Geron Corporation's RYTELO™ (imetelstat) continues to show promise in treating lower-risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia, according to new analyses presented at the 66th American Society of Hematology (ASH) Annual Meeting. The data suggest that imetelstat, a first-in-class telomerase inhibitor, demonstrates clinical activity regardless of the type or number of prior therapies patients have received. These findings offer physicians important clinical evidence for assessing treatment sequencing in this challenging patient population.
Broad Clinical Activity Across Treatment Histories
The analyses, which pooled data from the IMerge Phase 2, Phase 3, and QTc substudy, included 226 imetelstat-treated LR-MDS patients. A significant 90% had prior treatment with an erythropoiesis-stimulating agent (ESA), while 12% had prior lenalidomide, 16% luspatercept, and 10% a hypomethylating agent (HMA). The median imetelstat treatment duration was 33.6 weeks. Results indicated that patients who were ESA ineligible or had prior treatment with luspatercept or lenalidomide experienced similar clinical benefits from imetelstat as seen in the IMerge Phase 3 pivotal trial. Patients with prior HMA treatment showed more modest clinical activity.
According to Rami S. Komrokji, M.D., Vice Chair, Malignant Hematology Department, Moffitt Cancer Center, “The IMerge data presented at ASH suggesting clinical activity of imetelstat regardless of prior therapies, offers physicians important clinical evidence while assessing sequencing of treatments.”
QTc Substudy Reinforces Safety Profile
Initial results from the QTc substudy of IMerge Phase 3, which included patients with del(5q) MDS and allowed prior lenalidomide and HMA therapy, further support imetelstat's safety profile. The substudy comprised 53 patients (35 imetelstat, 18 placebo), with 16 placebo recipients crossing over to imetelstat. The data cutoff was May 10, 2024. In the total imetelstat population (n=51), 41% achieved ≥8-week red blood cell transfusion independence (RBC-TI), and 25% achieved ≥24-week RBC-TI.
Notably, patients treated with imetelstat showed no treatment-related changes in cardiac repolarization compared with placebo, reinforcing imetelstat as a second-line treatment option for LR-MDS patients with transfusion-dependent anemia regardless of prior therapies, including luspatercept and lenalidomide.
Patient-Reported Outcomes Highlight Improved Quality of Life
An exploratory patient-reported outcome (PRO) analysis from IMerge Phase 3, with a data cutoff of October 2022, assessed fatigue, anemia symptoms, and quality of life using validated questionnaires. The PRO population (n=175) included 118 imetelstat-treated patients and 57 placebo patients. Results showed that more imetelstat-treated patients reported sustained improvement in fatigue, regardless of ring sideroblast (RS) status, prior transfusion burden, and baseline serum EPO levels. Additionally, improvements in fatigue correlated with RBC-TI, hemoglobin rise, and transfusion reduction.
Faye Feller, M.D., Executive Vice President, Chief Medical Officer of Geron, stated, “The sustained improvement in fatigue observed in the IMerge Phase 3 patient-reported outcomes population is meaningful for this progressive disease that is characterized by fatigue.”
Regulatory and Clinical Context
RYTELO™ (imetelstat) is an FDA-approved oligonucleotide telomerase inhibitor for adult patients with low-to-intermediate-1 risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia requiring four or more red blood cell units over eight weeks who have not responded to or are ineligible for erythropoiesis-stimulating agents (ESAs). It is administered intravenously every four weeks. The drug's safety profile includes warnings and precautions for thrombocytopenia, neutropenia, and infusion-related reactions.
Geron is also conducting a pivotal Phase 3 clinical trial of imetelstat in JAK-inhibitor relapsed/refractory myelofibrosis (R/R MF), as well as studies in other hematologic malignancies.
