Updated analysis of overall survival (OS) with imetelstat (IME) in relapsed/refractory (R/R) myelofibrosis (MF) versus real-world (RW) data, and assessment of RW treatment (tx) patterns.

6573 Background: IME showed significantly longer median OS (mOS) in patients (pts) with Janus kinase inhibitor (JAKi) R/R intermediate-2–risk or high-risk MF in the IMbark trial (NCT02426086) vs closely matched RW pts treated with best available therapy (BAT) after ruxolitinib (RUX; HR, 0.35; P =.0019). The MF tx landscape changed considerably in recent years, potentially impacting OS. We present an updated OS analysis of IMbark pts vs a larger RW pt cohort after extended follow-up. Methods: The updated RW dataset included 126 pts who discontinued RUX and were subsequently treated with BAT at Moffitt Cancer Center between 2010 and 2025. To assess changes in RW tx patterns, baseline/disease characteristics and OS of pts diagnosed before/after 2016 and 2019 were compared. To update the IMbark vs RW OS analysis, a closely matched cohort was identified using IMbark eligibility criteria, including pts diagnosed before 2016 who received RUX but were R/R. The mOS was measured from time of JAKi discontinuation to death or censored at last follow-up. Propensity score approaches using average tx effect for overlap population (ATO) or stabilized inverse probability tx weighting (sIPTW) were implemented to adjust for baseline covariates/prognostic factors that may impact outcomes. Results: The RW tx pattern assessment included 96 pts. Time from diagnosis to start of RUX and duration of RUX tx were significantly shorter after 2016 vs before (Table). Similar changes were observed after 2019 vs before. The mOS in pts diagnosed after 2016 and 2019 was significantly longer vs before. The updated mOS analysis included 59 IMbark pts and 54 closely matched RW pts. With a median follow-up of 46.2 mo for IMbark pts and 48.2 mo for RW pts, mOS (95% CI) was 30.7 mo (25.5-36.9) with IME in IMbark vs 15.4 mo (13.1-30.5) with BAT in RW (HR, 0.512; P= .003) per the unweighted analysis. Propensity-weighted analyses (ATO, sIPTW) had similar results. Conclusions: This updated post hoc analysis confirms a significantly more favorable OS benefit with IME vs BAT in pts with R/R MF and poor prognosis consistent with the previous report (Kuykendall 2021). A significant improvement in OS in RW pts over the last decade was also demonstrated, potentially due to shorter time from diagnosis to start of RUX and earlier switch to next-line JAKi or clinical trial. Evolving tx patterns are key considerations for interpreting future clinical trial outcomes. Clinical trial information: NCT02426086 . Updated RW data by time of diagnosis. Before 2016(N=54) After 2016(N=42) Before 2019(N=69) After 2019(N=27) Time from diagnosis to RUX start (mean), mo 46.7 10.5 39.7 8.2 RUX duration (mean), mo 30.4 13.5 26.1 15.0 Transplant, n (%) 3 (5.6) 4 (9.5) 5 (7.2) 2 (7.4) mOS (95% CI), mo 15.4(13.1-30.5) 34.2(24.2-NA) 16.6(14.2-30.0) 39.8(34.2-NA) mOS, median overall survival; NA, not available; RUX, ruxolitinib; RW, real world.