No Effect of Immunogenicity on Pharmacokinetics, Efficacy, and Safety of the Oligonucleotide Telomerase Inhibitor Imetelstat in Lower‐Risk Myelodysplastic Syndromes

Dec 14, 2025Clinical and translational science

Immune response does not affect how the telomerase inhibitor Imetelstat works or its safety in lower-risk myelodysplastic syndromes

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Abstract

16.9% of patients developed (ADAs) after receiving imetelstat for lower-risk myelodysplastic syndromes.

The median time to onset of ADAs was 38 weeks, with a range of 12 to 109 weeks.
In ADA-positive patients, the peak antibody titer was low, with a median of 30.
No association was found between ADA positivity and the pharmacokinetics or efficacy responses of imetelstat.
Overall treatment-emergent adverse event rates were similar between ADA-positive and ADA-negative groups.
Infusion-related adverse events were reported more frequently in ADA-positive patients, although the group was small.

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Imetelstat is a first-in-class, 13-mer oligonucleotide telomerase inhibitor approved in the United States and European Union for the treatment of certain adult patients with lower-risk myelodysplastic syndromes (LR-MDS) with red blood cell () transfusion-dependent anemia. This post hoc analysis evaluated imetelstat immunogenicity and its association with the pharmacokinetics (PK), efficacy, and safety of imetelstat in patients with LR-MDS from the phase II/III IMerge study (NCT02598661). A validated, semi-quantitative 3-tiered method evaluated (ADAs). Graphical and descriptive analyses evaluated ADA incidence and association with clinical outcomes. Of 166 evaluable patients who received 7.1 mg/kg imetelstat via a 2-h intravenous infusion every 4 weeks, 16.9% developed imetelstat ADAs (median [range] time to onset, 38 weeks [12-109]; ~8 treatment cycles). In ADA-positive patients, peak titer was low (median [range], 30 [10-160]). Evaluations showed no association of ADA positivity with imetelstat PK, nor any negative association with efficacy responses, including ≥ 8-week RBC-transfusion independence (TI), ≥ 24-week RBC-TI, hematologic improvement-erythroid, or duration of RBC-TI response. There was no apparent relationship between the onset of ADAs and loss of RBC-TI. The rates of any-grade or grade ≥ 3 treatment-emergent adverse events (TEAEs) were similar for both ADA groups, with no reported serious TEAEs or TEAEs causing death in ADA-positive patients. Infusion-related TEAEs were more frequent in ADA-positive patients, although the sample size was small. Overall, imetelstat ADAs did not appear to impact imetelstat benefit/risk profile in the LR-MDS population of IMerge, although the analysis is limited by the low incidence of imetelstat ADAs, resulting in a small ADA-positive group.

Key numbers

28 of 166

Incidence

Patients with treated with imetelstat.

38 weeks

Median Time to Onset

Time from treatment initiation to detection.

18 of 28

Efficacy Rate for ≥ 8-week -

-positive patients achieving transfusion independence.

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No Effect of Immunogenicity on Pharmacokinetics, Efficacy, and Safety of the Oligonucleotide Telomerase Inhibitor Imetelstat in Lower‐Risk Myelodysplastic Syndromes

Abstract

Key numbers

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