Updated analysis of overall survival with imetelstat in relapsed/refractory myelofibrosis versus real-world data, and assessment of real-world treatment patterns

In a previous analysis of the phase 2 IMbark trial, imetelstat showed significantly longer median overall survival (mOS) in patients with Janus kinase inhibitor relapsed/refractory (R/R) intermediate-2–risk or high-risk myelofibrosis than in a closely matched real-world (RW) cohort treated with best available therapy (BAT) after ruxolitinib. Because the evolving myelofibrosis treatment landscape may influence outcomes, an updated OS analysis compared IMbark patients with a larger RW cohort after extended follow-up and explored changes in RW treatment patterns over this period. The RW dataset included 126 patients at Moffitt Cancer Center who discontinued ruxolitinib and received BAT between 2010 and 2025. Comparing treatment patterns for patients diagnosed before/after 2016 and 2019 showed significant reductions in the time from diagnosis to ruxolitinib initiation and in ruxolitinib treatment duration. Patients diagnosed after 2016/2019 had notably longer mOS than those diagnosed before 2016/2019. For the updated survival analysis between IMbark patients treated with imetelstat ( n = 59) and matched RW patients treated with BAT ( n = 54), median follow-up periods were 46.2 and 48.2 months, respectively. In the historical comparison of patients diagnosed before 2016, OS was longer among patients treated with imetelstat in IMbark than among those treated with BAT (mOS, 30.7 vs. 15.4 months; hazard ratio = 0.512; P =.003), with similar findings after propensity score adjustment. The significant improvement in OS among RW patients over the past decade may be attributable to shorter time to ruxolitinib initiation and earlier transitions to next-line therapies or clinical trials. Evolving treatment patterns are key considerations when interpreting future clinical trial outcomes. Trial registration ClinicalTrials.gov, NCT02426086 April 21, 2015.