Abstract
Essential thrombocythaemia (ET) is a rare myeloproliferative neoplasm. This multicentre, Phase 3b, randomised, open-label, non-inferiority study investigated the cardiac safety, efficacy and tolerability of first-line treatment with anagrelide or hydroxyurea in high-risk ET patients for up to 3 years. Eligible patients aged ≥ 18 years with a diagnosis of high-risk ET confirmed by bone marrow biopsy within 6 months of randomisation received anagrelide (n = 75) or hydroxyurea (n = 74), administered twice daily. Treatment dose for either compound was titrated to the lowest dose needed to achieve a response. Planned primary outcome measures were change in left ventricular ejection fraction from baseline over time and platelet count at Month 6. Planned secondary outcome measures were platelet count change from baseline at Months 3 and 36; percentage of patients with complete or partial response; time to complete or partial response; number of patients with thrombohaemorrhagic events; and changes in white blood cell count or red blood cell count over time. Neither treatment altered cardiac function. There were no significant differences in adverse events between treatment groups, and no reports of malignant transformation. The incidence of disease-related thrombotic or haemorrhagic events was numerically higher in anagrelide-treated patients. Both treatments controlled platelet counts at 6 months, with the majority of patients experiencing complete or partial responses. In conclusion, these results suggest that long-term treatment with anagrelide is not associated with adverse effects on cardiac function. This is one of the few studies using left ventricular ejection fraction assessment and central biopsy reading to confirm the diagnosis of ET.Trial registration number: Clinicaltrials.gov NCT00202644
Highlights
Essential thrombocythaemia (ET) is a rare myeloproliferative neoplasm characterised by elevated platelet counts, megakaryocyte hyperplasia and enlargement, and one of the following: JAK2, CALR or MPL mutations, a clonal marker, or lack of evidence for reactive thrombocytosis [1, 2]
This study suggests that first-line long-term treatment with anagrelide is not associated with significant changes in cardiac function in patients with high-risk ET
Given concerns that phosphodiesterase 3 (PDE3) inhibition with anagrelide and resulting positive inotropic and chronotropic effects could lead to adverse changes in cardiac function, the lack of significant impact on left ventricular ejection fraction (LVEF) with long-term use in this study is an important observation, enhancing understanding of the safety profile of anagrelide
Summary
Essential thrombocythaemia (ET) is a rare myeloproliferative neoplasm characterised by elevated platelet counts, megakaryocyte hyperplasia and enlargement, and one of the following: JAK2, CALR or MPL mutations, a clonal marker, or lack of evidence for reactive thrombocytosis [1, 2]. In. Cardiovascular Toxicology (2021) 21:236–247 the European Union, incidence of ET ranges from 0.38 to 1.7 per 100,000 per year [3], with patients aged ≥ 60 years or with history of thrombosis at elevated risk of poor outcomes [2]. For patients with low-risk ET, treatment guidelines recommend observation or low-dose aspirin [8,9,10]. Firstline treatment for high-risk ET includes low-dose aspirin plus cytoreductive therapy; given the evidence for reduced thrombotic complications with platelet-lowering agents, the optimal choice of treatment between hydroxyurea, anagrelide (Xagrid®) and interferon-α is unclear [2]. In 2018, European LeukemiaNet recommended anagrelide as a second-line therapy after hydroxyurea [8]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
