IMproveMF update: Imetelstat plus ruxolitinib in patients with MF

Myelofibrosis (MF) is a progressive MPN associated with driver mutations in JAK2, CALR, or MPL. Although JAK inhibitors can reduce the symptom burden of MF, they are unable to target underlying driver mutations. 

Imetelstat is a first-in-class telomerase inhibitor that demonstrated potential survival improvements and disease-modifying activity in the phase II IMbark trial (NCT02426086). During the 2025 ASCO Annual Meeting, John Mascarenhas presented updated results from phase I/Ib of the IMproveMF trial (NCT05371964) evaluating the safety and efficacy of the imetelstat and ruxolitinib combination in patients with intermediate-1, intermediate-2, or high-risk MF.¹

In part I of the trial, eligible patients (N = 19) received ruxolitinib 5–25 mg twice a day and imetelstat at dose levels of 4.4 mg/kg, 5.6 mg/kg, 7.1 mg/kg, and 8.9 mg/kg every 28 days. The primary endpoints were AEs and symptom response rate at Week 24. Secondary endpoints included pharmacokinetics and clinical activity.

Key learnings

The combination was generally well tolerated. No DLTs were reported with imetelstat at any dose level within the first 28 days of C1. Grade ≥3 TEAEs occurred in 48% of patients, while no Grade 5 TEAEs were reported.

Patients receiving imetelstat achieved a reduction in TSS from baseline to up to 24 weeks, as well as a decrease in spleen volume.

The pharmacokinetic profile of imetelstat plus ruxolitinib was consistent with previous studies. For imetelstat, exposure was dose-dependent at C1D1, with C_max achieved at the end of the 2-hour infusion and a similar C_max across cycles for each dose level.

These early findings suggest tolerability and dose-dependent preliminary efficacy of imetelstat plus ruxolitinib, demonstrating the potential of the combination in this MF population with high unmet needs.