Clinical Summary: 

• Design/Population: This systematic review and meta-analysis evaluated outcomes associated with high initial dose and accelerated titration of ropeginterferon alfa-2b compared with conventional low-dose titration in adults with polycythemia vera.
• Key Outcomes: High initial dose and accelerated titration was associated with significantly higher hematologic and molecular response rates during the first year of treatment, with similar discontinuation rates and no statistically significant increase in severe adverse events.
• Clinical Relevance: These findings suggest that accelerated ropeginterferon dosing may improve early disease control in polycythemia vera and support further prospective evaluation of this treatment strategy.

Results from a systematic review and meta-analysis demonstrated that high initial dose and accelerated titration of ropeginterferon alfa-2b was associated with faster hematologic and molecular responses compared with conventional low-dose titration among patients with polycythemia vera.

“Ropeginterferon is a mono-pegylated interferon-alpha that received FDA approval in 2021 as the first interferon for adults with polycythemia vera,” stated Abdulraheem Yacoub, MD, University of Kansas Center for Bioinformatics, Westwood, Kansas, and coauthors. However, “dosing and titration schedule of ropeginterferon have varied across previous [polycythemia vera] studies.” 

In this study, researchers collected data from adult patients enrolled across 18 randomized, single-arm, cohort studies assessing ropeginterferon. Higher initial dose and accelerated titration was defined as a starting dose of ≥ 250 µg with escalation from 250 µg to 350 µg to 500 µg within 4 weeks. Conventional dosing consisted of starting doses < 250 µg with response-based titration. Outcomes included complete hematologic response, molecular response, adverse events, and treatment discontinuation rates.

At analysis, higher initial dose and accelerated titration was associated with significantly higher complete hematologic response rates at 3 months (33.5% vs 12.2%; P = .029), 6 months (49.6% vs 30.0%; P = .016), and 12 months (59.7% vs 31.6%; P = .0004). By 24 months, complete hematologic response rates were similar (50.7% vs 54.5%; P = .76). Molecular response rates also favored higher initial dose and accelerated titration, with significantly higher rates observed at 6 months (38.4% vs 22.7%; P = .024) and 12 months (52.7% vs 33.7%; P = .013).

Grade ≥3 adverse events were reported in 12.7% of patients treated at higher initial dose and 3.8% of patients treated at conventional dosing (P = .157). These events primarily consisted of laboratory abnormalities, including cytopenias and transient elevations in liver enzymes, and were generally reversible with dose modification or treatment interruption. Treatment discontinuation rates were similar between dosing strategies at 6 months (0% vs 1.1%), 12 months (2.5% vs 2.6%), and 24 months (1.6% vs 7.3%).

“These findings support future studies to further evaluate the effectiveness and safety of the HIDAT regimen over the traditional low-dose regimen,” concluded Dr Yacoub et al. 

Source: 

Yacoub A, Imada S, Wu CT, et al. Effect of higher initial dose and accelerated titration of ropeginterferon alfa-2b on early hematologic and molecular responses in polycythemia vera: A meta-analysis. Presented at the 2026 ASCO Annual Meeting. Chicago, Illinois. Abstract e18592.