title: Effect of treatment with a JAK2-selective inhibitor, fedratinib, on bone marrow fibrosis in patients with myelofibrosis.
abstract: BACKGROUND
  Progressive bone marrow fibrosis (BMF) is a cardinal feature of many myeloproliferative neoplasms (MPNs) and there is a documented association between the severity of BMF and overall prognosis. We conducted an exploratory analysis of sequential BMF data from two phase I studies of long-term treatment with the Janus kinase 2 (JAK2) inhibitor fedratinib in patients with myelofibrosis.
  
  
  METHODS
  Bone marrow samples were obtained at baseline and after every six cycles (24 weeks) of daily fedratinib treatment. Fibrosis was centrally assessed by three independent haematopathologists, who were blinded to the patients' data, and graded according to European Consensus Myelofibrosis Grading Criteria. The analysis population comprised patients with a baseline BMF grade ≥1, and at least one post-baseline BMF grade assessment. Changes in BMF grade compared with baseline were classified as improvement (≥1 grade reduction), stabilisation (no change in any baseline BMF grade <3) or worsening (≥1 grade increase).
  
  
  RESULTS
  Twenty-one patients were included in the analysis. A total of 153 bone marrow samples were analysed. Improvement or stabilisation of BMF from baseline was recorded in 15 of 18 (83%) evaluable patients at cycle 6 and in four of nine (44%) evaluable patients at cycle 30. Two patients achieved resolution of their BMF (grade = 0) by cycle 12.
  
  
  CONCLUSIONS
  This exploratory analysis indicates that improvement or even resolution of BMF may be achievable with JAK2 inhibitor therapy in some patients with MPNs and myelofibrosis.
authors.affiliation: Moores UC San Diego Cancer Centre, 3855 Health Sciences Drive, La Jolla, CA, 92093-0820, USA. cjamieson@ucsd.edu.
authors.forename: Catriona
authors.initials: C
authors.lastname: Jamieson
authors.affiliation: Department of Pathology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA. RHASSERJIAN@mgh.harvard.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Hasserjian
authors.affiliation: Division of Hematology, Stanford University School of Medicine/Stanford Cancer Institute, 875 Blake Wilbur Drive, Room 2324, Stanford, CA, 94305, USA. gotlib@stanford.edu.
authors.forename: Jason
authors.initials: J
authors.lastname: Gotlib
authors.affiliation: Division of Cancer Medicine, Department of Leukemia, University of Texas MD Anderson Cancer Center, Faculty Center Building on Floors 3 and 4, 1515 Holcombe Blvd., Houston, TX, 77030, USA. jcortes@mdanderson.org.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.affiliation: Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA. Richard_Stone@dfci.harvard.edu.
authors.forename: Richard
authors.initials: R
authors.lastname: Stone
authors.affiliation: The University of Michigan Hospital and Health Systems, Comprehensive Cancer Center, 1500 East Medical Center Drive, Ann Arbor, MI, 48109, USA. mtalpaz@med.umich.edu.
authors.forename: Moshe
authors.initials: M
authors.lastname: Talpaz
authors.affiliation: Institute of Pathology, University of Cologne, Kerpener Str. 62, 50924, Cologne, Germany. j.thiele@uni-koeln.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Thiele
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. SRODIG@PARTNERS.ORG.
authors.forename: Scott
authors.initials: S
authors.lastname: Rodig
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. OPOZDNYAKOVA@PARTNERS.ORG.
authors.forename: Olga
authors.initials: O
authors.lastname: Pozdnyakova
mesh_terms: D000368:Aged; D001706:Biopsy; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology*; D005260:Female; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000188:drug therapy / Q000378:metabolism; D055728:Primary Myelofibrosis / Q000188:drug therapy / Q000378:metabolism*; D011379:Prognosis; D011759:Pyrrolidines / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D000096926:Benzenesulfonamides
chemical_list: D053614:Janus Kinase 2; D011759:Pyrrolidines; D013449:Sulfonamides; C528327:fedratinib; D000096926:Benzenesulfonamides; C507924:JAK2 protein, human