TY - JOUR
T1 - Long-term effects of ruxolitinib versus best available therapy on bone marrow fibrosis in patients with myelofibrosis
AU - Kvasnicka, Hans Michael
AU - Thiele, Jürgen
AU - Bueso-Ramos, Carlos E.
AU - Sun, William
AU - Cortes, Jorge
AU - Kantarjian, Hagop M.
AU - Verstovsek, Srdan
N1 - Funding Information:
H.M.K. reports receiving consulting or advisory fees from Incyte Corporation, AOP Orphan Pharmaceuticals, and Novartis; honoraria from Incyte Corporation and Novartis; research funding from AOP Orphan Pharmaceuticals and Novartis; and other remunerations from Incyte Corporation and Novartis. J.T. reports receiving consulting or advisory fees from Incyte Corporation, AOP Orphan Pharmaceuticals, Novartis, and Sanofi; honoraria from Incyte Corporation, Novartis, and Sanofi; research funding from Incyte Corporation, AOP Orphan Pharmaceuticals, Novartis, and Shire; and other remunerations from Incyte Corporation, Novartis, and Sanofi. C.E.B-R reports receiving consulting or advisory fees from Incyte Corporation and honoraria from Novartis. W.S. is an employee of and holds stock in Incyte Corporation. J.C. reports receiving consulting or advisory fees from Incyte Corporation and Sanofi and receiving research funding from Incyte Corporation and Sanofi. H.M.K. reports receiving research funding from ARIAD, Bristol-Myers Squibb, Novartis, and Pfizer. S.V. reports receiving research funding from Incyte Corporation, AstraZeneca, Lilly Oncology, Geron, NS Pharma, Bristol-Myers Squibb, Novartis, Celgene, Gilead, Seattle Genetics, Promedior, and Cell Therapeutics, Inc.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/3/15
Y1 - 2018/3/15
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.
AB - 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.
KW - Bone marrow fibrosis
KW - Hydroxyurea
KW - Myelofibrosis
KW - Ruxolitinib
UR - http://www.scopus.com/inward/record.url?scp=85043754458&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85043754458&partnerID=8YFLogxK
U2 - 10.1186/s13045-018-0585-5
DO - 10.1186/s13045-018-0585-5
M3 - Article
C2 - 29544547
AN - SCOPUS:85043754458
SN - 1756-8722
VL - 11
JO - Journal of Hematology and Oncology
JF - Journal of Hematology and Oncology
IS - 1
M1 - 42
ER -