Efficacy and safety of a novel dosing strategy for ruxolitinib in the treatment of patients with myelofibrosis and anemia: the REALISE phase 2 study.

Anemia is a frequent manifestation of myelofibrosis (MF) and there is an unmet need for effective treatments in anemic MF patients. The REALISE phase 2 study (NCT02966353) evaluated the efficacy and safety of a novel ruxolitinib dosing strategy with a reduced starting dose with delayed up-titration in anemic MF patients. Fifty-one patients with primary MF (66.7%), post-essential thrombocythemia MF (21.6%), or post-polycythemia vera MF (11.8%) with palpable splenomegaly and hemoglobin <10 g/dl were included. Median age was 67 (45-88) years, 41.2% were female, and 18% were transfusion-dependent. Patients received 10 mg ruxolitinib b.i.d. for the first 12 weeks, then up-titrations of up to 25 mg b.i.d. were permitted, based on efficacy and platelet counts. Overall, 70% of patients achieved a ≥50% reduction in palpable spleen length at any time during the study. The most frequent adverse events leading to dose interruption/adjustment were thrombocytopenia (17.6%) and anemia (11.8%). Patients who had a dose increase had greater spleen size and higher white blood cell counts at baseline. Median hemoglobin levels remained stable and transfusion requirements did not increase compared with baseline. These results reinforce the notion that it is unnecessary to delay or withhold ruxolitinib because of co-existent or treatment-emergent anemia.