New Long-Acting Interferon Effective and Safe in Polycythemia Vera
San Diego, CA—Ropeginterferon alfa-2b, an investigational, long-acting, mono-pegylated interferon was noninferior to hydroxyurea in achieving complete hematologic response and with superior tolerability to hydroxyurea in the treatment of patients with polycythemia vera, according to the final results of the phase 3 PROUD-PV clinical trial presented by Heinz Gisslinger, MD, Medical University of Vienna, Austria, at the 2016 American Society of Hematology meeting.
Ropeginterferon alfa-2b has received an orphan drug designation from the FDA; if approved, it would be the first interferon approved for the treatment of patients with polycythemia vera, and the only FDA-approved first-line treatment for polycythemia vera. Interferons have been used in polycythemia vera since the 1980s, but 25% of patients discontinue interferon treatment because of adverse events, noted Dr Gisslinger.
The long-term risk for disease progression in polycythemia vera is nearly 20%, and transformation to acute myeloid leukemia or myeloproliferative dysplastic syndrome occurs in 3% to 10% of patients with polycythemia vera.
“Results from this first and largest prospective controlled trial of an interferon in PV [polycythemia vera] confirm previously reported efficacy,” said Dr Gisslinger. “The observed safety and tolerability profile of ropeginterferon appears to be superior to previously reported data,” he added.
The PROUD-PV clinical trial was a randomized, open-label, multicenter, controlled, parallel-group study comparing ropeginterferon alfa-2b with hydroxyurea in 254 patients with polycythemia vera from 48 European centers.
Patients naïve to cytoreduction or those who received pretreatment with hydroxyurea but were neither intolerant to hydroxyurea nor complete responders after a treatment duration of <3 years were randomized to receive ropeginterferon alfa-2b every 2 weeks or hydroxyurea daily.
The prespecified primary end point was the noninferiority of ropeginterferon alfa-2b to hydroxyurea and a composite of complete hematologic response at 12 months of therapy with ropeginterferon alfa-2b or hydroxyurea. A complete hematologic response was defined as hematocrit <45% without phlebotomy (at least 3 months since the last phlebotomy), platelet count <400 G/L, normal spleen length, and leukocyte count <10 G/L. In each treatment group, 37% of patients received pretreatment with hydroxyurea, and the median spleen size was approximately 13 cm in each treatment group.
The median plateau dose was 450 µg for ropeginterferon alfa-2b and 1250 mg for hydroxyurea. Overall, 25.2% who received ropeginterferon alfa-2b required dose reduction as a result of adverse events versus 51.2% who received hydroxyurea. The discontinuation rates were 16.5% in the ropeginterferon alfa-2b group versus 12.6% in the hydroxyurea group.
At 12 months, 43.1% of patients who received ropeginterferon alfa-2b achieved complete hematologic response versus 45.6% of patients who received hydroxyurea in the intent-to-treat population (P = .0028), which met the criterion for noninferiority.
The inclusion of the change in spleen size in the primary end point was a potential confounder, because the median spleen length was nearly normal at baseline in both treatment arms. Therefore, the change in the median spleen length in the intent-to-treat population in either treatment arm was not clinically relevant (21.3% for ropeginterferon alfa-2b vs 27.6% for hydroxyurea; P = .2233).
Treatment-related adverse events occurred in 75.6% of patients who received hydroxyurea compared with 59.6% of patients who received ropeginterferon alfa-2b. There was no difference in the rate of adverse events of special interest regarding interferons (ie, autoimmune, psychiatric, and cardiovascular disorders). Throughout this phase 3 clinical trial, no secondary malignancies occurred with ropeginterferon alfa-2b, but 5 secondary malignancies (ie, 2 acute leukemias, 2 basal carcinomas, and 1 melanoma) occurred with hydroxyurea therapy.