Zeidan Recaps the Phase 3 IMerge Trial of Imetelstat in Lower-Risk MDS

Amer Zeidan, MBBS, Yale Cancer Center, discusses the rationale of studying imetelstat in the phase 3 IMerge trial (NCT02598661) in patients with heavily transfusion dependent, non-del(5q) lower-risk myelodysplastic syndrome (MDS) that is relapsed or refractory to erythropoiesis stimulating agents.

According to results from the study, response rates with imetelstat were high and durable, and the trial met its primary end point of 8-week transfusion independence, as well as a key secondary end point of 24-week transfusion independence.

In addition, the safety results observed in the trial were consistent with prior clinical trials of imetelstat.

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0:10 | Imetelstat is a first-in-class telomerase inhibitor. It works by inhibiting the telomerase and early phase data suggested that this could have selective pressure on the clonal cells within patients with MDS, leading to the killing of the MDS clone and the recovery of the count in those patients.

0:32 | The rationale for the IMerge randomized, phase 3 trial was based on the phase 2 trial, which is part of the same trial, but it was a single-arm part where 40 patients with lower-risk MDS who had heavy transfusion dependence but had no previous exposure to lenalidomide or to hypomethylating agents were enrolled in the phase 2 part of the study. Importantly, the transition dependence rate was quite good at around 40%. Those patients had durable responses.

1:10 | We presented an update at ASH 2022 looking at the long-term outcome of the 11 patients who had transfusion independence lasting more than 1 year, and the response rate was high, it was durable, and importantly, we saw early evidence of disease modification, which we inferred by a reduction in the allele frequency of several genes that are involved in the pathogenesis of MDS.

1:38 | On the adverse effect side, the main effects were liver enzyme abnormalities, but most of those were grade 1 and grade 2, and generally reversible, as well as thrombocytopenia and neutropenia, and while those were grade 3 and grade 4, most of them are reversible and manageable, meaning that when you hold the drug, they basically go back to grade 2 or less 80% of the time within 4 weeks. There was [also] no increase in the rates of significant clinical consequences, for example, severe infection or bleeding with the drug.