Phase III Trial Data: Imetelstat Sustains Transfusion Independence, Overall Survival in MDS

The phase III IMerge trial evaluated use of imetelstat to achieve red blood cell (RBC) transfusion independence (TI) in patients with transfusion-dependent, lower-risk myelodysplastic syndrome without chromosome 5 long arm deletion. New data from the trial show that imetelstat produces durable RBC TI and improves hemoglobin level in this patient population. The findings were presented at the Society of Hematologic Oncology 2024 Annual Meeting in Houston, Texas.

“Preliminary [overall survival (OS)] analysis suggests no detriment with imetelstat versus placebo,” noted lead author Valeria Santini, MD, of the University of Florence in Italy.

In this international, randomized, double-blind, placebo-controlled trial, the enrolled patients had disease that was relapsed or refractory or who were ineligible to receive erythropoiesis-stimulating agents who were also naïve to lenalidomide or hypomethylating agents. In total, 118 patients received intravenous imetelstat 7.5 mg/kg and 60 received placebo, continuing every four weeks until disease progression, unacceptable toxicity, or withdrawal of consent.

Among the patients who received imetelstat, 47 achieved RBC-TI of at least eight weeks. They had a median RBC TI duration of 52 weeks and a median increase from baseline central hemoglobin of 3.6 g/dL. Among patients who received placebo, nine achieved RBC TI of at least eight weeks. They had a median RBC TI duration of 13 weeks and a median increase from baseline central hemoglobin of 0.8 g/dL.

The study reported that 33 patients on imetelstat achieved RBC TI lasting for at least 24 weeks, with a median RBC TI duration of 80 weeks and a median hemoglobin increase of 4.2 g/dL. In addition, 21 patients had independence, which lasted for at least one year, with a median RBC TI duration of 132 weeks and a median hemoglobin increase of 5.2 g/dL.

Two patients on placebo achieved RBC TI lasting for at least 24 weeks, and they had a median hemoglobin increase of 1.1 g/dL. One of those patients had independence, which lasted for at least one year, with an RBC TI duration of 131 weeks and hemoglobin increase of 1.7 g/dL.

The patients who received imetelstat had a median follow-up of 32 months and a median OS of 40.4 months. They had a 2-year OS rate of 78%, and that rose to 81% among patients who had achieved RBC TI of at least 8 weeks.

The IMerge trial is funded by Geron Corporation.

Reference

Santini V, Komrokji RS, Sekeres MA, et al. Overall survival (OS), clinical benefit, and durable red blood cell (RBC) transfusion independence (TI) with imetelstat in the IMerge phase 3 trial of RBC-transfusion dependent (TD) lower-risk myelodysplastic syndromes (LR-MDS). Abstract #MDS-157. Presented at the Society of Hematologic Oncology 2024 Annual Meeting; September 4-7, 2024; Houston, Texas.