The Lancet. Haematology · 2025
Ropeginterferon alfa-2b in hydroxyurea-intolerant or hydroxyurea-refractory essential thrombocythaemia (SURPASS ET): a multicentre, open-label, randomised, active-controlled, phase 3 study.
СтатьяРандомизированное исследованиеКлиническое исследование III фазыМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Mesa Ruben, Gill Harinder, Zhang Lei, Jin Jie, Kirito Keita, Komatsu Norio, Qin Albert, Xiao Zhijian, Tashi Tsewang, Shimoda Kazuya, Ohishi Kohshi, Chen Suning, Zuo Xuelan, Shirane Shuichi, Hu Yu, Zhang Sujiang, Wang Yi, Takenaka Katsuto, Ichii Michiko, Xu Na, Shih Lee-Yung, Lim Ken-Hong, Lee Sung-Eun, Bae Sung Hwa, Teo Winnie Z Y, Maze Dawn, Oh Stephen T, Bose Prithviraj, Sato Toshiaki, Zagrijtschuk Oleh, Lin Sheena, Shih Weichung Joe, Mascarenhas John, Masarova Lucia, SURPASS-ET Study Group
Аннотация
BACKGROUND: The initial therapy for high-risk essential thrombocythaemia is usually hydroxyurea, but about a third of patients develop intolerance or resistance. A standard second-line agent has been anagrelide. Ropeginterferon alfa-2b, a new-generation interferon-based therapy, is approved for polycythaemia vera. We aimed to assess efficacy and safety of ropeginterferon alfa-2b compared with anagrelide in patients with essential thrombocythaemia with leukocytosis who are intolerant or resistant to hydroxyurea.
METHODS: The SURPASS ET open-label, randomised, active-controlled, phase 3 trial was done at 55 clinical sites across China, Japan, Taiwan, Hong Kong, South Korea, the USA, Singapore, and Canada and enrolled patients aged 18 years and older with high-risk (age >60 years with JAK2 Val617Phe or a history of disease-related thrombosis or haemorrhage), hydroxyurea-intolerant or hydroxyurea-resistant essential thrombocythaemia and white blood cell (WBC) count greater than 10 × 109 cells/L. Patients were randomly assigned (1:1) to ropeginterferon alfa-2b or anagrelide, stratified by platelet count, symptom score, and country. Ropeginterferon alfa-2b was subcutaneously dosed every 2 weeks, initially at 250 μg, then titrated to 350 μg at week 2, and to 500 μg from week 4 onward. Anagrelide was orally dosed according to the US Food and Drug Administration-approved prescribing information. The primary endpoint was the rate of response at months 9 and 12, as per modified European LeukemiaNet (ELN) criteria. The main planned analysis for the study was done in the intention-to-treat population. The trial is registered at ClinicalTrials.gov, NCT04285086 and is completed, and an extension study for collecting long-term data is ongoing.
FINDINGS: Between Aug 25, 2020, and Nov 12, 2024, 245 patients were screened and 174 were randomly assigned (91 to ropeginterferon alfa-2b and 83 to anagrelide). The median follow-up was 12·5 months (IQR 11·5-12·9). At baseline, 47 (52%) of 91 participants in the ropeginterferon alfa-2b group and 44 (53%) of 83 participants in the anagrelide group were female. 167 (96%) of 174 participants were Asian and seven (4%) were White. The trial met its primary endpoint, with 39 (43%) of 91 participants in the ropeginterferon alfa-2b group showing durable modified ELN criteria responses at months 9 and 12, compared with five (6%) of 83 participants in the anagrelide group. This difference (36·5%, 95% CI 25·4-47·7) was significant (p=0·0001). Grade 3 or worse treatment-emergent adverse events occurred in 27 (34%) of 80 patients in the anagrelide group and 21 (23%) of 91 patients in the ropeginterferon alfa-2b group. In the ropeginterferon alfa-2b group, the most common grade 3 or worse adverse events were infections and infestations, occurring eight (9%) of 91 patients, compared with five (6%) of 80 patients in the anagrelide group. In the anagrelide group, the most frequent grade 3 or worse adverse events were nervous system disorders, occurring in six (8%) of 80 patients, compared with one (1%) of 91 patients with ropeginterferon alfa-2b. Serious adverse events occurred in 24 (30%) of 80 participants in the anagrelide group and 13 (14%) of 91 participants in the ropeginterferon alfa-2b group). The most common serious adverse event was cerebral infarction, which occurred in four (5%) of 80 patients in the anagrelide group but was not observed in the ropeginterferon alfa-2b group. There were no treatment-related deaths in either study group.
INTERPRETATION: Our findings suggest that ropeginterferon alfa-2b could be considered as a second-line treatment option for patients with essential thrombocythaemia and leukocytosis.
FUNDING: PharmaEssentia.
METHODS: The SURPASS ET open-label, randomised, active-controlled, phase 3 trial was done at 55 clinical sites across China, Japan, Taiwan, Hong Kong, South Korea, the USA, Singapore, and Canada and enrolled patients aged 18 years and older with high-risk (age >60 years with JAK2 Val617Phe or a history of disease-related thrombosis or haemorrhage), hydroxyurea-intolerant or hydroxyurea-resistant essential thrombocythaemia and white blood cell (WBC) count greater than 10 × 109 cells/L. Patients were randomly assigned (1:1) to ropeginterferon alfa-2b or anagrelide, stratified by platelet count, symptom score, and country. Ropeginterferon alfa-2b was subcutaneously dosed every 2 weeks, initially at 250 μg, then titrated to 350 μg at week 2, and to 500 μg from week 4 onward. Anagrelide was orally dosed according to the US Food and Drug Administration-approved prescribing information. The primary endpoint was the rate of response at months 9 and 12, as per modified European LeukemiaNet (ELN) criteria. The main planned analysis for the study was done in the intention-to-treat population. The trial is registered at ClinicalTrials.gov, NCT04285086 and is completed, and an extension study for collecting long-term data is ongoing.
FINDINGS: Between Aug 25, 2020, and Nov 12, 2024, 245 patients were screened and 174 were randomly assigned (91 to ropeginterferon alfa-2b and 83 to anagrelide). The median follow-up was 12·5 months (IQR 11·5-12·9). At baseline, 47 (52%) of 91 participants in the ropeginterferon alfa-2b group and 44 (53%) of 83 participants in the anagrelide group were female. 167 (96%) of 174 participants were Asian and seven (4%) were White. The trial met its primary endpoint, with 39 (43%) of 91 participants in the ropeginterferon alfa-2b group showing durable modified ELN criteria responses at months 9 and 12, compared with five (6%) of 83 participants in the anagrelide group. This difference (36·5%, 95% CI 25·4-47·7) was significant (p=0·0001). Grade 3 or worse treatment-emergent adverse events occurred in 27 (34%) of 80 patients in the anagrelide group and 21 (23%) of 91 patients in the ropeginterferon alfa-2b group. In the ropeginterferon alfa-2b group, the most common grade 3 or worse adverse events were infections and infestations, occurring eight (9%) of 91 patients, compared with five (6%) of 80 patients in the anagrelide group. In the anagrelide group, the most frequent grade 3 or worse adverse events were nervous system disorders, occurring in six (8%) of 80 patients, compared with one (1%) of 91 patients with ropeginterferon alfa-2b. Serious adverse events occurred in 24 (30%) of 80 participants in the anagrelide group and 13 (14%) of 91 participants in the ropeginterferon alfa-2b group). The most common serious adverse event was cerebral infarction, which occurred in four (5%) of 80 patients in the anagrelide group but was not observed in the ropeginterferon alfa-2b group. There were no treatment-related deaths in either study group.
INTERPRETATION: Our findings suggest that ropeginterferon alfa-2b could be considered as a second-line treatment option for patients with essential thrombocythaemia and leukocytosis.
FUNDING: PharmaEssentia.