Fedratinib in patients with myelofibrosis previously treated with ruxolitinib: An updated analysis of the JAKARTA2 study using stringent criteria for ruxolitinib failure

C.N. Harrison*, N. Schaap, A.M. Vannucchi, J.J. Kiladjian, E. Jourdan, R.T. Silver, H.C. Schouten, F. Passamonti, S. Zweegman, M. Talpaz, S. Verstovsek, S. Rose, J. Shen, T. Berry, C. Brownstein, R.A. Mesa

*Corresponding author for this work

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Abstract

Fedratinib is an oral, selective Janus kinase 2 (JAK2) inhibitor. The phase II JAKARTA2 study assessed fedratinib in patients with intermediate- or high-risk myelofibrosis (MF) who were resistant or intolerant to prior ruxolitinib per investigator assessment. Patients received fedratinib 400 mg/day in 28-day cycles. The JAKARTA2 outcomes were initially reported using a last-observation-carried forward (LOCF) analysis in a "Per Protocol" population. This updated analysis of JAKARTA2 employs intention-to-treat analysis principles without LOCF for all treated patients (ITT Population; N = 97), and for a patient subgroup who met more stringent definitions of prior ruxolitinib failure (Stringent Criteria Cohort; n = 79). Median duration of prior ruxolitinib exposure was 10.7 months. The primary endpoint was spleen volume response rate (SVRR; >= 35% spleen volume decrease from baseline to end of cycle 6 [EOC6]). The SVRR was 31% in the ITT Population and 30% in the Stringent Criteria Cohort. Median duration of spleen volume response was not reached. Symptom response rate (>= 50% reduction from baseline to EOC6 in total symptom score [TSS] on the modified Myelofibrosis Symptom Assessment Form [MFSAF]) was 27%. Grade 3-4 anemia and thrombocytopenia rates were 38% and 22%, respectively. Patients with advanced MF substantially pretreated with ruxolitinib attained robust spleen responses and reduced symptom burden with fedratinib.
Original languageEnglish
Pages (from-to)594-603
Number of pages10
JournalAmerican Journal of Hematology
Volume95
Issue number6
DOIs
Publication statusPublished - 1 Jun 2020

Keywords

  • available therapy
  • double-blind
  • efficacy
  • encephalopathy
  • inhibitor fedratinib
  • open-label
  • outcomes
  • phase-3
  • safety
  • sar302503
  • EFFICACY
  • SAFETY
  • OPEN-LABEL
  • PHASE-3
  • ENCEPHALOPATHY
  • DOUBLE-BLIND
  • SAR302503
  • OUTCOMES
  • INHIBITOR FEDRATINIB
  • AVAILABLE THERAPY

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