Ropeginterferon alfa-2b fares well for ET in ROP-ET trial

The results from the phase III ROP-ET trial demonstrate the potential of ropeginterferon alfa-2b (ropeg) for the treatment of essential thrombocythaemia (ET) across all risk levels in patients who are ineligible for standard cytoreduction.

“ROP-ET met its primary efficacy endpoint. At 12 months, 48 percent of participants showed a durable disease response according to the modified European LeukemiaNet criteria,” said Dr Jean-Jacques Kiladjian from the Université Paris Cité, Paris, France, at ASH 2025.

Looking at the individual components of the primary endpoint, none had disease progression, all but two had absence or non-progression in disease-related signs (splenomegaly), 96.2 percent had no haemorrhagic or thrombotic events, 84.2 percent had durable improvement or non-progression in disease-related symptoms, and two-thirds achieved durable peripheral blood count remission response.

Five patients experienced haemorrhagic or thrombotic events – two were major (acute myocardial infarction, transient ischaemic attack) and three were minor (soft tissue haemorrhage, superficial vein thrombosis, thrombophlebitis). [ASH 2025, abstract 485]

Among participants with a CALR mutation, disease response rates were 51.5, 53.1, and 68.8 percent at months 6, 9, and 12, respectively. Among those with a JAK2 mutation, the corresponding rates were 29, 54.3, and 64.3 percent.

Month 12 also saw reductions in median platelet (from 577 × 10⁹/L to 289.5 × 10⁹/L) and leukocyte (from 7.35 × 10⁹/L to 4.4 × 10⁹/L) counts relative to baseline, and nearly 90 percent of participants showed symptom improvement (62.3 percent) or non-progression (25.4 percent) as assessed by MPN-SAF TSS*.

The mean haemoglobin concentration remained stable from baseline (13.4 g/dL) to month 12 (13 g/dL).

Safety profile

Approximately 70 percent of participants reported treatment-related adverse events (TRAEs), but these were mostly mild, with only 5.3 percent having grade ≥3 TRAEs. Only one patient experienced serious TRAEs (thrombocytopenia, neutropenia).

The most frequently reported adverse drug reactions were headache and increased alanine aminotransferase (15.2 percent each) and neutropenia, pruritus, and increased gamma-glutamyltransferase (10.6 percent each).

“Ropeg was safe and well tolerated in ET patients, consistent with the experience in polycythaemia vera (PV). Treatment-related toxicity was mainly mild and rarely led to drug withdrawal (2.3 percent),” Kiladjian said.

A disease-modifying therapy is warranted

Most available therapies for ET primarily target platelet count reduction with no demonstrated effect on disease progression, Kiladjian noted. “Moreover, these treatments are often limited by intolerance, resistance, or contraindications, leaving a substantial proportion of patients without satisfactory therapeutic options.”

ET patients have a significant lifetime risk of disease progression, requiring a disease-modifying therapy. “Ropeg, a mono-pegylated, next-generation interferon alfa approved globally for PV with the potential to modify disease course, is being studied to address this unmet need,” he continued.

The study comprised adults with ET, according to the WHO 2016 criteria, in need of cytoreductive therapy, who were interferon-naïve and intolerant or resistant to, and/or ineligible for, all locally approved cytoreductive therapies, including hydroxyurea (HU), anagrelide (ANA), busulfan, and pipobroman.

A total of 132 participants (median age 56.5 years, 58.3 percent women) received ropeg subcutaneously Q2W starting at 125 μg. The dose can be escalated to 250 and 500 μg if needed to achieve a haematologic response. The mean 2-weekly dose over the first 12 months was 193.8 μg.

At baseline, 25.8 percent of patients had splenomegaly, and the median MPN-SAF TSS was 8. The most frequent driver mutation was JAK2 (60 percent), followed by CALR (27 percent). According to the IPSET-Thrombosis** risk stratification criteria, approximately 45 percent of participants had high-risk disease.

The most frequent prior cytoreductive therapy was HU + ANA (37.1 percent), followed by HU (31.8 percent) and ANA (13.6 percent). A quarter of pretreated patients had cytoreductive therapy resistance, while 72 percent developed intolerance.

“[Taken together,] ropeg appears to be a favourable therapeutic option for ET patients who require cytoreduction but cannot receive other available therapies,” Kiladjian said.