Clinical Summary:

• Design/Population: This extended analysis of the phase 3 SURPASS-ET trial evaluated patients with high-risk essential thrombocythemia and leukocytosis after hydroxyurea failure. Patients initially received ropeginterferon alfa-2b or anagrelide, with eligible patients assigned to anagrelide able to crossover to ropeginterferon alfa-2b after the first year. 
• Key Outcomes: Ropeginterferon alfa-2b produced sustained  modified European LeukemiaNet responses through 2 years. Continuous treatment was associated with progressively deeper reductions in JAK2 V617F variant allele frequency, while patients initially receiving anagrelide experienced increasing molecular burden that began to rewverse after switiching to ropeginterferon alfa-2b.  
• Clinical Relevance: These findings strengthen evidence that ropeginterferon alfa-2b may provide benefits beyond hematologic control in high-risk essential thrombocythemia. The deeper molecular reductions observed with earlier, continuous treatment support its potential to modify the underlying disease burden after hydroxyurea failure. 

Extended results from the phase 3 SURPASS-ET trial demonstrated durable hematologic responses and progressively deeper molecular responses with ropeginterferon alfa-2b among patients with high-risk essential thrombocythemia following hydroxyurea failure. 

These results were presented by Lucia Masarova, MD, MD Anderson Cancer Center, Houston, Texas, at the Society of Hematological Oncology (SOHO) Annual Meeting in Houston, Texas.

In this open-label, multicenter trial conducted across 55 sites, researchers enrolled eligible patients with high-risk essential thrombocythemia and leukocytosis, defined as a white blood cell count greater than 10 × 10^9/L, following hydroxyurea failure. Patients were initially randomized 1:1 to receive either ropeginterferon alfa-2b or anagrelide. 

Ropeginterferon alfa-2b was initiated at 250 μg, increased to 350 μg at week 2, and subsequently administered at a maintenance dose of 500 μg every 2 weeks beginning at week 4. Anagrelide was administered according to its approved dosing regimen. After completing the first year of treatment, eligible patients initially assigned to anagrelide could cross over to ropeginterferon alfa-2b.

For the 24-month analysis, investigators evaluated patients who received continuous ropeginterferon alfa-2b as the early treatment cohort and patients who crossed over from anafrelide after the first year as the delayed treatment cohort. Key end points included sustained hematologic response, molecular changes, and progression-free survival (PFS). 

At 24 months, 84.6% of the 91 patients in the early cohort remained on treatment compared with 41% of the 83 patients initially assigned to anagrelide who comprised the delayed cohort. 

Modified European LeukemiaNet responses remained durable over the second year of treatment. Response rates were 49% and 32% at 15 months, 56.6% and 59.1% at 18 months, 62.1% and 41.7% at 21 months, and 58.6% and 62.5% at 24 months. 

Importantly, molecular responses continued to deepen with sustained ropeginterferon alfa-2b exposure. Among patients in the early cohort, mean JAK2 V617F variant allele frequency demonstrated an absolute reduction of 8.2% and a relative reduction of 19.1% after the first year. By the end of year 2, the absolute reduction had increased to 12.4%, with a relative reduction of 28.2%. 

A contrasting molecular trajectory was observed among patients who initially received anagrelide. During the first year, mean JAK2 V617F variant allele frequency increased by 3.5% in absolute terms and 13.2%, respectively. After patients crossed over to ropeginterferon alfa-2b, this pattern reversed, with an absolute variant allele frequency reduction of 1.4% and relative reduction of 5.2% by the end of the second year. 

Although switching from anagrelide to ropeginterferon alfa-2b was associated with reversal of the previous increase in JAK2 V617F VAF, the magnitude of molecular reduction remained smaller than that observed among patients who had received ropeginterferon alfa-2b continuously from study initiation.

The extended findings build upon the initial SURPASS-ET results, which established superior durable modified European LeukemiaNet responses with ropeginterferon alfa-2b compared with anagrelide after hydroxyurea failure. The 2-year analysis suggests that prolonged treatment may further influence the underlying mutant clone, with earlier exposure associated with deeper molecular responses.

Source:

Masarova L, Gill H, Qin A, et al. Efficacy and molecular dynamics of ropeginterferon alfa-2b in high-risk essential thrombocythemia: Two-year results from the phase 3 SURPASS-ET trial. Presented at the SOHO Annual Meeting; September 9-12, 2026; Houston, Texas. Abstract MPN-944.