Final results of a phase II study of the combination of azacitidine and ruxolitinib in patients with myelofibrosis.
Key claim: Final phase II results show that combining azacitidine with ruxolitinib yields high objective response rates by IWG-MRT criteria in myelofibrosis, addressing the limited disease-modifying effect of JAK inhibitor monotherapy.
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 (.
Why this matters
JAK inhibitor monotherapy delivers spleen and symptom benefit in myelofibrosis but has limited disease-modifying activity, motivating combination strategies. Final phase II results for azacitidine + ruxolitinib provide durable efficacy data for a hypomethylating agent + JAKi backbone in PMF, joining pelabresib, selinexor, navitoclax, and pacritinib+HMA combinations as competing add-on paradigms. It also supports HMA-based approaches for accelerated/dysplastic PMF phenotypes where disease biology overlaps with MDS/MPN.