Phase II Study Evaluates Ropeginterferon Alfa 2b in Lower-Risk, Early Primary Myelofibrosis

Ropeginterferon alfa 2b was “generally well tolerated” and induced “early” molecular responses in patients who have lower-risk early or prefibrotic stage primary myelofibrosis with a JAK2 V617F mutation, according to a recent study.

Harry Gill, MBBS, MD, of the University of Hong Kong, and colleagues conducted the research and presented their findings during the 2023 European Hematology Association Congress.

They conducted the research because there is “currently no optimal consensus on the optimal treatment” for patients with low-risk or intermediate-1-risk early stage or prefibrotic stage primary myelofibrosis, according to Dr. Gill and colleagues.

Ropeginterferon alfa 2b, also known as P1101, is a next-generation monopegylated interferon alfa-2b that was “developed specifically” to treat myeloproliferative neoplasms (MPN), according to the study’s authors.

The ongoing multicenter phase II study of ropeginterferon alfa 2b included patients with morphologically confirmed early or prefibrotic stage primary myelofibrosis, as well as those with overt primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis. Patients had low-risk or intermediate-1 risk disease and a need for cytoreduction.

The study included 36 men and 26 women with a median age of 59 years. Most patients had early or prefibrotic primary myelofibrosis (71%), while 9.7% had overt primary myelofibrosis, 8.1% had post-polycythemia vera primary myelofibrosis, and 11.3% had post-essential thrombocythemia myelofibrosis. Most patients (69.4%) had a JAK2 V617F mutation. The median time from diagnosis to treatment was five months. The baseline median MPN Symptom Assessment Form Total Symptom Score was 16.

The study’s primary outcome was hematologic responses at 24 and 48 weeks. Its secondary outcomes included adverse events (AEs), changes in allele burden of driver and nondriver gene mutations, quality of life, cytokine profiles, and bone marrow morphology.

Patients received a starting dose of ropeginterferon alfa 2b 250 mcg, followed by a dose of 350 mcg at week two. They received a dose of 500 mcg every two weeks from week four onwards.

At a median follow-up of 55 weeks, 90% of patients completed 24 weeks of treatment and 56% completed 48 weeks of treatment. At 24 weeks, 76.6% of patients had hemoglobin responses, 87.2% had white blood cell responses, and 78.7% had platelet responses. Nearly all (92%) of the 39 patients with a JAK2 V617F mutation showed a “stable or improved” JAK2 V617F allele burden, according to Dr. Gill and colleagues. One patient achieved undetectable JAK2 V617F from week 16 onwards.

Malaise was the most common AE, reported in 47%. Other common AEs included anemia in 42% of patients and hair loss in 37%. Asymptomatic derangement thyroid function occurred in 13%.

The researchers reported that three treatment discontinuations occurred, including two due to personal reasons and one due to symptom progression. None of the early stage or prefibrotic stage primary myelofibrosis cases progressed to overt primary myelofibrosis, the researchers reported. They did not observe any progressions to blast phase.

“In summary, P1101 was generally well-tolerated, effective in cytoreduction, and induced molecular responses early in JAK2 V617F-mutated patients with pre-[primary myelofibrosis] and low/intermediate-1-risk PMF,” the study’s authors concluded.

Reference

Gill H, Au L, Tsai D, et al. Efficacy and safety of ropeginterferon alfa-2b for pre-fibrotic primary myelofibrosis and DIPSS low/intermediate-1 risk myelofibrosis: updated results and genomic characteristics. Abstract #S211. Presented at the 2023 European Hematology Association Congress. June 8-15, 2023; Frankfurt, Germany.