Evaluation of an alternative ruxolitinib dosing regimen in patients with myelofibrosis: an open-label phase 2 study

J Hematol Oncol. 2018 Aug 7;11(1):101. doi: 10.1186/s13045-018-0642-0.


Background: Ruxolitinib improves splenomegaly and symptoms in patients with intermediate-2 or high-risk myelofibrosis; however, nearly half develop grade 3/4 anemia and/or thrombocytopenia, necessitating dose reductions and/or transfusions. We report findings from an open-label phase 2 study exploring a dose-escalation strategy aimed at preserving clinical benefit while reducing hematological adverse events early in ruxolitinib treatment.

Methods: Patients with myelofibrosis received ruxolitinib 10 mg twice daily (BID), with incremental increases of 5 mg BID at weeks 12 and 18 for lack of efficacy (maximum, 20 mg BID). Symptom severity was measured using the Myelofibrosis Symptom Assessment Form Total Symptom Score (MFSAF TSS).

Results: Forty-five patients were enrolled, 68.9% of whom had a Dynamic International Prognostic Scoring System score of 1 to 2 (i.e., intermediate-1 disease risk). Median percentage change in spleen volume from baseline to week 24 was - 17.3% (≥ 10% reduction achieved by 26 patients [57.8%]), with a clear dose response. Median percentage change in MFSAF TSS from baseline at week 24 was - 45.6%, also with a dose response. The most frequent treatment-emergent adverse events were anemia (26.7%), fatigue (22.2%), and arthralgias (20.0%). Grade 3/4 anemia (20.0%) and dose decreases due to anemia (11.1%) or thrombocytopenia (6.7%) were infrequent.

Conclusions: A dose-escalation approach may mitigate worsening anemia during early ruxolitinib therapy in some patients with myelofibrosis.

Trial registration: ClinicalTrials.gov identifier, NCT01445769 . Registered September 23, 2011.

Keywords: Anemia; Janus kinase; Myelofibrosis; Ruxolitinib; Thrombocytopenia; Transfusion.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Janus Kinases / pharmacology
  • Janus Kinases / therapeutic use*
  • Male
  • Middle Aged
  • Primary Myelofibrosis / drug therapy*
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use*


  • INCB018424
  • Pyrazoles
  • Janus Kinases

Associated data

  • ClinicalTrials.gov/NCT01445769