Clinical Summary: 

• Design/Population: This updated post hoc analysis compared overall survival in patients with JAK inhibitor relapsed or refractory myelofibrosis treated with imetelstat in the phase 2 IMbark trial versus a contemporary, closely matched real-world cohort receiving best available therapy after ruxolitinib discontinuation.
• Key Outcomes: Imetelstat continued to demonstrate a significant overall survival advantage over best available therapy despite improvements in real-world outcomes over the past decade. Earlier initiation of ruxolitinib and shorter time to subsequent therapy were associated with improved survival in the contemporary real-world cohort.
• Clinical Relevance: These findings support the potential survival benefit of imetelstat while emphasizing the importance of evolving treatment patterns when interpreting contemporary clinical trial results.

Updated results from a post hoc analysis demonstrated that imetelstat continued to improve overall survival (OS) compared with best available therapy in patients with Janus kinase (JAK) inhibitor relapsed or refractory myelofibrosis, despite substantial changes in real-world treatment patterns over the past decade.

These results were presented by Andrew Kuykendall, MD, Moffitt Cancer Center, Tampa, Florida, at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Researchers analyzed data from 126 patients who discontinued ruxolitinib and subsequently received best available therapy between 2010 and 2025. To compare survival outcomes, investigators identified a closely matched cohort of 54 real-world patients using IMbark eligibility criteria and compared them with 59 patients treated with imetelstat in the IMbark trial. OS was measured from JAK inhibitor discontinuation until death or last follow-up, with propensity score weighting used to adjust for baseline characteristics and prognostic factors.

At a median follow-up of 46.2 months in the IMbark cohort and 48.2 months in the real-world cohort, median OS was 30.7 months in patients treated with imetelstat and 15.4 months in patients treated with best available therapy (hazard ratio [HR], 0.512; P = .003). Similar results were observed using propensity-weighted analyses.

Investigators also found that real-world treatment patterns have evolved substantially over time. Among patients diagnosed after 2016, the mean time from diagnosis to ruxolitinib initiation decreased from 46.7 months to 10.5 months, while mean duration of ruxolitinib treatment decreased from 30.4 months to 13.5 months. Median OS also improved from 15.4 months to 34.2 months. 

Similar trends were observed when comparing patients diagnosed before and after 2019, with mean time from diagnosis to ruxolitinib initiation decreasing from 39.7 months to 8.2 months, mean treatment duration decreasing from 26.1 months to 15 months, and median OS increasing from 16.6 months to 39.8 months.

“This updated post hoc analysis confirms a significantly more favorable OS benefit with [imetelstat vs best available therapy] in pts with [relapsed or refractory myelofibrosis] and poor prognosis consistent with the previous report,” concluded Dr Kuykendall. “Evolving [treatment] patterns are key considerations for interpreting future clinical trial outcomes.” 

Source: 

Kuykendall AT, Qasim H, Araji G, et al. 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. Presented at the 2025 ASCO Annual Meeting; May 30–June 3, 2025; Chicago, Illinois. Abstract 6573.