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Blood. 2017 Oct 26;130(17):1889-1897. doi: 10.1182/blood-2017-05-785790. Epub 2017 Aug 9.

Ruxolitinib vs best available therapy for ET intolerant or resistant to hydroxycarbamide.

Author information

Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
Weatherall Institute of Molecular Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.
Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom.
Heart of England NHS Foundation Trust, Birmingham, United Kingdom.
Colchester Hospital University NHS Foundation Trust, Colchester, United Kingdom.
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.
Department of Hematology, Cardiff University, Cardiff, United Kingdom.
Castle Hill Hospital, Hull, United Kingdom.
NIHR Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.
Department of Hematology and Oncology, Oregon Health and Sciences University, Portland, OR.
Mayo Clinic, Phoenix, AZ.
Division of Health Sciences Research, Mayo Clinic, Scottsdale, AZ.
Faculty of Medicine, University of Southampton, Southampton, United Kingdom; and.
Department of Hematology, Queen's University, Belfast, United Kingdom.


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 2 trial of ruxolitinib (JAK1/2 inhibitor) vs best available therapy (BAT) in ET and polycythemia vera patients resistant or intolerant to HC. Here, findings of MAJIC-ET are reported, where the modified intention-to-treat population included 58 and 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 2 complete molecular responses (CMR) and 1 partial molecular response in CALR-positive ruxolitinib-treated patients. Transformation to myelofibrosis occurred in 1 CMR patient, presumably because of the emergence of a different clone, raising questions about the relevance of CMR in ET patients. Grade 3 and 4 anemia occurred in 19% and 0% of ruxolitinib vs 0% (both grades) in the BAT arm, and grade 3 and 4 thrombocytopenia in 5.2% and 1.7% of ruxolitinib vs 0% (both grades) of BAT-treated patients. Rates of discontinuation or treatment switching did not differ between the 2 trial arms. The MAJIC-ET trial suggests that ruxolitinib is not superior to current second-line treatments for ET. This trial was registered at as #ISRCTN61925716.

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