Azacitidine + ruxolitinib in MF: Phase II study results

Final results of an open-label, phase II study (NCT01787487) evaluating azacitidine (Aza) + ruxolitinib (Rux) in 61 patients with myelofibrosis (MF) were published in Haematologica by Arora et al. Patients were stratified into those with chronic phase MF (<10% blasts, n = 54) and accelerated phase MF (10–19% blasts, n = 7). The primary endpoint was objective response rate (ORR) per International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT), and the key secondary endpoint was safety.

Key data: In the chronic phase cohort, the ORR was 78%, including a spleen response and ≥50% reduction in total symptom score (TSS50) response in 66% and 68% of 41 evaluable patients, respectively, at any time on study. The median duration of response (DoR) of all responses was 33.1 months (95% confidence interval [CI], 19.1–46.7). At a median follow-up of 95.3 months, median overall survival (OS) was 56 months (95% CI, 38.2–99.3). In the accelerated phase cohort, the ORR was 43%, including a spleen response and TSS50 in 20% and 60% of patients, respectively. The median DoR for spleen and TSS50 responses were 29.4 months and 3.5 months, respectively. At a median follow-up of 38.3 months, the median OS was 30.8 months (95% CI, 9.2–34.1). All patients experienced ≥1 adverse event (AE); the most common Grade 3–5 treatment-emergent AEs (TEAEs) were anemia (54%), thrombocytopenia (39%), leukopenia/neutropenia (23%), pneumonia (15%), and hypertension (13%).

Key learning: In this study, Aza + Rux demonstrated robust, durable responses with no new safety signals in a high-risk MF cohort, supporting continued investigation of hypomethylating agent (HMA) + Janus kinase inhibitor (JAKi) combination strategies in MF.