TY - JOUR
T1 - A phase 2 study of ruxolitinib in combination with azacitidine in patients with myelofibrosis
AU - Masarova, Lucia
AU - Verstovsek, Srdan
AU - Hidalgo-Lopez, Juliana E.
AU - Pemmaraju, Naveen
AU - Bose, Prithviraj
AU - Estrov, Zeev
AU - Jabbour, Elias J.
AU - Ravandi-Kashani, Farhad
AU - Takahashi, Koichi
AU - Cortes, Jorge E.
AU - Ning, Jing
AU - Ohanian, Maro
AU - Alvarado, Yesid
AU - Zhou, Lingsha
AU - Pierce, Sherry
AU - Gergis, Romany
AU - Patel, Keyur P.
AU - Luthra, Rajyalakshmi
AU - Kadia, Tapan M.
AU - DiNardo, Courtney D.
AU - Borthakur, Gautam
AU - Bhalla, Kapil
AU - Garcia-Manero, Guillermo
AU - Bueso-Ramos, Carlos E.
AU - Kantarjian, Hagop M.
AU - Daver, Naval
N1 - Publisher Copyright:
© 2018 by The American Society of Hematology
PY - 2018/10/18
Y1 - 2018/10/18
N2 - Ruxolitinib (RUX)-based combinations may provide benefit for patients with myelofibrosis (MF). In this open-label, nonrandomized, prospective phase 2 study, patients with MF initially received RUX twice per day continuously in 28-day cycles for the first 3 cycles. Azacitidine (AZA) 25 mg/m2 (days 1-5) was added starting with cycle 4 and could be subsequently increased to 75 mg/m2 (days 1-5). Forty-six patients were enrolled with a median follow-up of 28 months (range, 4-501 months). An International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) response was achieved in 33 patients (72%), with a median time to response of 1.8 months (range, 0.7-19.0 months). One-fourth (7 of 33) of the IWG-MRT responses occurred after the addition of AZA. A reduction of >50% in palpable spleen length at 24 weeks and at any time on the study was achieved in 62% and 71% of the evaluable patients, respectively. Among patients who achieved a >50% reduction in spleen length at 24 weeks, 95% had maintained it at 48 weeks. Notably, improvements in bone marrow reticulin fibrosis grade occurred in 57% of the patients at 24 months. Treatment discontinuations as a result of drug-related toxicities occurred in 4 patients (9%), all as a result of cytopenias. New onset grade 3 to 4 anemia and thrombocytopenia occurred in 35% and 26% of patients, respectively. RUX and AZA were safe, with encouraging spleen response rates and improvement in bone marrow fibrosis in patients with MF. This trial was registered at www.clinicaltrials.gov as #NCT01787487.
AB - Ruxolitinib (RUX)-based combinations may provide benefit for patients with myelofibrosis (MF). In this open-label, nonrandomized, prospective phase 2 study, patients with MF initially received RUX twice per day continuously in 28-day cycles for the first 3 cycles. Azacitidine (AZA) 25 mg/m2 (days 1-5) was added starting with cycle 4 and could be subsequently increased to 75 mg/m2 (days 1-5). Forty-six patients were enrolled with a median follow-up of 28 months (range, 4-501 months). An International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) response was achieved in 33 patients (72%), with a median time to response of 1.8 months (range, 0.7-19.0 months). One-fourth (7 of 33) of the IWG-MRT responses occurred after the addition of AZA. A reduction of >50% in palpable spleen length at 24 weeks and at any time on the study was achieved in 62% and 71% of the evaluable patients, respectively. Among patients who achieved a >50% reduction in spleen length at 24 weeks, 95% had maintained it at 48 weeks. Notably, improvements in bone marrow reticulin fibrosis grade occurred in 57% of the patients at 24 months. Treatment discontinuations as a result of drug-related toxicities occurred in 4 patients (9%), all as a result of cytopenias. New onset grade 3 to 4 anemia and thrombocytopenia occurred in 35% and 26% of patients, respectively. RUX and AZA were safe, with encouraging spleen response rates and improvement in bone marrow fibrosis in patients with MF. This trial was registered at www.clinicaltrials.gov as #NCT01787487.
UR - http://www.scopus.com/inward/record.url?scp=85055209275&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055209275&partnerID=8YFLogxK
U2 - 10.1182/blood-2018-04-846626
DO - 10.1182/blood-2018-04-846626
M3 - Article
C2 - 30185431
AN - SCOPUS:85055209275
SN - 0006-4971
VL - 132
SP - 1664
EP - 1674
JO - Blood
JF - Blood
IS - 16
ER -