-2B or HU to assess the correlation between evolution of JAK2 V617F in PB and the effect of therapy on malignant clones in the BM.

For this analysis, the researchers looked specifically at the 13 patients enrolled from France (mean age = 55 years; range not provided) because that cohort had available data about bone marrow progenitor cells, specifically the presence or absence of erythropoietin. “The presence of colonies without erythropoietin is a hallmark of PV,” the authors noted.

In that group, five patients received ropeginterferon and eight received HU.

In the overall PROUD-PV population, ropeginterferon was non-inferior to HU for complete hematologic response (primary endpoint; per European LeukemiaNet criteria) at 12 months: 43.1 percent versus 45.6 percent (p value not provided). In the French group, rates were similar: 40 percent in those receiving ropeginterferon and 50 percent in those receiving HU (p value not provided).

Over the course of follow-up, all patients experienced a reduction in their JAK2 allele burden:

  • baseline: 39.4% (ropeginterferon group) and 46.5% (HU group)
  • 6 months: 29.1% and 25.8%
  • 12 months: 13.8% and 33.2%

No patients in either cohort achieved complete molecular response (MR; secondary endpoint), but partial MR was achieved in 40 percent of patients treated with ropeginterferon and 25 percent of patients treated with HU (p value not provided).

Ten patients had data on BM progenitor cells available (3 in the ropeginterferon group and 7 in the HU group). The authors observed that patients in the ropeginterferon group had a greater reduction in the proportion of colonies without erythropoietin (endogenous erythroid colonies) from baseline to 12 months, compared with those in the HU group (median decreases = 64% and 25%; ranges and p value not provided), indicating greater disease control.

In addition, clonal architecture analysis showed that all patients treated with ropeginterferon experienced a “profound decrease” in the percentage of JAK2 V617F mutant colonies: The mean ratio of mutant versus wild-type JAK2 colonies decreased from 96 percent at baseline to 46 percent at 12 months. In the HU-treated group, just one patient experienced a decrease (from 87% to 79%).

“Such targeted impact of [ropeginterferon] suggests that sustained long-term MR may only be achieved with interferon-alfa-based treatment,” the authors concluded.

The study is limited by its small patient population.

Dr. Kiladjian reports research funding from AOP Orphan Pharmaceuticals AG.


Kiladjian JJ, Cassinat B, Soret-Dulphy J, et al. Molecular response to hydroxyurea and ropeginterferon alfa-2B in the PROUD-PV randomized phase 3 trial. Abstract #S787. Presented at the 22nd Congress of the European Hematology Association, June 25, 2017; Madrid, Spain.