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

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.

• Authors: 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, Naval Daver
• Journal: Blood (Blood) Vol. 132 Issue 16 Pg. 1664-1674 (10 18 2018) ISSN: 1528-0020 [Electronic] United States
• PMID: 30185431 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 by The American Society of Hematology.

Chemical References

• Nitriles
• Pyrazoles
• Pyrimidines
• ruxolitinib
• Azacitidine

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Azacitidine (administration & dosage)
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Nitriles
• Primary Myelofibrosis (drug therapy, pathology)
• Prognosis
• Prospective Studies
• Pyrazoles (administration & dosage)
• Pyrimidines
• Safety
• Survival Rate