Dr Gill on the Efficacy and Genomic Features of Ropeginterferon Alfa-2B in Myelofibrosis

Harry Gill, MD, FRCP, FRCPath, clinical assistant professor, Department of Medicine, Li Ka Shing Faculty of Medicine, Hong Kong University of Medicine, discusses updated efficacy data and analysis of genomic characteristics of response with ropeginterferon alfa-2b(P1101) in primary myelofibrosis.

An ongoing multicenter phase 2 study (NCT04988815) was designed to assess the efficacy and safety of this next-generation monopegylated interferon in patients with early or pre-fibrotic myelofibrosis and those with low- or intermediate-1 risk myelofibrosis according to the Dynamic International Prognostic Scoring System. A total of 65 patients were enrolled in the trial. Patients were treated with a starting dose of 250 mcg of ropeginterferon alfa-2b, which was increased to 350 mcg at week 2 and 500 mcg biweekly beginning at week 4.

The primary end points were hematologic response at 24 and 48 weeks and adverse effects (AEs). Key secondary end points included changes in allele burden of driver and non-driver gene mutations, quality of life, cytokine profiles and bone marrow morphology.

Results showed that 76.3% and 83.1% of all patients achieved hemoglobin and white blood cell (WBC) count responses, respectively, with ropeginterferon alfa-2b at 24 weeks, and 76.3% experienced platelet responses, Gill reports. These rates were 83.0%, 83.0%, and 72.3% at 48 weeks. Responses were early, and hemoglobin, WBC and platelet levels remained stable, Gill says. Moreover, no thrombotic events were observed, Gill adds.

Regarding molecular responses, 76% of patients with JAK2 V617F mutations and 50% of those with CALR mutations experienced reductions in mutant allele frequency at 6 months, Gill continues. Of these, 26% of patients with JAK2 V617F mutations and 6% of those with CALR mutations experienced a 50% or greater reduction. Notably, 8% of patients with JAK2 V617F mutations achieved a complete molecular response, Gill emphasizes.

Regarding safety, the agent was well tolerated, he states. Additionally, no deaths, transformation to AML, or vascular events were reported. Five patients discontinued treatment.

These findings indicate that early administration of ropeginterferon alfa-2b is safe, active, and may allow for disease modification, Gill concludes.