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: Catriona Jamieson, Robert Hasserjian, Jason Gotlib, Jorge Cortes, Richard Stone, Moshe Talpaz, Jürgen Thiele, Scott Rodig, Olga Pozdnyakova
• Journal: Journal of translational medicine (J Transl Med) Vol. 13 Pg. 294 (Sep 10 2015) ISSN: 1479-5876 [Electronic] England
• PMID: 26357842 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Pyrrolidines
• Sulfonamides
• fedratinib
• JAK2 protein, human
• Janus Kinase 2

Topics

• Aged
• Biopsy
• Bone Marrow (drug effects)
• Bone Marrow Cells (cytology)
• Female
• Fibrosis (drug therapy, metabolism)
• Humans
• Janus Kinase 2 (antagonists & inhibitors, chemistry)
• Male
• Middle Aged
• Myeloproliferative Disorders (drug therapy, metabolism)
• Primary Myelofibrosis (drug therapy, metabolism)
• Prognosis
• Pyrrolidines (therapeutic use)
• Sulfonamides (therapeutic use)
• Treatment Outcome