Patients with lower-risk MDS benefit from imetelstat

Patients with Low or Intermediate-1 risk myelodysplastic syndrome (lower-risk MDS) experienced meaningful and durable transfusion independence when treated with imetelstat.

Prof. Uwe Platzbecker (University Clinic Leipzig, Germany) presented the phase 2 results from the phase 2-3 IMerge clinical trial [1]. IMerge evaluated the novel telomerase inhibitor imetelstat as a treatment for patients with lower-risk MDS, who had relapsed after or were refractory to treatment with erythropoiesis-stimulating agents (ESAs). The primary efficacy endpoint of IMerge was 8-week RBC transfusion independence (RBC-TI) rate, for any 8 consecutive weeks since trial entry. Key secondary endpoints included rate of haematologic improvement-erythroid (HI-E) and duration of TI.

In the open label, single arm, phase 2 stage of IMerge, 38 patients were treated with imetelstat, with a median follow-up of 24 months. The initial results indicate that the primary endpoint was met; 16 patients (42%) achieved 8-week TI, and 12 of those responders (75%) showed a haemoglobin rise of >3 g/dL compared to pre-treatment during the transfusion-free interval. With regard to the secondary endpoints, 68% reached HI-E. Furthermore, the median duration of TI was 20 months, while the median duration of HI-E was 21 months. Although preliminary, 29% of patients were transfusion-free for >1 year, which may indicate potential disease-modifying activity. The longest transfusion-free interval was 2.7 years. Most frequently reported adverse events were manageable and reversible grade >3 cytopenias.

The phase 3 stage of IMmerge is a double-blind, randomised, placebo-controlled clinical trial with registration intent, which is currently recruiting patients. It will enrol approximately 170 patients with lower-risk transfusion-dependent MDS who are relapsed or refractory to an ESA, have not received prior treatment with either a hypomethylating agent (HMA) or lenalidomide, and who are non-del(5q).

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   1. Platzbecker U, et al. Treatment with imetelstat provides durable transfusion independence (TI) in heavily transfused non-del(5Q) lower risk MDS (LRMDS) relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESA). EHA25 Virtual, 11-21 June 2020, Abstract S183.

Posted on 9 September 202016 February 2024