Ruxolitinib for myelofibrosis-An update of its clinical effects

Hagop M. Kantarjian, Richard T. Silver, Rami S. Komrokji, Ruben A. Mesa, Roland Tacke, Claire N. Harrison

Research output: Contribution to journalReview articlepeer-review

17 Scopus citations

Abstract

Myelofibrosis (MF), a Philadelphia chromosome-negative myeloproliferative neoplasm, is characterized by progressive bone marrow fibrosis and ineffective hematopoiesis. Clinical hallmarks include splenomegaly, anemia, and debilitating symptoms. In 2 randomized phase III studies, the Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib significantly improved splenomegaly and disease-related symptoms compared with placebo (Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment [COMFORT-I]) or best available therapy (COMFORT-II) in patients with intermediate-2 or high-risk MF. Although ruxolitinib therapy was associated with dose-dependent anemia and thrombocytopenia, these adverse events rarely led to treatment discontinuation. This update of the clinical effects of ruxolitinib in patients with MF was based on original articles and meeting abstracts published after the primary publication of the COMFORT trials in March 2012. Long-term follow-up data from the COMFORT trials and clinical experience with ruxolitinib in unselected patient populations suggest that improvement of splenomegaly and symptoms is durable. Patients benefit from ruxolitinib therapy across subgroups defined by age, MF type, risk category, performance status, JAK2 V617F mutation status, extent of splenomegaly, or presence of cytopenias. In COMFORT-I, platelet counts stabilized with dose adjustments, and hemoglobin levels gradually recovered to slightly below baseline after the first 8 to 12 weeks of therapy. After initial increases, the need for red blood cell transfusions decreased to a level similar to that found in the placebo group. The 2-year follow-up data from the COMFORT trials suggest that patients with intermediate-2 or high-risk MF receiving ruxolitinib therapy may have improved survival compared with those receiving no (placebo) or traditional therapy.

Original languageEnglish (US)
Pages (from-to)638-645
Number of pages8
JournalClinical Lymphoma, Myeloma and Leukemia
Volume13
Issue number6
DOIs
StatePublished - Dec 2013

Keywords

  • JAK inhibitor
  • Myeloproliferative neoplasm
  • Overall survival
  • Ruxolitinib
  • Splenomegaly

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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