Safety and Efficacy of Ruxolitinib in Patients with Myelofibrosis and Low Platelet Counts (50 – 100 × 109/L): Final Analysis of an Open-Label Phase 2 Study

Treatment options for myelofibrosis and platelet counts 50 - 100x10(9)/L are limited. Ruxolitinib was initiated at 5 mg twice daily with gradual up-titration based on response and hematologic parameters. Improvements in spleen volume and symptoms were greatest with ruxolitinib 10 mg twice daily. A lower starting dose of ruxolitinib with gradual up-titration and subsequent dose optimization was safe and efficacious. Introduction: Treatment options in patients with myelofibrosis (MF) presenting with thrombocytopenia are limited. Final results of the phase 2 study (NCT01348490) of ruxolitinib in patients with MF and low baseline platelet counts (50 - 100 x 10(9)/L) are reported. Patients and Methods: Patients received ruxolitinib 5 mg twice daily (BID), with optional up-titration to a maximum of 15 mg BID, provided platelet count remained >= 40 x 10(9)/L. Assessments included spleen volume and length, Total Symptom Score (TSS), quality of life, and safety. Results: Of 66 patients, 52 (78.8%) completed the first 24 weeks of treatment. Median (range) percentage change from baseline in spleen volume and TSS (coprimary endpoints) were -20.5% (-55.8% to 38.5%, n=51) and -39.8% (-98.6% to 226.4%, n=53), respectively; greatest median reductions were in the 10 mg BID final titrated dose group. Of patients achieving >= 35% or >= 10% reduction in spleen volume, 8/11 (72.7%) and 21/34 (61.8%), respectively, were in the 10 mg BID final titrated dose group. Thirty-seven of 65 patients (56.9%) had >= 20% improvement in TSS, and 35/66 patients (53.0%) were Patient Global Impression of Change responders. Treatment-emergent adverse events led to dose interruption in 17/66 patients (25.8%), most commonly thrombocytopenia (n=3). Conclusion: A starting dose of ruxolitinib 5 mg BID with gradual up-titration and dose optimization based on hematologic parameters and response was efficacious and generally well-tolerated in patients with MF and low platelet counts. Median improvement in spleen volume and symptoms was greatest for patients receiving ruxolitinib 10 mg BID. (C) 2021 The Authors. Published by Elsevier Inc.