The telomerase inhibitor imetelstat may provide significant benefits for patients with heavily transfusion dependent (TD) non-del(5q) lower-risk myelodysplastic syndromes (LR-MDS) that is relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESAs), according to the latest results from the IMerge trial ( Identifier: NCT02598661) presented at the ASCO Annual Meeting 2023.

Results from this phase 3, randomized, double-blind, placebo-controlled study showed that in this patient population, imetelstat was found to have statistically significant and clinically meaningful efficacy with high 8-week and 24-week transfusion independent (TI) rates. Further, this agent appeared to help prolong TI duration and increase hemoglobin.

“Imetelstat has demonstrated patients who are getting a median of 6 units of blood per 8 weeks [led] to a transfusion independence of almost 40% durability with 51 weeks of median transfusion independence and a median hemoglobin rise of 3.6 grams,” Amer Zeidan, MBBS, an associate professor of Internal Medicine (Hematology) and an assistant medical director for hematologic malignancies at Yale Cancer Center and Smilow Cancer Hospital, New Haven, Connecticut, said in an email interview.

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Dr Zeidan, who presented the findings, noted that in the phase 2 study of the IMerge study, heavily RBC TD ESA R/R non-del(5q) LR-MDS patients naïve to lenalidomide and hypomethylating agents (len/HMA) treated with imetelstat were able to achieve durable and continuous transfusion independence (TI).

In the current study, patients were randomly assigned to receive imetelstat 7.5 mg/kg or placebo every 4 weeks. A total of 118 patients received Imetelstat and 60 received placebo.

The primary endpoint was met and 39.8% of patients in the imetelstat arm versus 15.0% in the placebo arm achieved 8-week TI. The rate of 8-week TI was significantly higher with imetelstat in all subgroups, including RS-negative patients.

As of October 2022, the median TI duration was 51.5 weeks in the imetelstat arm vs 13.3 weeks in the placebo arm (P <0.001). Patients in the imetelstat arm had significantly higher mean hemoglobin (P <0.001) and fewer transfusions (P =0.042) over time compared to the placebo arm.

The researchers also explored variant allele frequency (VAF) changes and in 3 of 4 genes frequently mutated in MDS. VAF reduction was significantly greater in patients treated with imetelstat than placebo for those with mutations in SF3B1 (P <0.001), TET2 (P =0.032), DNMT3A (P =0.019) and ASXL1 (P =0.146). Further, the SF3B1 VAF reduction directly correlated with longer TI duration (P <0.001).

In the imetelstat arm, the most common non-hematologic treatment-emergent adverse events (TEAEs; ≥10%) were asthenia, COVID-19 (including symptomatic, asymptomatic, and COVID-19 pneumonia), peripheral edema, headache, diarrhea, and alanine aminotransferase increase.

The rates of grade ≥3 bleeding and infections in both arms were similar and the most common grade 3/4 AEs were thrombocytopenia and neutropenia. “In terms of side effects, there were no new signals detected. The most common side effects, as expected, were hematologic,” said Dr Zeidan in his presentation.

The researchers considered the clinical activity of the agent in terms of response rate impressive. Dr Ziden also noted the hemoglobin rise and durability with imetelstat were significant.

Additionally, the novelty of imetelstat’s mechanism of action as a first-in-class telomerase inhibitor and the preliminary evidence of disease modification were notable. “For patients with lower risk MDS, beyond the improvement of anemia, we are seeing signs of modification of the disease,” said Dr Zeidan


Zeidan AM, Platzbecker U, Santini V, et al. IMerge: Results from a phase 3, randomized, double-blind, placebo-controlled study of imetelstat in patients (pts) with heavily transfusion dependent (TD) non-del(5q) lower-risk myelodysplastic syndromes (LR-MDS) relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESA)v. ASCO 2023. June 2-6, 2023. Abstract 7004.