Long-Term Ropeginterferon Alfa-2b Safe, Effective for Polycythemia Vera

Treatment with ropeginterferon alfa-2b demonstrates improved responses over time in comparison to hydroxyurea for polycythemia vera (PV), according to results from the phase 3 noninferiority trial, PROUD-PV, and its extension study, CONTINUATION-PV (Lancet Haematol. 2020 Jan 31. Epub ahead of print).

Ropeginterferon alfa-2b vs Hydroxyurea

“The PROUD-PV and CONTINUATION-PV trials aimed to compare the novel monopegylated interferon ropeginterferon alfa-2b with hydroxyurea…over 3 years of treatment,” explained Heinz Gisslinger, MD, Department of Internal Medicine I, Division of Haematology and Blood Coagulation, Medical University Vienna, Austria, and colleagues.

These phase 3 trials were conducted at 48 clinics across Europe and enrolled a total of 306 patients with early stage PV from September 17, 2013, to March 13, 2015. Patients were randomized in a 1:1 ratio to receive subcutaneous ropeginterferon alfa-2b every 2 weeks starting at 100 μg or oral hydroxyurea starting at 500 mg daily. Patients were able to opt into the extension portion of the trial, CONTINUATION-PV, after 1 year.

The primary end point of PROUD-PV was noninferiority of ropeginterferon alfa-2b in comparison with hydroxyurea with regard to hematologic response and normal spleen size at 12 months. The primary end points of CONTINUATION-PV were complete hematologic response with normalization of spleen size and improved disease burden.

The PROUD-PV and CONTINUATION-PV Trials

Overall, 257 patients were randomized in the PROUD-PV, including 127 in the repeginterferon-alfa-2b arm and 130 in the hydroxyurea arm; 3 patients ultimately withdrew consent from the latter arm.

A total of 171 patients then opted into the CONTINUATION-PV expansion portion of the trial. The median follow-up was 182.1 weeks in the ropeginterferon alfa-2b arm versus 164.5 weeks in the hydroxyurea arm.

Final results of PROUD-PV showed that 26 (21%) of 122 patients who received ropeginterferon alf-2b and 34 (28%) of 123 patients given hydroxyurea met the primary end point of complete hematologic response and normal spleen size.

At the 36-week interim analysis of CONTINUATION-PV, complete hematologic response with improved disease burden was achieved in 50 (53%) of 95 patients in the ropeginterferon alfa-2b arm and 28 (38%) of 74 patients in the hydroxyurea arm (P = .044).

Complete hematologic response, without normalization of spleen size, was achieved in 53 (43%) of 74 patients in the ropeginterferon alfa-2b arm and 57 (46%) of 125 patients in the hydroxyurea arm at 12 months in PROUD-PV (P = 0.63). The same was achieved in 67 (71%) of 95 patients versus 38 (51%) of 74 patients, respectively, at 36 months in CONTINUATION-PV trial (P = .012).

Adverse Events and Clinical Outcomes

The most common grade 3 and 4 treatment-related adverse events (AEs) were increased γ-glutamyltransferase (6%) and increased alanine aminotransferase (3%) in the ropeginterferon alfa-2b arm, and leucopenia (5%) and thrombocytopenia (4%) in the hydroxyurea arm. Serious treatment-related AEs occurred in 3 (2%) patients in the ropeginterferon alfa-2b arm and 5 (4%) patients in the hydroxyurea arm, and 1 treatment-related death due to acute leukemia was reported in the hydroxyurea arm.

“In patients with early polycythemia vera, who predominantly presented without splenomegaly, ropeginterferon alfa-2b was effective in inducing haematological responses; non-inferiority to hydroxyurea regarding haematological response and normal spleen size was not shown at 12 months,” Dr Gisslinger et al reported.

“However, response to ropeginterferon alfa-2b continued to increase over time with improved responses compared with hydroxyurea at 36 months,” they added, noting that ropeginterferon alfa-2b is a safe, valuable long-term therapy option based on its high and durable hematologic and molecular responses and good tolerability.—Janelle Bradley