HOPE-PMF Trial Set to Investigate Interferon-Based Therapy for Early and Low-Risk PMF

The soon-opening phase 3 HOPE-PMF trial will investigate the efficacy of interferon-based therapy, ropeginterferon alfa-2b (ropeg), for early and lower-risk primary myelofibrosis (PMF). The multicenter trial will include 150 participants randomized 2:1 to ropeg and placebo in a double-blind, placebo-controlled design.

Of the three major myeloproliferative neoplasms, PMF has the worst prognosis and symptoms. PMF causes high rates of anemia, splenomegaly, and bone marrow fibrosis. The standard-of-care Janus kinase 2 (JAK2) inhibitors are only approved for advanced MF and high-risk PMF, leaving watchful waiting as the recommended strategy for most early and lower-risk PMF, with no satisfactory, disease-modifying treatments on the market.¹ Ropeg is a long-acting monoPEGylated proline-interferon–based therapy that is FDA approved for use in treatment of polycythemia vera, where it improves survival and complete hematologic response. The current HOPE-PMF trial (NCT06468033) aims to evaluate the safety and efficacy of ropeg in the treatment of lower-risk and early PMF.²

HOPE-PMF will recruit 150 participants with prefibrotic PMF or PMF at low or intermediate-1 risk as defined by the Dynamic International Prognostic Scoring System (DIPSS). Participants will be randomized 2:1 to subcutaneous injections of ropeg or placebo every two weeks. The dosing will be escalated over time, starting with 250 µg in week 0, increasing to 350 µg in week 2, and continuing with 500 µg until week 56. On successful 4-week safety follow-up, participants of both groups will enter an extended 56-week treatment period. Co-primary endpoints at the first 56-week interval include a clinically relevant complete hematologic response and absence of symptom progression at 56 weeks. Secondary endpoints include survival (progression- or event-free), bone marrow response, safety, and molecular response. The study is expected to be completed in 2028.

REFERENCES:

1. Abu-Zeinah G, Qin A, Gill H, et al. A randomized, double-blind, placebo-controlled phase 3 study to assess efficacy and safety of ropeginterferon alfa-2b in patients with early/lower-risk primary myelofibrosis. Ann Hematol. 2024;103(9):3573-3583. doi: 10.1007/s00277-024-05912-8
2. Abu-Zeinah G, Qin A, Gill H, et al. HOPE-PMF: A randomized, double-blind, placebo-controlled phase 3 study to assess efficacy and safety of ropeginterferon alfa-2b in patients with early/lower-risk primary myelofibrosis. Abstract #3191.1. Presented at the ASH Annual Meeting December 7-10, 2024; San Diego, California.