Background
SURPASS-ET: phase 3 open-label, randomized, active-controlled multicenter trial. 174 patients with high-risk essential thrombocythemia (age >60 with JAK2V617F OR history of disease-related thrombosis/hemorrhage) who were hydroxyurea-intolerant or refractory AND had leukocytosis (WBC >10×10⁹/L). Enrolled at 55 sites across China, Japan, Taiwan, Hong Kong, South Korea, USA, Singapore, and Canada; 96% Asian. Randomized 1:1 to ropeginterferon alfa-2b vs anagrelide.
Interventions and follow up
Arm A: Ropeginterferon alfa-2b 250 μg SC q2wks (titrated to 350 μg at week 2, then 500 μg from week 4)
Arm B: Anagrelide per FDA-approved prescribing information
Primary endpoint: Rate of durable modified ELN response at months 9 AND 12
Median follow up: 12.5 months
Arm B: Anagrelide per FDA-approved prescribing information
Primary endpoint: Rate of durable modified ELN response at months 9 AND 12
Median follow up: 12.5 months
Results
Durable ELN response at months 9 and 12: 43% vs 6%, difference 36.5% (95% CI 25.4–47.7), P=.0001
JAK2V617F allele burden change: 33.7% → 25.3% (ropeg) vs 39.7% → 37.3% (anagrelide)
Cerebral infarction: 0 (ropeg) vs 4 (5%) (anagrelide)
Any thrombotic/cardiovascular event: 1 (1.1%) ropeg vs 7 (8.8%) anagrelide
JAK2V617F allele burden change: 33.7% → 25.3% (ropeg) vs 39.7% → 37.3% (anagrelide)
Cerebral infarction: 0 (ropeg) vs 4 (5%) (anagrelide)
Any thrombotic/cardiovascular event: 1 (1.1%) ropeg vs 7 (8.8%) anagrelide
Adverse events
Grade ≥3 AEs: 23% ropeg vs 34% anagrelide; serious AEs 14% vs 30%; no treatment-related deaths in either arm
By system: most common grade ≥3 with ropeg was infections (9% vs 6%); with anagrelide, nervous system disorders (8% vs 1%)
Vascular: cerebral infarction in 4 anagrelide patients (5%) vs 0 ropeginterferon
By system: most common grade ≥3 with ropeg was infections (9% vs 6%); with anagrelide, nervous system disorders (8% vs 1%)
Vascular: cerebral infarction in 4 anagrelide patients (5%) vs 0 ropeginterferon
Conclusions
Ropeginterferon alfa-2b significantly outperformed anagrelide as second-line therapy for high-risk, HU-intolerant/refractory ET with leukocytosis, with 43% achieving durable ELN response at 9 and 12 months vs 6% with anagrelide. Ropeginterferon also reduced JAK2 allele burden — a disease-modifying effect anagrelide lacks — and was associated with fewer thrombotic events.
Key Limitations
Design: open-label — response assessment bias possible since ELN criteria include symptom components
Generalizability: 96% Asian population and a leukocytosis-selected phenotype limit applicability to broader/Western HU-refractory ET
Duration: median follow-up only 12.5 months — durability and transformation rates unknown; no head-to-head vs hydroxyurea in first-line ET
Generalizability: 96% Asian population and a leukocytosis-selected phenotype limit applicability to broader/Western HU-refractory ET
Duration: median follow-up only 12.5 months — durability and transformation rates unknown; no head-to-head vs hydroxyurea in first-line ET
Clinical Context
Ropeginterferon alfa-2b is FDA approved for polycythemia vera (PROUD-PV/CONTINUATION-PV). SURPASS-ET provides the first phase 3 evidence in ET, where it appears superior to anagrelide as second-line therapy; reduction in JAK2V617F allele burden differentiates it from cytoreductive agents like anagrelide. Ropeg may be preferred over anagrelide particularly in patients with leukocytosis, prior thrombosis, or when disease modification is desired. ESMO MPN guidance supports interferon-based therapy in high-risk ET.