Evaluation of an alternative ruxolitinib dosing regimen in patients with myelofibrosis: an open-label phase 2 study
JournalJournal of Hematology and Oncology
PublisherBioMed Central Ltd.
MetadataShow full item record
AbstractBackground: 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. Copyright 2018 The Author(s).
SponsorsWe gratefully acknowledge the assistance of Ramon Tiu, MD, as the coordinating principal investigator for this study. Medical writing assistance was provided by Tania R. Iqbal, PhD, of Complete Healthcare Communications, LLC (West Chester, PA), a CHC Group company, and was funded by Incyte Corporation (Wilmington, DE).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85051194971&doi=10.1186%2fs13045-018-0642-0&partnerID=40&md5=8322c5c23ccb04b652fa288166c876b8; http://hdl.handle.net/10713/9066