Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis

A. Pardanani, R. R. Laborde, T. L. Lasho, C. Finke, K. Begna, A. Al-Kali, W. J. Hogan, M. R. Litzow, A. Leontovich, M. Kowalski, A. Tefferi

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168 Scopus citations


JAK-STAT is a rational drug target in myelofibrosis (MF) given its association with JAK2/MPL mutations and aberrant inflammatory cytokine expression. We conducted a Phase 1/2 trial of CYT387, a potent JAK1/2 inhibitor, in patients with high- or intermediate-risk primary or post-polycythemia vera/essential thrombocythemia MF. Pre-planned safety and efficacy analysis has been completed for the initial 60 patients. In the dose-escalation phase (n=21), the maximum-tolerated dose was 300 mg/day based on reversible grade 3 headache and asymptomatic hyperlipasemia. Twenty-one and 18 additional patients were accrued at two biologically effective doses, 300 mg/day and 150 mg/day, respectively. Anemia and spleen responses, per International Working Group criteria, were 59% and 48%, respectively. Among 33 patients who were red cell-transfused in the month prior to study entry, 70% achieved a minimum 12-week period without transfusions (range 4.7->18.3 months). Most patients experienced constitutional symptoms improvement. Grade 3/4 adverse reactions included thrombocytopenia (32%), hyperlipasemia (5%), elevated liver transaminases (3%) and headache (3%). New-onset treatment-related peripheral neuropathy was observed in 22% of patients (sensory symptoms, grade 1). CYT387 is well tolerated and produces significant anemia, spleen and symptom responses in MF patients. Plasma cytokine and gene expression studies suggested a broad anticytokine drug effect.

Original languageEnglish (US)
Pages (from-to)1322-1327
Number of pages6
Issue number6
StatePublished - Jun 2013


  • JAK2V617F
  • myeloproliferative
  • polycythemia
  • thrombocythemia

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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