Phase 3 Essential Thrombocythemia Trial: Novel Interferon-Based Agent Superior to Anagrelide

The randomized phase 3 trial SURPASS ET has investigated the novel interferon-based therapy ropeginterferon alfa-2b for second-line management of essential thrombocythemia (ET). Researchers have determined that the agent in this setting has superior efficacy and safety compared to anagrelide.¹

Topline result data from the trial were released at the 2025 European Hematology Association (EHA) Congress in Milan, Italy. On-site, the trial’s first author, Harinder (Harry) Gill, MD, of the University of Hong Kong, presented findings during the Congress’ plenary session.²

Dr. Gill summarized the trial findings that ropeginterferon alfa-2b “presents a potential new therapeutic option for patients with high-risk ET.”²

SURPASS ET is an open-label, active-controlled, multicenter study that enrolled 174 patients with high-risk ET who had intolerance to hydroxyurea or whose disease had progressed despite that therapy. Following randomization, 91 patients received ropeginterferon alfa-2b, and 83 patients received anagrelide over 12 months. Patients in the ropeginterferon alfa-2b group received the agent at 250 mcg in Week 0, with a schedule to titrate to 350 mcg at Week 2, and then, if tolerated, to 500 mcg every 2 weeks from Week 4 onward.¹

The primary outcome of the trial was achieving a response at both months 9 and 12, as per the Modified European LeukemiaNet (ELN) criteria. This was achieved by 42.9% of ropeginterferon alfa-2b recipients versus 6.0% of anagrelide recipients (P=0.0001).¹

“As far as individual components of the ELN response is concerned, platelet, white count, control, peripheral blood count normalizations, improvements of splenomegaly, improvement in symptoms, and the absence of thrombotic complications, all in these areas there was significant improvement in the response rates of ropeg [ropeginterferon alfa-2b] over anagrelide,” Dr. Gill said during his presentation.²

Among the ropeginterferon alfa-2b recipients, no patients experienced disease progression to myelofibrosis or acute leukemia; in the anagrelide group, 8.8% of patients’ disease progressed to myelofibrosis and 3.6% to acute leukemia. One recipient of ropeginterferon alfa-2b experienced an ET-related thrombotic event.¹

Regarding changes in the JAK2V617F allele fraction by month 12 of the study in either study arm, in the ropeginterferon alfa-2b group, there was a decline from 33.7% to 25.3%, and in the anagrelide group, from 39.7% to 37.3%.¹

“The findings of molecular responses also corroborate with the disease-modifying potential of ropeginterferon alfa-2b,” Dr. Gill remarked. To answer an internet-submitted question during the presentation, Dr. Gill said the study team had not yet investigated whether the presence of additional mutations in patients affects their molecular or hematological responses.²

Comparing the ropeginterferon alfa-2b and anagrelide groups, the rates of treatment-related discontinuation in the trial were 4.4% and 12.5%, respectively. The rates of treatment-related serious adverse events (AEs) were 2.2% and 10.0%, respectively, and AEs of special interest were 27.5% and 43.8%, respectively. All psychiatric and ocular AEs that occurred among the study arms were of grade 1 or 2 severity.¹