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

There is currently no consensus on the optimal treatment for 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 pre-fibrotic primary MF (pre-PMF), and dynamic international prognostic scoring system (DIPSS) low/intermediate-1 risk fibrotic PMF or secondary myelofibrosis (SMF), who required cytoreduction. Ongoing treatment with hydroxyurea was substituted with ropeg (week 0: 250 mcg; week 2: 350 mcg; week 4 onwards: 500 mcg every 2 weeks). The primary endpoints were safety and clinicohematological complete response (CHCR). Seventy-one patients (40 men and 31 women) with a median age of 60 (range: 31-86) years were enrolled, followed up for a median of 119 (range:10-131) weeks. 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% (pre-PMF: 78.4%; fibrotic PMF: 33.3%; SMF 50%) of patients. 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. ClinicalTrials.gov Identifier: NCT04988815