e18592 Background: Ropeginterferon alfa-2b (ropeginterferon) is a mono-pegylated interferon-alpha that received FDA approval in 2021 as the first interferon for adults with polycythemia vera (PV). Dosing and titration schedule of ropeginterferon have varied across previous PV studies. Emerging evidence from clinical studies and real-world experience suggests that a higher initial dose and accelerated titration (HIDAT; starting at 250 µg and escalating from 250 to 350 to 500 µg within 4 weeks) may shorten time to hematologic and molecular responses compared with low initial dose and response-based titration (starting at 50-100 µg, increased by 50 µg every 2 weeks). However, whether the HIDAT regimen provides a meaningful advantage in efficacy and safety remains uncertain. Methods: We conducted a systemic review and meta-analysis in accordance with PRISMA guidelines. A total of 13,769 records were screened using key terms related to PV and ropeginterferon from MEDLINE, Embase, Web of Science, and ClinicalTrials.gov. We identified 18 studies, including randomized controlled trials, single-arm studies, and cohort studies, in which ropeginterferon was administered to adults (≥18 years) with PV. We compared HIDAT (starting dose ≥250 µg) versus low-dose regimens (<250 µg) by pooling single arms of ropeginterferon treatment. Analyses were performed using the meta package in R (version 7.0.0). Outcomes included complete hematologic response (CHR), molecular response (MR; European LeukemiaNet criteria, partial and complete combined), adverse events (AEs), and discontinuation rates in both dosing strategies. Results: HIDAT was associated with higher CHR rates at 3 months (33.5% vs 12.2%, P = 0.029), 6 months (49.6% vs 30.0%, P = 0.016), and 12 months (59.7% vs 31.6%, P = 0.0004), with no difference at 24 months (50.7% vs 54.5%, P = 0.76). Similarly, HIDAT produced significantly higher MR rates beginning at 6 months (38.4% vs 22.7%, P = 0.024), persisting at 12 months (52.7% vs 33.7%, P = 0.013). From a safety perspective, there was a higher incidence of grade ≥3 AEs at 12 months with HIDAT (12.7% vs 3.8%), albeit not statistically significant ( P = 0.157); these higher-grade AEs were primarily laboratory abnormalities (eg, hematologic cytopenias and transient elevation in liver enzymes) and were generally reversible with dose modification and temporary interruption. Discontinuation rates were comparable at 6 months (0% vs 1.1%, P = 0.997), 12 months (2.5% vs 2.6%, P = 0.942), and 24 months (1.6% vs 7.3%, P = 0.146). Conclusions: HIDAT may accelerate achievement of CHR and MR compared with conventional low-dose titration, without compromising overall safety. These findings support future studies to further evaluate the effectiveness and safety of the HIDAT regimen over the traditional low-dose regimen.
Yacoub et al. (Thu,) studied this question.