Ruxolitinib versus best available therapy for ET intolerant or resistant to hydroxycarbamide in a randomized trial

Research output: Contribution to journalArticlepeer-review


  • Claire N Harrison
  • Adam J Mead
  • Sonia Fox
  • Emmanouela Gbandi
  • Samah Alimam
  • Joanne Ewing
  • Marion Wood
  • Frederick Chen
  • Jason Coppell
  • Nicki Panoskaltsis
  • Steven Knapper
  • Sahra Ali
  • Angela Hamblin
  • Ruben Scherber
  • Amylou C Dueck
  • Nicholas C P Cross
  • Ruben Mesa
  • Mary Frances McMullin

Colleges, School and Institutes

External organisations

  • University of Oxford
  • 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.
  • University Hospitals Birmingham NHS Foundation Trust
  • Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom.
  • Department of Hematology, London North West Healthcare NHS Trust, London, United Kingdom.
  • Cardiff University
  • Department of Hematology and Oncology, Oregon Health and Sciences University, Portland, United States.
  • Division of Health Sciences Research, Mayo Clinic, Scottsdale, AZ, United States.
  • University of Southampton
  • 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.


Original languageEnglish
Pages (from-to)1889-1897
Issue number17
Publication statusPublished - 26 Oct 2017