According to new results from the PROUD-PV (EudraCT number: 2012-005259-18) and CONTINUATION-PV studies (EudraCT number: 2014-001357-17), ropeginterferon alfa-2b appears to be more efficacious than the current standard cytoreductive therapy, hydroxyurea, at achieving durable hematologic and molecular remissions and was well tolerated in patients with polycythemia vera. The study authors suggested a change in treatment algorithms for polycythemia vera, with ropeginterferon alfa-2b replacing hydroxyurea as first-line cytoreductive therapy.
In the report, which was published in The Lancet Haematology, the researchers shared the final results of PROUD-PV and the interim results of the extension study CONTINUATION-PV at 36 months. The studies compared treatment using the novel monopegylated interferon ropeginterferon alfa-2b with hydroxyurea in adult patients with early polycythemia vera.
The phase 3, randomized, controlled trials were conducted at 48 clinics across Europe. Patients were randomly assigned in a 1:1 fashion to receive ropeginterferon alfa-2b (starting at 100 μg every 2 weeks, subcutaneously) or hydroxyurea (starting at 500 mg/day, orally). After 1 year on the PROUD-PV study, patients could elect to continue in the CONTINUATION-PV extension study.
In PROUD-PV, the primary end point was noninferiority of ropeginterferon alfa-2b compared with hydroxyurea for complete hematologic response with normal spleen size at 1 year. In CONTINUATION-PV, the primary end points were complete hematologic response with normalization of spleen size and improved disease burden.
Between September 2013 and March 2015, 306 patients were enrolled in the study. Ultimately, 257 patients were randomly assigned to the 2 treatment groups (127 each; 3 withdrew consent), and 171 patients opted for the CONTINUATION-PV trial. Median follow-up was 182.1 weeks (interquartile range [IQR], 166.3-201.7) and 164.5 weeks (IQR, 144.4-169.3) in the ropeginterferon alfa-2b group and the hydroxyurea group, respectively.
For the primary end point of PROUD-PV, 21% (26/122) of patients in the ropeginterferon alfa-2b group and 28% (34/123) of patients in the hydroxyurea group achieved complete hematologic response with normal spleen size (P =.23).
In the extension study, 53% (50/95) of patients in the ropeginterferon alfa-2b group and 38% (28/74) of patients in the hydroxyurea group achieved complete hematologic response with improved disease burden at 36 months (P =.044).
In the ropeginterferon alfa-2b group, the most frequently reported grade 3 to 4 treatment-related adverse events were increased gamma-glutamyltransferase (6%, 7/127) and increased alanine aminotransferase (3%, 4/127), while in the hydroxyurea group, they were leukopenia (5%, 6/127) and thrombocytopenia (4%, 5/127). One treatment-related death occurred in the hydroxyurea group.
“[R]opeginterferon alfa2b offers a new treatment option for patients with polycythaemia vera that has greater benefits than standard therapy with hydroxyurea after the second year of exposure, suggesting that ropeginterferon alfa2b treatment should be considered as early as possible in the course of disease,” concluded the researchers.
Disclosures: Some authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
1. Gisslinger H, Klade C, Georgiev P, et al. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study [published online January 31, 2020]. Lancet Haematol. doi: 10.1016/S2352-3026(19)30236-4