Imetelstat Reduce Red Blood Cell Transfusions in Lower-Risk Myelodysplastic Syndromes

Imetelstat presents a unique mode of action, providing long-lasting transfusion independence (around 1 year) and exhibiting disease-modifying effects for extensively transfused lower-risk myelodysplastic syndromes (LR-MDS) patients who do not respond to or are not eligible for erythropoiesis-stimulating agents (ESAs), finds an article published in The Lancet.

Patients with LR-MDS dependent on red blood cell transfusions, who do not respond to or are ineligible for erythropoiesis-stimulating agents, continue to face unmet medical needs. This investigation compared the rate of red blood cell transfusion independence (RBC-TI) between imetelstat and a placebo in patients with red blood cell transfusion-dependent LR-MDS.

The phase 3 of the IMerge study encompassed 118 sites across 17 countries included university hospitals, cancer centers, and outpatient clinics, patients aged 18 years or older with ESA-relapsed, ESA-refractory, or ESA-ineligible LR-MDS were randomly assigned (2:1) through a computer-generated schedule to receive either imetelstat 7.5 mg/kg or a placebo.

The 2-hour intravenous infusion occurred every 4 weeks until disease progression, unacceptable toxic effects,or withdrawal of consent. Randomization was stratified based on previous RBC transfusion burden and IPSS risk group. The primary endpoint was 8-week RBC-TI, defined as the proportion of patients without RBC transfusions for at least 8 consecutive weeks starting from the day of randomization until subsequent anti-cancer therapy, if any. 

The key findings of this study were:

1.From September 11, 2019, to October 13, 2021, a total of 178 patients were enrolled and randomly assigned, with 111 (62%) being male and 67 (38%) female.

2.By the data cutoff, 91 (77%) out of 118 patients had discontinued treatment in the imetelstat group, and 45 (75%) in the placebo group; additionally, one patient in the placebo group did not receive treatment.

3.The median follow-up was 19.5 months in the imetelstat group and 17.5 months in the placebo group. In the imetelstat group, 47 patients achieved an RBC-TI of at least 8 weeks, compared to nine in the placebo group.

4.Overall, 107 (91%) out of 118 patients receiving imetelstat and 28 (47%) out of 59 patients receiving placebo experienced grade 3–4 treatment-emergent adverse events.

5.The most common grade 3–4 adverse events in patients taking imetelstat were neutropenia and thrombocytopenia.

Imetelstat, a competitive telomerase inhibitor, provides lasting independence from red blood cell (RBC) transfusions for extensively transfused individuals with LR-MDS who do not respond to or are ineligible for ESAs.

Source: 

Platzbecker, U., Santini, V., Fenaux, P., Sekeres, M. A., Savona, M. R., Madanat, Y. F., Díez-Campelo, M., Valcárcel, D., Illmer, T., Shah, S., Xia, Q., Sun, L., Wan, Y., Huang, F., … Zeidan, A. M. (2023). Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial. In The Lancet. Elsevier BV. https://doi.org/10.1016/s0140-6736(23)01724-5