Final results of a phase II study of the combination of azacitidine and ruxolitinib in patients with myelofibrosis

Abstract

Monotherapy with JAK2 inhibitors reduces splenomegaly and symptom burden but has limited effect on natural progression of myelofibrosis. We conducted a phase 2 clinical trial evaluating the combination of azacitidine (AZA) and ruxolitinib (RUX) in myelofibrosis. The interim analysis with 46 patients (median follow-up 28 months) demonstrated a response rate of 72%. We now report the final results of this clinical trial. The study primary endpoint was objective response rate by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria. From 3/2013 to 10/2021, 61 patients were treated (median age 66 years; range, 46-87 years). By baseline blast count, 54 patients had chronic phase disease (<10% blasts) and 7 had accelerated disease (10-19% blasts). In the chronic phase cohort, responses occurred in 42 patients (78%), including symptom and spleen response in 68% and 66% respectively. Leukemic transformation occurred in 4 patients (7%) on study, and 13 patients (24%) underwent allogeneic stem cell transplantation. After a median follow-up of 95.3 months, the median overall survival was 56 months (95% CI: 38.2-99.3). Among the 7 patients with accelerated disease, responses occurred in 3/7 (43%), and the median overall survival was 30.8 months (95% CI: 9.2-34.1). The most common grade 3-5 TEAEs were anemia (33, 54%), thrombocytopenia (24, 39%), leucopenia (14, 23%), and pneumonia (9, 15%). 4 patients (7%) discontinued study due to adverse events. The AZA-RUX combination demonstrated safety and efficacy in myelofibrosis, supporting further investigation of this regimen.