Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial
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Colleges, School and Institutes
- Weatherall Institute of Molecular Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.
- Cancer Research Clinical Trials Unit, School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom.
- Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
- Heart of England NHS Foundation Trust, 1727, Department of Diabetes and Endocrinology, Birmingham, Birmingham, United Kingdom of Great Britain and Northern Ireland.
- Centre for Clinical Hematology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
- Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom.
- Department of Hematology, London North West Healthcare NHS Trust, London, United Kingdom.
- Cardiff University
- NIHR Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.
- Department of Hematology and Oncology, Oregon Health and Sciences University, Portland, United States.
- Division of Health Sciences Research, Mayo Clinic, Scottsdale, AZ, United States.
- Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
- Mayo Clinic, Phoenix, AZ, United States.
- Department of Hematology, Queen's University, Belfast, United Kingdom.
- Colchester Hospital University NHS Foundation Trust
- Castle Hill Hospital, Hull and East Yorkshire Hospitals NHS Trust, Hull, UK.
Treatments for high-risk essential thrombocythemia (ET) address thrombocytosis, disease-related symptoms, as well as risks of thrombosis, hemorrhage, transformation to myelofibrosis and leukemia. Patients resistant/intolerant to hydroxycarbamide (HC) have a poor outlook. MAJIC (ISRCTN61925716) is a randomized phase II trial of ruxolitinib (JAK1/2 inhibitor) vs Best Available Therapy (BAT) in ET and polycythemia vera (PV) patients resistant or intolerant to HC. Here findings of MAJIC-ET are reported, where the modified intention-to-treat population included 58 & 52 patients randomized to receive ruxolitinib or BAT respectively. There was no evidence of improvement in complete response within 1 year reported in 27 (46.6%) patients treated with ruxolitinib vs 23 (44.2%) with BAT (P=.40). At 2 years rates of thrombosis, hemorrhage and transformation were not significantly different, however some disease-related symptoms improved in patients receiving ruxolitinib relative to BAT. Molecular responses were uncommon; there were two complete molecular responses (CMR) and one partial molecular response (PMR) in CALR positive ruxolitinib-treated patients. Transformation to myelofibrosis occurred in one CMR patient, presumably due to the emergence of a different clone raising questions about the relevance of CMR in ET patients. Grade 3&4 anemia occurred in 19% & 0% of ruxolitinib vs 0% (both grades) BAT arm, grade 3&4 thrombocytopenia in 5.2% & 1.7% of ruxolitinib vs 0% (both grades) of BAT treated patients. Rates of discontinuation or treatment switching did not differ between the two trial arms. The MAJIC-ET trial suggests that ruxolitinib is not superior to current second-line treatments for ET.
|Publication status||Published - 26 Oct 2017|