Using a dose-escalation approach with ruxolitinib may lessen the occurrence and severity of anemia in patients with myelofibrosis (MF), according to a study published in the Journal of Hematology & Oncology.
Ruxolitinib improves splenomegaly and symptoms among patients with intermediate- to high-risk MF — a subtype of myeloproliferative neoplasms — but has been associated with high-rates of hematologic adverse events (AEs) such as anemia and thrombocytopenia. A dose-escalation strategy may sustain these benefits while reducing the toxicity of ruxolitinib.
For this phase 2 study, researchers enrolled 45 patients with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF. Patients received ruxolitinib 10 mg twice daily, and had gradual 5 mg increases up to a maximum dose of 20 mg twice daily if patients demonstrated a lack of efficacy.
From baseline to week 24, the median percentage reduction in spleen volume was 17.3%, and 57.8% (26) of patients experienced a volume reduction of at least 10%. A clear dose-response relationship was observed, with spleen volume reductions of 20.1% and 32.9% among patients receiving ruxolitinib 20-30 mg and 30-40 mg, respectively.
The Myelofibrosis Symptom Assessment Form v2.0 diary total symptom score (MFSAF TSS) was used to assess MF symptoms, and results showed that patients had a median percentage reduction of 45.6% from baseline to week 24. A clear dose response was observed again; patients receiving the higher ruxolitinib dose had the greatest reduction in symptom score.
Reports of grade 3 to 4 anemia (20.0%), and dose adjustments attributed to anemia (11.1%) or thrombocytopenia (6.7%) were uncommon; previous studies of ruxolitinib reported that 45.2% and 42% of patients experienced grade 3 or 4 anemia, respectively, with ruxolitinib standard dosing. Other frequently observed AEs included arthralgia and fatigue.
The authors concluded “that initiating therapy at lower doses can be performed safely and may provide clinical benefit, including improvements in splenomegaly and symptoms, in patients with MF for whom anemia is, or is likely to become, a concern while receiving treatment with ruxolitinib.”
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[published online August 7, 2018]. J Hematol Oncol. doi: 10.1186/s13045-018-0642-0