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

Lucia Masarova, Srdan Verstovsek, Juliana E. Hidalgo-Lopez, Naveen Pemmaraju, Prithviraj Bose, Zeev Estrov, Elias J. Jabbour, Farhad Ravandi-Kashani, Koichi Takahashi, Jorge E. Cortes, Jing Ning, Maro Ohanian, Yesid Alvarado, Lingsha Zhou, Sherry Pierce, Romany Gergis, Keyur P. Patel, Rajyalakshmi Luthra, Tapan M. Kadia, Courtney D. DiNardo, Gautam Borthakur, Kapil Bhalla, Guillermo Garcia-Manero, Carlos E. Bueso-Ramos, Hagop M. Kantarjian and Naval Daver

Key Points

  • The combination of RUX and AZA was safe with encouraging spleen response rates at 24 weeks and any time on study.

  • RUX and AZA demonstrated marked improvements in bone marrow fibrosis at 24 months when compared with RUX alone.


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 as #NCT01787487.

  • Submitted April 20, 2018.
  • Accepted August 27, 2018.
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