Dose escalation may combat worsening anemia during early ruxolitinib therapy in patients with myelofibrosis, according to a recent study published in the Journal of Hematology and Oncology. Ruxolitinib improves splenomegaly and alleviates the symptoms of intermediate-2 or high-risk myelofibrosis. However, its use is associated with an increased risk of developing grade 3/4 anemia and/or thrombocytopenia, requiring additional dose reductions or transfusions.

The authors of the study aimed to preserve clinical benefit, but reduce hematologic risk early during treatment using dose escalation. The study was an open-label phase 2 study of 45 patients with myelofibrosis, 68.9% of whom had a Dynamic International Prognostic Scoring System score of 1 to 2, indicating intermediate disease risk. Patients received ruxolitinib 10 mg twice daily with increases in increments of 5 mg at 12 weeks and 18 weeks for a maximum dose of 20 mg. Symptom severity was assessed using the Myelofibrosis Symptom Assessment Form Total Symptom Score.

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The median percentage change in spleen volume at 24 weeks from baseline was 17.3% with a clear dose response. Similarly, the median Myelofibrosis Symptom Assessment Form Total Symptom Score also showed a clear dose response and had a median percentage change of 45.6%. Incidence of grade 3/4 anemia (20%), dose decreases due to anemia (11.1%), or thrombocytopenia (6.7%) were uncommon. Other observed adverse effects were anemia (26.7%), fatigue (22.2%), and arthralgias (20%). According to the authors, “dose-escalation approach may mitigate worsening anemia during early ruxolitinib therapy in some patients with myelofibrosis.”

Reference

Talpaz M, Erickson-Viitanen S, Hou K, Hamburg S, Baer MR. Evaluation of an alternative ruxolitinib dosing regimen in patients with myelofibrosis: an open-label phase 2 study. J Hematol Oncol. 2018;11(1):101.