Real-World Evidence on Outcomes and Safety of Ropeginterferon Alfa-2b in Patients With Myeloproliferative Neoplasms: A Retrospective Cohort Study.

Abstract

Background: Ropeginterferon alfa-2b-njft (ropegIFN) has demonstrated superior efficacy over hydroxyurea in polycythemia vera (PV); however, real-world data on its application across Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPNs) remain limited.

Patients and methods: This retrospective cohort study included 64 patients with Ph- MPNs (15 PV, 16 essential thrombocythemia [ET], 5 prefibrotic myelofibrosis [preMF], and 28 with overt myelofibrosis [MF]) treated with ropegIFN between October 2018 and June 2024.

Results: After a median follow-up of 5.3 years, the hematological response (HR) rates at 36 months were 87% in PV, 75% in ET, 80% in preMF, and 45% in overt MF (P = .026). Best molecular response (MR) rates were 80% in PV, 69% in ET, 75% in preMF, and 47% in overt MF (P = .11). The median JAK2 variant allele frequency (VAF) declined significantly from 67.9% at baseline to 18.7% during follow-up (P < .001), with consistent reductions across MPN subtypes confirmed by GEE analysis. In patients with MF, neither HR nor MR was observed among those harboring high-molecular-risk (HMR) mutations (24-month HR: 0% vs. 72%; P = .002; 24-month MR: 0% vs. 18%; P = .4). Additionally, these patients exhibited a significantly higher cumulative incidence of adverse events (48% vs. 7%; P < .001).

Conclusions: RopegIFN demonstrated hematological and molecular efficacy across Ph- MPN subtypes and was generally well tolerated. However, its effectiveness appears limited in patients with MF, particularly those with high-molecular-risk (HMR) mutations. These findings support the potential disease-modifying role of ropegIFN and highlight the need for prospective multicenter studies to validate its long-term impact on disease progression and survival.