Efficacy and safety of a three-step dose escalation regimen of ropeginterferon alfa-2b in Japanese patients with polycythemia vera: a phase 3b, single-arm, multicenter study.
Key claim: A three-step accelerated dose escalation regimen of ropeginterferon alfa-2b (250→350→500 µg over 4 weeks) achieved a 57.1% complete hematologic response rate at week 24 in Japanese PV patients without additional safety concerns compared to the standard slower titration.
Abstract
Ropeginterferon alfa-2b, a monopegylated interferon α-2b, is a cytoreductive treatment for polycythemia vera (PV). In Japan, the current regimen involves titration in 50-µg increments every 2 weeks until reaching the maximum dose (500 µg), which requires considerable time. This phase 3b, open-label, single-arm, multicenter study (October 2023-July 2024) assessed the efficacy and safety of a three-step dose escalation regimen (day 1: 250 µg, week 2: 350 µg, week 4: 500 µg) of ropeginterferon alfa-2b in Japanese patients with PV (NCT06002490). Twenty-one patients were included (mean age: 57 years); most (95.2%) received ropeginterferon alfa-2b for at least 24 weeks. The complete hematologic response rate (primary endpoint; hematocrit < 45%, no phlebotomy in the previous 12 weeks, platelet count ≤ 400 × 10/L, and white blood cell count ≤ 10 × 10/L) was 23.8% (95% confidence interval 8.2, 47.2) at week 12 and 57.1% (34.0, 78.2) at week 24. Most patients (90.5%) reached the maximum dose of 500 µg by week 4. All patients had treatment-emergent adverse events, but none led to death, treatment discontinuation, or study withdrawal. This three-step dose escalation regimen of ropeginterferon alfa-2b has the potential to provide faster therapeutic effects in patients with PV without additional safety concerns.
Why this matters
Ropeginterferon alfa-2b is increasingly positioned as frontline therapy for PV, but slow dose titration delays time to hematologic and molecular response. Demonstrating that an accelerated three-step escalation reaches CHR in over half of Japanese PV patients by week 24 without new safety concerns refines the practical dosing arm of PV natural history management and adds population-specific evidence for East Asian patients, who have been underrepresented in pivotal PROUD/CONTINUATION-PV cohorts.