Evaluation of an alternative ruxolitinib dosing regimen in patients with myelofibrosis: an open-label phase 2 study

Abstract Background Ruxolitinib improves splenomegaly and symptoms in patients with intermediate-2 or high-risk myelofibrosis; however, nearly half develop grade 3/4 anemia and/or thrombocytopenia, necessitating dose reductions and/or transfusions. We report findings from an open-label phase 2 study exploring a dose-escalation strategy aimed at preserving clinical benefit while reducing hematological adverse events early in ruxolitinib treatment. Methods Patients with myelofibrosis received ruxolitinib 10 mg twice daily (BID), with incremental increases of 5 mg BID at weeks 12 and 18 for lack of efficacy (maximum, 20 mg BID). Symptom severity was measured using the Myelofibrosis Symptom Assessment Form Total Symptom Score (MFSAF TSS). Results Forty-five patients were enrolled, 68.9% of whom had a Dynamic International Prognostic Scoring System score of 1 to 2 (i.e., intermediate-1 disease risk). Median percentage change in spleen volume from baseline to week 24 was − 17.3% (≥ 10% reduction achieved by 26 patients [57.8%]), with a clear dose response. Median percentage change in MFSAF TSS from baseline at week 24 was − 45.6%, also with a dose response. The most frequent treatment-emergent adverse events were anemia (26.7%), fatigue (22.2%), and arthralgias (20.0%). Grade 3/4 anemia (20.0%) and dose decreases due to anemia (11.1%) or thrombocytopenia (6.7%) were infrequent. Conclusions A dose-escalation approach may mitigate worsening anemia during early ruxolitinib therapy in some patients with myelofibrosis. Trial registration ClinicalTrials.gov identifier, NCT01445769 . Registered September 23, 2011.https://deepblue.lib.umich.edu/bitstream/2027.42/145195/1/13045_2018_Article_642.pd