Ropeginterferon alfa-2b for prefibrotic myelofibrosis and lower-risk myelofibrosis requiring cytoreduction

Clinical Snapshot

Key Findings

• P Value: Not reported in abstract

• Effect Size: CHCR rates: pre-PMF 74-78.4%, fibrotic PMF 20-33.3%, fibrotic SMF 42.9-53.9%

• Primary Outcome: CHCR achieved in 63.8% at week 24, 63.5% at week 48, and 70% at week 104

• Nnt Or Sensitivity: JAK2V617F VAF reduction in 53.1-70% of patients; CALR VAF reduction in 40-52.6% of patients

• Confidence Interval: Not reported in abstract

Clinical Application

Requires specialised haematology expertise for patient selection, monitoring, and dose adjustments. Subcutaneous administration every 2 weeks is practical for outpatient management Would require TGA approval and PBS listing for accessibility. Aligns with current RACGP guidelines for specialist referral of suspected myeloproliferative neoplasms. Cost-effectiveness assessment needed for PBS consideration Patients with early-stage myelofibrosis (prefibrotic or low-intermediate risk) requiring cytoreduction, particularly those intolerant of or inadequately responding to hydroxyurea

Abstract

There is currently no consensus on the optimal treatment of early myelofibrosis (MF). Ropeginterferon alfa-2b (ropeg) is a next-generation monopegylated interferon alfa-2b developed specifically to treat myeloproliferative neoplasms. We conducted a phase 2 study in patients with prefibrotic primary MF (pre-PMF) and Dynamic International Prognostic Scoring System low-/intermediate-1-risk fibrotic PMF or secondary MF (SMF) who required cytoreduction. Ongoing treatment with hydroxyurea was substituted with ropeg (week 0, 250 μg; week 2, 350 μg; week 4 onward, 500 μg every 2 weeks). The primary end points were safety and clinicohematologic complete response (CHCR). Seventy-one patients (40 men and 31 women) with a median age of 60 years (range, 31-86) were enrolled and followed up for a median of 119 weeks (range, 10-131). At weeks 24, 48, and 104, CHCR was achieved in 63.8% (pre-PMF, 74%; fibrotic PMF, 20%; fibrotic SMF, 42.9%), 63.5% (pre-PMF, 69.6%; fibrotic PMF, 25%; SMF, 53.9%), and 70% of patients (pre-PMF, 78.4%; fibrotic PMF, 33.3%; SMF, 50%), respectively. Thrombo-hemorrhagic events were not observed after stopping hydroxyurea. At weeks 24, 48, and 104, reduction in JAK2V617F variant allele frequency (VAF) was observed in 53.1%, 70%, and 67.6% of patients, and reduction in CALR mutant VAF was observed in 52.6%, 42.9%, and 40% of patients, respectively. In 50 evaluable cases at week 104, 13 patients (26%) had reduced bone marrow reticulin fibrosis. There were 3 treatment discontinuations (4.2%) due to adverse events. In conclusion, ropeg was safe and induced CHCR associated with significant molecular responses in patients with early MF. This trial was registered at www.clinicaltrials.gov as NCT04988815.

References

1. 1.Gill, H., Au, L., Yim, R., Lee, P., Li, V., Chin, L., Zhang, Q., Chan, P. Y., Lee, C. Y. Y., Wu, T. K. Y., Leung, G. M. K., & Kwong, Y. L. (2026). Ropeginterferon alfa-2b for prefibrotic myelofibrosis and lower-risk myelofibrosis requiring cytoreduction. Blood Advances. https://doi.org/10.1182/bloodadvances.2026019612