TY  - JOUR
A1  - Kvasnicka, Hans Michael
A1  - Thiele, Jürgen
A1  - Bueso-Ramos, Carlos E.
A1  - Sun, William
A1  - Cortes, Jorge
A1  - Kantarjian, Hagop
A1  - Verstovsek, Srdan
T1  - Long-term effects of ruxolitinib versus best available therapy on bone marrow fibrosis in patients with myelofibrosis
T2  - Journal of hematology & oncology
N2  - 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.
KW  - Bone marrow fibrosis
KW  - Myelofibrosis
KW  - Ruxolitinib
KW  - Hydroxyurea
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/53417
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-534178
SN  - 1756-8722
N1  - Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
VL  - 11
IS  - 1, Art. 42
SP  - 1
EP  - 10
PB  - Biomed Central
CY  - London
ER  -