A phase 2 study of ruxolitinib in combination with azacitidine in patients with myelofibrosis.

Autor:	Masarova L; Department of Leukemia., Verstovsek S; Department of Leukemia., Hidalgo-Lopez JE; Department of Hematopathology, and., Pemmaraju N; Department of Leukemia., Bose P; Department of Leukemia., Estrov Z; Department of Leukemia., Jabbour EJ; Department of Leukemia., Ravandi-Kashani F; Department of Leukemia., Takahashi K; Department of Leukemia., Cortes JE; Department of Leukemia., Ning J; Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX., Ohanian M; Department of Leukemia., Alvarado Y; Department of Leukemia., Zhou L; Department of Leukemia., Pierce S; Department of Leukemia., Gergis R; Department of Leukemia., Patel KP; Department of Hematopathology, and., Luthra R; Department of Hematopathology, and., Kadia TM; Department of Leukemia., DiNardo CD; Department of Leukemia., Borthakur G; Department of Leukemia., Bhalla K; Department of Leukemia., Garcia-Manero G; Department of Leukemia., Bueso-Ramos CE; Department of Hematopathology, and., Kantarjian HM; Department of Leukemia., Daver N; Department of Leukemia.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2018 Oct 18; Vol. 132 (16), pp. 1664-1674. Date of Electronic Publication: 2018 Sep 05.
DOI:	10.1182/blood-2018-04-846626
Abstrakt:	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/m 2 (days 1-5) was added starting with cycle 4 and could be subsequently increased to 75 mg/m 2 (days 1-5). Forty-six patients were enrolled with a median follow-up of 28 months (range, 4-50+ 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. (© 2018 by The American Society of Hematology.)
Databáze:	MEDLINE
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