SURPASS-ET topline results: Ropeginterferon alfa-2b vs anagrelide for ET

Hydroxyurea and anagrelide remain the standard treatments for essential thrombocythemia (ET), with no new therapy approved in the US since anagrelide. Ropeginterferon alfa-2b (ropeg) is a novel interferon-based therapy approved for polycythemia vera due to its cytoreductive efficacy and direct anticlonal activity. During the 2025 ASCO Annual Meeting, Ruben Mesa presented topline results from the phase III SURPASS-ET trial (NCT04285086), which assessed the safety and efficacy of ropeg vs anagrelide in patients with ET.¹

Patients diagnosed with high-risk ET (WHO 2016 criteria) who were either resistant or intolerant to hydroxyurea and were IFN-α naïve were eligible (N = 174). Patients were randomized 1:1 to receive ropeg SC, Q2W (n = 91) or oral anagrelide (n = 83). The primary endpoint was modified ELN response at 9 and 12 months. Secondary endpoints included JAK2V617F and CALR allele burden, symptom improvements based on MPN-SAF TSS, thromboembolic events, and safety.

Key learnings

A higher proportion of patients in the ropeg group achieved a modified ELN response compared to anagrelide (42.9% vs 6.0%; p = 0.0001). Response rates for individual ELN parameters were higher for ropeg vs anagrelide.

In the ropeg group, mean JAK2V617F allele burden decreased from 33.7% at baseline to 25.3% at 12 months, while in the anagrelide group, it increased from 37.3% at baseline to 39.7% at 12 months.

Ropeg vs anagrelide showed higher ≥25% symptom reduction in 58.4% vs 46.5% and ≥50% symptom reduction in 53.2% vs 39.5% of patients at 12 months.

Major ET-related thrombotic and cardiovascular events were lower in the ropeg vs anagrelide groups (1.1% vs 10.0% and 0% vs 7.5%, respectively).

The safety profile of ropeg was comparable to anagrelide, with Grade ≥3 TEAEs occurring in 23.1% vs 33.8% of patients, while TESAEs occurred in 14.3% vs 30.0% of patients, respectively.

Ropeg shows superior efficacy and safety as a second-line therapy for ET compared with anagrelide, offering a potential therapeutic option for patients with high-risk ET, with further investigation warranted.