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

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

Abstract

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 www.isrctn.com as #ISRCTN61925716.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Disease Progression
  • Drug Resistance*
  • Female
  • Hemorrhage / complications
  • Humans
  • Hydroxyurea / therapeutic use*
  • Male
  • Middle Aged
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Thrombocythemia, Essential / complications
  • Thrombocythemia, Essential / drug therapy*
  • Thrombocythemia, Essential / genetics
  • Thrombocythemia, Essential / pathology
  • Treatment Outcome
  • Withholding Treatment

Substances

  • INCB018424
  • Pyrazoles
  • Hydroxyurea

Associated data

  • ISRCTN/ISRCTN61925716