High-dose ruxolitinib (25 mg twice daily) in myelofibrosis: feasibility, safety, and long-term treatment exposure in a real-world cohort

BackgroundRuxolitinib is standard first-line therapy for symptomatic myelofibrosis (MF). In real-world practice, dose reductions are common, and the impact of maintaining higher dose intensity over time remains incompletely characterized-particularly for patients escalated to 25 mg twice daily (50 mg/day; full dose).MethodsWe conducted a single-center retrospective cohort study of consecutive MF patients (2015-2025) who received 25 mg BID at least once during their treatment course. Data were extracted from a structured institutional database linking baseline (DEMOGRAPHY) and visit-level longitudinal data (HISTORY), including dosing, supportive care, infections, transfusions, and spleen measurements. Dose-intensified exposure was defined as 40 mg/day or higher and was used to anchor t0 (first visit at 40 mg/day or higher), while full-dose exposure specifically referred to the approved maximum of 50 mg/day (25 mg twice daily). FRAC_EQ50 quantified sustained full-dose exposure as the fraction of visits at 50 mg/day. Analyses were descriptive.ResultsTwenty-four patients were included, with a median follow-up of 60.9 months from ruxolitinib initiation. Based on FRAC_EQ50, 11/24 patients were classified as high-intensity (FRAC_EQ50 0.50-1.00), 6/24 as intermediate (0.10-0.49), and 7/24 as minimal (below 0.10). For spleen-response analyses, baseline was defined as the first ultrasound spleen length recorded after t0 and was available in 22/24 patients; spleen response was evaluable in 21/24 (one patient lacked a follow-up ultrasound with spleen length in cm; two had no evaluable post-baseline spleen assessments). Spleen length decreased in 17/21 evaluable patients (81.0%), while hematologic toxicities and supportive-care needs remained manageable across intensity groups. Four deaths occurred during follow-up, including one fatal COVID-19 case temporally associated with abrupt ruxolitinib discontinuation during ICU intubation.ConclusionsIn selected MF patients, escalation to 25 mg BID with sustained full-dose intensity appears feasible in routine practice, with durable treatment exposure and manageable safety. These real-world data support further multicenter efforts to better characterize longitudinal dose exposure and its potential clinical implications, without implying causal relationships.