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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2018

Open Access 01-12-2018 | Research

Long-term effects of ruxolitinib versus best available therapy on bone marrow fibrosis in patients with myelofibrosis

Authors: Hans Michael Kvasnicka, Jürgen Thiele, Carlos E. Bueso-Ramos, William Sun, Jorge Cortes, Hagop M. Kantarjian, Srdan Verstovsek

Published in: Journal of Hematology & Oncology | Issue 1/2018

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Abstract

Background

Myelofibrosis (MF) is a life-shortening complication of myeloproliferative neoplasms associated with ineffective hematopoiesis, splenomegaly, and progressive bone marrow (BM) fibrosis. The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib has been shown to improve splenomegaly, symptom burden, and overall survival in patients with intermediate-2 or high-risk MF compared with placebo or best available therapy (BAT).

Methods

The effects of ruxolitinib therapy for up to 66 months on BM morphology in 68 patients with advanced MF with variable BM fibrosis grade were compared with those in 192 matching patients treated with BAT. Available trephine biopsies underwent independent, blinded review by three hematopathologists for consensus-based adjudication of grades for reticulin fibrosis, collagen deposition, and osteosclerosis.

Results

Ruxolitinib treatment versus BAT was associated with greater odds of BM fibrosis improvement or stabilization and decreased odds of BM fibrosis worsening based on changes from baseline in reticulin fibrosis grade. Generally, these changes were accompanied by a sustained higher level of individual spleen size reduction and regression of leukoerythroblastosis. Patients with more advanced baseline fibrosis showed lower spleen size response.

Conclusions

The finding that long-term ruxolitinib therapy may reverse or markedly delay BM fibrosis progression in advanced MF suggests that sustained JAK inhibition may be disease-modifying.

Trial registration

INCB18424-251, ClinicalTrials.gov identifier NCT00509899.
Appendix
Available only for authorised users
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Metadata
Title
Long-term effects of ruxolitinib versus best available therapy on bone marrow fibrosis in patients with myelofibrosis
Authors
Hans Michael Kvasnicka
Jürgen Thiele
Carlos E. Bueso-Ramos
William Sun
Jorge Cortes
Hagop M. Kantarjian
Srdan Verstovsek
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2018
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-018-0585-5

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