Ropeginterferon alfa-2b versus anagrelide for the treatment of essential thrombocythemia: Topline results of the phase 3 SURPASS-ET trial.

6500 Background: BCR::ABL1 -negative myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF). No new treatments have been approved for ET in the US since anagrelide in 1997. Ropeginterferon alfa-2b (ropeg) is an anti-clonal interferon-based therapy approved by the FDA and globally for PV, providing the rationale for evaluation in ET and other MPNs. Methods: SURPASS ET is an open-label, multicenter, Phase III trial comparing ropeg with anagrelide over 12 months in patients with ET who were hydroxyurea-resistant or-intolerant. A total of 174 patients were randomized in a 1:1 ratio to receive ropeg or anagrelide. Ropeg was administered at 250 mcg at Week 0 titrating to 350 mcg at Week 2 and 500 mcg from Week 4 if tolerated. The primary endpoint was the rate of response, as defined by the Modified European LeukemiaNet response criteria, at both Months 9 and 12. Secondary endpoint assessments included JAK2 V617F allele burden, MPN-associated symptoms, thromboembolic events, spleen size, and safety. Results: Baseline patient characteristics were balanced across treatment arms (Table 1). The primary endpoint was achieved in 42.9% of patients in the ropeg arm versus 6.0% in the anagrelide arm (p=0.0001). Ropeg showed response improvements by each parameter: 1) Platelets ≤400x10 9 /L and white blood cells <9.5x10 9 /L: 56.0% vs. 6.0%. 2) Improvement or stabilization of splenomegaly: 87.9% vs. 54.2%. 3) Symptom improvement or stabilization: 71.4% vs. 33.7%. 4) Absence of hemorrhagic/thrombotic events: 84.6% vs. 51.8%. ET-related major thrombotic and cardiovascular events occurred in 1 (1.1%), and 0 patients in the ropeg arm vs. 7 (8.8%) and 6 (7.5%) patients, respectively, in the anagrelide arm. Mean JAK2 V617F allelic burden decreased from 33.7% at baseline to 25.3% at 12 months (ropeg arm) vs. 39.7% to 37.3% (anagrelide arm). Ropeg showed lower rate of adverse event (AE)-related discontinuation (5.5% vs.18.8%) and treatment-related serious AEs (2.2% vs. 10.0%). Conclusions: Ropeg showed superior efficacy and safety compared to anagrelide as second-line therapy for ET. It represents a potential new therapeutic option for ET. Clinical trial information: NCT04285086 . Patient demographics and baseline characteristics. Ropeg (n*=91) Anagrelide (n=83) Total (N=174) Age, y 61 (21-80) 64 (20-83) 63 (20-83) Race, x (%)CaucasianAsian 586 281 7167 Gender, x (%)FemaleMale 47 (52)44 (48) 44 (53)39 (47) 91 (52)83 (48) Total symptom score at baseline (MPN-SAF) 9 (0, 71) 9 (0, 74) 9 (0. 74) Spleen length by ultrasound, cm 13.1 (5.2-16.3) 15.2 (9.2-23.4) 13.9 (5.2-23.4) Leukocytes, x10 9 /L 11.4 (7.2-47.7) 11.6 (7.2-75.9) 11.5 (7.2-75.9) Platelets, x10 9 /L 942 (384-2132) 870 (406-4199) 925 (397-4199) JAK2 V617F, x (%) 72 (79) 70 (84) 142 (82) CALR exon 9, x (%) 11 (12) 10 (12) 21 (12) *n (%) presented for categorical variables. Median (range) for continuous variables.