Imetelstat Versus Best Available Therapy in Patients with Intermediate-2 or High-Risk Myelofibrosis Relapsed or Refractory to Janus Kinase Inhibitor in IMpactMF, a Randomized, Open-Label, Phase 3 Trial

作者：John Mascarenhas, Claire Harrison, Prithviraj Bose, Jean‐Jacques Kiladjian, Alessandro Lucchesi, Alessandro Maria Vannucchi, Tymara Berry, Jennifer R. Riggs, Lixian Peng, Fei Huang, Ying Wan, Vivian Rodolf, Judy Ho, Shyamala Navada, Rami S. Komrokji · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-199235 · 被引用次数：6 · 研究领域：Myeloproliferative Neoplasms: Diagnosis and Treatment、Acute Myeloid Leukemia Research

Introduction: Myelofibrosis (MF) is a myeloproliferative neoplasm with limited disease-modifying treatment options. For patients (pt) who are relapsed or refractory (R/R) to Janus kinase inhibitors (JAKi), clinical outcomes are poor with a median overall survival (OS) of ≈1 year (Kuykendall 2018), indicating a need for additional treatment options in this pt population. Imetelstat is a first-in-class telomerase inhibitor approved in 2024 for the treatment of pts with transfusion-dependent lower-risk myelodysplastic syndromes who are R/R/ineligible for erythropoiesis-stimulating agents. In the phase 2 IMbark trial (NCT02426086; Mascarenhas 2021), pts were randomly assigned to receive 9.4 mg/kg or 4.7 mg/kg imetelstat sodium (equivalent to 8.9 mg/kg and 4.4 mg/kg imetelstat active doses), respectively. In pts with JAKi R/R intermediate-2 (Int2) or high-risk (HR) MF, imetelstat at 9.4 mg/kg once every 3 weeks demonstrated meaningful clinical improvement. Symptom response (total symptom score [TSS] reduction ≥50% per the modified Myelofibrosis Symptom Assessment Form) was observed in 32% (19/59) of pts at week 24. Spleen response (spleen volume reduction ≥35%) was observed in 10% (6/59) of pts at week 24. Median OS was 29.9 months after median study follow-up of 27.4 months. Imetelstat treatment improved bone marrow (BM) fibrosis and reduced variant allele frequency (VAF) of MF driver mutations in a dose-dependent manner. BM fibrosis improvement and VAF reduction correlated with ...