Randomized Phase II Study of Imetelstat in Relapsed or Refractory Myelofibrosis

By Patrick Daly - Last Updated: December 7, 2021

A study published in the Journal of Clinical Oncology found that therapy with two doses of imetelstat appears to have clinical benefits for both symptom response and potential disease-modifying activity in patients with relapsed or Janus-associated kinase inhibitor (JAKi) treatment-refractory high-risk myelofibrosis (MF). John Mascarenhas, MD, the lead author of the study, said that treatment with imetelstat displayed an acceptable safety profile.

The study’s design initially included two arms that compared treatment outcomes of imetelstat 9.4mg/kg and 4.7mg/kg, administered intravenously every three weeks. However, enrollment was closed early and the 4.7mg/kg arm continued treatment at the 9.4mg/kg dose. The primary outcomes assessed after 24 weeks were spleen response rate, defined as a 35% or more spleen volume reduction, and symptom response rate, defined as a 50% or greater reduction in total symptom score. Other measures included safety and overall survival (OS).

At week 24, respective spleen and symptom response rates were 10.2% and 32.2% in the 9.4-mg/kg arm, and 0% and 6.3% in the 4.7-mg/kg arm. The 9.4 mg/kg arm had a median OS of 29.9 months. Bone marrow fibrosis improvement and variant allele frequency reduction of driver mutations were seen in 40.5% and 42.1% of evaluable patients, respectively, and both were associated with OS. Reduced telomerase activity and human telomerase reverse transcriptase levels indicated successful target inhibition, and were both correlated with spleen response, symptom response, and OS. The most frequent adverse events were grade III or IV reversible cytopenias.

As patients with relapsed or JAKi-resistant MF have very poor clinical outcomes, with OS that only ranges between 13 and 16 months, developing new treatments that “target the underlying malignant clones in MF remains a significant area of unmet need,” according to Dr. Mascarenhas. He closed with the note that a confirmatory phase III study is underway to validate the benefits of the imetelstat treatment.

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