The combination of ruxolitinib and azacitidine appears to be safe in encouraging spleen response rates in patients with myelofibrosis, according to results from an open-label, non-randomized, prospective phase 2 study published in Blood. Researchers reported that ruxolitinib plus azacitidine also demonstrated improvements in bone marrow fibrosis when compared with ruxolitinib alone.

In this study, patients initially received ruxolitinib continuously, twice daily, in 28-day cycles. After 3 cycles, patients received 25 mg/m2 azacitidine during days 1-5 of each cycle. The dosage of azacitidine could be subsequently increased to 75 mg/m2. The trial included 46 patients and the median follow-up was 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. The study showed that 7 of the IWG-MRT responses occurred after the addition of azacitidine. There was a greater than 50% reduction in palpable spleen length at 24 weeks in 62% of the evaluable patients. Among patients who achieved a greater than 50% reduction in spleen length at 24 weeks, 95% were able to maintain this status at 48 weeks. Additionally, the researchers found that 57% of the patients experienced improvements in bone marrow reticulin fibrosis grade at 24 months. Treatment-related discontinuation rates in this study were similar to those seen in patients receiving single-agent ruxolitinib.

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Azacitidine is approved by the US Food and Drug Administration for patients with myelodysplastic syndrome and is commonly employed for treating older patients with newly diagnosed acute myeloid leukemia. The researchers reported that the combination of the 2 drugs appears to have a synergistic effect. However, they cautioned that these findings “must be weighed against a higher incidence of early and late (> 48 weeks) cytopenias” and indicated that longer follow-up and randomized trials are warranted.

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1. Masarova L, Verstovsek S, Hidalgo-Lopez JE, et al. A phase II study of ruxolitinib in combination with azacytidine in patients with myelofibrosis [published online October 18, 2018]. Blood. doi: 10.1182/blood-2018-04-846626