Background
PROUD-PV (phase 3, non-inferiority) and its extension CONTINUATION-PV enrolled 257 patients with early-stage polycythemia vera (cytoreductive-naive or <3 years of prior hydroxyurea), comparing ropeginterferon alfa-2b vs hydroxyurea. All patients received low-dose aspirin unless contraindicated.
Interventions and follow up
Arm A: Ropeginterferon alfa-2b SC every 2 weeks (titrated up to 500 ug)
Arm B: Hydroxyurea, standard dose (best available treatment in extension)
Crossover: After 1 year, 171 patients entered CONTINUATION-PV (95 continued ropeginterferon; 76 received best available treatment)
Primary endpoint: Complete hematologic response with normal spleen size at 12 months (PROUD-PV); complete hematologic response with improved disease burden at 36 months (CONTINUATION-PV)
Median follow-up: 36 months
Arm B: Hydroxyurea, standard dose (best available treatment in extension)
Crossover: After 1 year, 171 patients entered CONTINUATION-PV (95 continued ropeginterferon; 76 received best available treatment)
Primary endpoint: Complete hematologic response with normal spleen size at 12 months (PROUD-PV); complete hematologic response with improved disease burden at 36 months (CONTINUATION-PV)
Median follow-up: 36 months
Results
PROUD-PV (12 mo) complete hematologic response with normal spleen size: 21% (Arm A) vs 28% (Arm B) — met non-inferiority
PROUD-PV complete hematologic response (without spleen criterion): 43% vs 46%, P=.63
CONTINUATION-PV (36 mo) complete hematologic response with improved disease burden: 53% vs 38%, P=.044
CONTINUATION-PV complete hematologic response (without spleen criterion): 71% vs 51%, P=.012
PROUD-PV complete hematologic response (without spleen criterion): 43% vs 46%, P=.63
CONTINUATION-PV (36 mo) complete hematologic response with improved disease burden: 53% vs 38%, P=.044
CONTINUATION-PV complete hematologic response (without spleen criterion): 71% vs 51%, P=.012
Adverse events
Overall: Grade ≥3 adverse events 34% (Arm A) vs 27% (Arm B); treatment-related serious adverse events 2% vs 4%; discontinuation 8% vs 4%
Grade ≥3 events of note: Increased GGT 6% vs 2%; increased ALT 3% vs 0%; thrombocytopenia 2% vs 4%; leukopenia 2% vs 5%
Grade ≥3 events of note: Increased GGT 6% vs 2%; increased ALT 3% vs 0%; thrombocytopenia 2% vs 4%; leukopenia 2% vs 5%
Conclusions
Ropeginterferon alfa-2b achieved durable hematologic and molecular responses and was non-inferior, then superior over time, to hydroxyurea, offering a safe long-term cytoreductive option for polycythemia vera.
Key Limitations
Open-label design with composite, evolving primary endpoints across the two trial phases complicates interpretation. Slow ropeginterferon titration may have delayed early responses. The trial was not powered for thrombosis or long-term survival outcomes.
Clinical Context
PROUD-PV/CONTINUATION-PV supported FDA and EMA approval of ropeginterferon alfa-2b (Besremi) for polycythemia vera. It is a recognized cytoreductive option, particularly for younger patients and those seeking disease modification, alongside hydroxyurea per ESMO guidance.