Universität zu Köln

Kvasnicka, Hans Michael, Thiele, Juergen, Bueso-Ramos, Carlos E., Sun, William, Cortes, Jorge ORCID: 0000-0002-8636-1071, Kantarjian, Hagop M. and Verstovsek, Srdan (2018). Long-term effects of ruxolitinib versus best available therapy on bone marrow fibrosis in patients with myelofibrosis. J. Hematol. Oncol., 11. LONDON: BMC. ISSN 1756-8722

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kvasnicka, Hans Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Bueso-Ramos, Carlos E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sun, William UNSPECIFIED UNSPECIFIED UNSPECIFIED Cortes, Jorge UNSPECIFIED orcid.org/0000-0002-8636-1071 UNSPECIFIED Kantarjian, Hagop M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Verstovsek, Srdan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-192670
DOI:	10.1186/s13045-018-0585-5
Journal or Publication Title:	J. Hematol. Oncol.
Volume:	11
Date:	2018
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1756-8722
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHRONIC IDIOPATHIC MYELOFIBROSIS; INTERNATIONAL WORKING GROUP; PROGNOSTIC SCORING SYSTEM; ESSENTIAL THROMBOCYTHEMIA; EUROPEAN CONSENSUS; POLYCYTHEMIA-VERA; DOUBLE-BLIND; COMFORT-II; FOLLOW-UP; SURVIVAL Multiple languages Oncology; Hematology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19267