Ropeginterferon Alfa-2b Produces Responses, Safety in Prefibrotic Primary Myelofibrosis

Treatment with ropeginterferon alfa-2b (P1101) generated responses and was well tolerated in patients with prefibrotic primary myelofibrosis or low- or intermediate-1–risk myelofibrosis per the Dynamic International Prognostic Scoring System (DIPSS), according to data from the ongoing phase 2 P1101MF trial (NCT04988815) presented at the 2023 EHA Congress.

At a median follow-up of 14.8 months, 94% of patients (n = 61) completed 12 weeks of treatment, 91% (n = 59) completed 24 weeks of treatment, and 72% (n = 47) completed 48 weeks of treatment. Five patients discontinued treatment due to progressive disease (n = 3), pruritis (n = 1), or voluntarily withdrew (n = 1). No deaths, transformations to acute myeloid leukemia, or vascular events were reported.

Among patients who complete 24 weeks of treatment, the rates of hemoglobin responses, white blood cell responses, and platelet responses were 76.3%, 83.1%, and 76.3%, respectively. For patients evaluable at 48 weeks, those rates were 83.0%, 83.0%, and 72.3%, respectively.

Additionally, 50% of patients with JAK2 V617F mutations (n = 38) experienced reductions in mutant allele frequency (MAF), 26% experienced at least a 50% reduction, and 8% had a complete molecular response. Among those with CALR mutations (n = 16), 44% achieved reductions in MAF, and 6% had at least a 50% reduction in MAF.

“We observed early responses at 12 and 24 weeks of treatment, with complete molecular responses observed in [3] patients. That's a significant signal that this agent is performing its role as a disease modifier,” lead study author Harry Gill, MD, said.

In an interview with OncLive®, Gill, a clinical associate professor of Hematology in the Department of Medicine at the University of Hong Kong, discussed the rationale for exploringropeginterferon alfa-2b as a potential treatment option for patients early myelofibrosis and expanded on the efficacy and safety data observed in the phase 2 study.

OncLive: What was the rationale to investigate ropeginterferon alfa-2b in patients with myelofibrosis?

Gill: [For patients] with prefibrotic primary myelofibrosis, as well as [those with] low- and intermediate-1–risk myelofibrosis by the DIPSS, there is currently no approved treatment in these particular patient populations. Most often, these patient populations will be observed or cytoreduced with oral chemotherapy. Only a small portion of these patients might benefit from JAK inhibitors if they have symptomatic splenomegaly.

Therefore, the rationale [for this study] was that there is an important treatment need in this group of patients. Low-risk myelofibrosis may not actually be low-risk, because [these patients] are at a significant risk of vascular events. Therefore, they would need cytoreduction. In fact, these patients are diagnosed at an earlier age, and ultimately, in most of these patients, you might see disease progression.

It is important that in these populations, especially in younger individuals, that we consider not only control of blood counts and preventing [complications], but also disease modification. These were the things we wanted to [achieve] in this particular study.

Can you expand on the agent ropeginterferon alfa-2b, and why this was investigated within this patient population?

Ropeginterferon alfa-2b was specifically designed for patients with myeloproliferative neoplasms. This agent is given subcutaneously every 2 weeks because of its long half-life. Compared to older versions of interferon, [ropeginterferon alfa-2b] has a higher potency or activity against the malignant hematopoietic stem cells. That was the rationale for [investigating] possible disease modification [with the use of ropeginterferon alfa-2b].

Could you expand on the key efficacy findings from the P1101MF trial presented at the 2023 EHA Congress?

The key finding was that [approximately] 80% of patients achieved hematologic responses [at weeks 24 and 48]. Most of the patients were still in their first couple years of their treatment, and we have already observed significant hematologic responses. There were no thrombotic events throughout this period of follow-up.

The important findings that we wanted to point out would be the molecular responses. Twenty-six percent] of the patients who were JAK2 V617F positive and [6% of patients] who were CALR mutated had more than a 50% reduction in their MAF, which was remarkable.

What was found regarding toxicities?

As far as safety is concerned, [ropeginterferon alfa-2b] was tolerable without specific safety signals that were observed. The most common non-hematologic toxicities were hair loss, which was mostly grade 1 or grade 2 and didn't lead to any discontinuations. Additionally, anemia occurred in [42%] of patients, who were mostly amenable to dose modifications.

An important thing to note is that our dosing regimen [ramped up to] a higher dose following initial [treatment]. We began with 250 µg [in week 1]; subsequently, at 2 weeks, we switched to 350 µg, and at 4 weeks, we switched to 500 µg. The 500-µg dose was given every 2 weeks [thereafter], and that was a similar regimen to the ongoing [phase 3] SURPASS ET study [NCT04285086] in patients with essential thrombocythemia. Patients are tolerating this quite well, and we are observing early molecular responses.

What next steps will be taken for investigating this agent in patients with myelofibrosis?

The next step would be to investigate this agent in a randomized trial setting to define the specific efficacy and role of this agent in this population of patients.

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. Presented at: 2023 European Hematologic Association Annual Meeting; June 8-11, 2023; Frankfurt, Germany. Abstract S211.