EHA 2023 | IMerge results: efficacy and disease-modifying activity of imetelstat in LR-MDS after ESA failure
Uwe Platzbecker, MD, University of Leipzig, Leipzig, Germany, summarizes the findings of the Phase III IMerge study (NCT02598661), investigating imetelstat in patients with lower-risk myelodysplastic syndromes (LR-MDS) with high transfusion burden, and who are relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESA). This trial met its primary endpoint, with significantly more patients achieving infusion independence with imetelstat compared to a placebo. Prof. Platzbecker discusses the safety and efficacy data from the trial and notes that patients with known mutations showed a decline in allelic burden, demonstrating the disease-modifying activity of imetelstat. This interview took place at the 28th Congress of the European Hematology Association (EHA) 2023 in Frankfurt, Germany.
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Transcript (edited for clarity)
So IMerge was a Phase III trial which investigated imetelstat, a first-in-class telomerase inhibitor, in patients with low-risk MDS according to the IPSS, IPSS low-intermediate 1, versus placebo – there was actually 2:1:1 randomization. And, apart from the IPSS, one inclusion criteria was also a transfusion burden of at least four units of red blood cells within eight weeks, so majority of patients actually had a high transfusion burden...
So IMerge was a Phase III trial which investigated imetelstat, a first-in-class telomerase inhibitor, in patients with low-risk MDS according to the IPSS, IPSS low-intermediate 1, versus placebo – there was actually 2:1:1 randomization. And, apart from the IPSS, one inclusion criteria was also a transfusion burden of at least four units of red blood cells within eight weeks, so majority of patients actually had a high transfusion burden. Also, ESA therapy was required, and also failure to ESA therapy was required. So basically the trial included a typical lower-risk population with a high transfusion burden. And also, the median age and everything like this I think resembled very well a typical MDS cohort of patients.
The trial actually met its primary endpoint, which was red blood cell transfusion independence of at least eight weeks. There was a statistically significant difference, with almost 40% response rate in the imetelstat arm. Apart from, I think, the neutropenia and the thrombocytopenia, which is a known side effect of imetelstat and could be managed pretty well in the majority of the patients with no dose delays, the trial basically did not reveal any new safety signals.
There was also a translational work presented at the EHA meeting, which showed that patients with a known mutation like SF3B1 of DNMT3A actually had a decline, a significant decline – sometimes by 100% percent – of the allelic burden of the mutation, which shows that the drug has obviously disease-modifying activity. And actually this reduction, or this affection, of the clonal cells also correlated with the clinical response.
So, to make a long story short now, we hope that the trial will result in the approval of this agent for lower-risk MDS patients failing first line therapy with an ESA.
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Disclosures
Grant support, paid to GWT-TUD, from Amgen; lecture fees and grant support, paid to the University of Leipzig, from Amgen; fees for serving on a steering committee, consulting fees, and travel support from Bristol Myers Squibb; grant support, paid to GWT-TUD, from Janssen Biotech; grant support, paid to University Dresden, from Merck and Novartis; lecture and consulting fees from Novartis; and consulting fees from AbbVie, Curis, and Geron.
