A phase 2 study of ruxolitinib in combination with azacitidine in patients with myelofibrosis BLOOD Masarova, L., Verstovsek, S., Hidalgo-Lopez, J. E., Pemmaraju, N., Bose, P., Estrov, Z., Jabbour, E. J., Ravandi-Kashani, F., Takahashi, K., Cortes, J. E., Ning, J., Ohanian, M., Alvarado, Y., Zhou, L., Pierce, S., Gergis, R., Patel, K. P., Luthra, R., Kadia, T. M., DiNardo, C. D., Borthakur, G., Bhalla, K., Garcia-Manero, G., Bueso-Ramos, C. E., Kantarjian, H. M., Daver, N. 2018; 132 (16): 1664–74

Abstract

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, 4-50+ 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.

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