Imetelstat, a novel telomerase inhibitor, has emerged as a new treatment option for lower-risk (LR) MDS patients.¹Bewersdorf JP, Zeidan AM. Ann Hematol. 2020 Apr;99(4):677-692. Telomere shortening and dysregulation of telomerase activity have been associated with inferior survival in MDS.¹Bewersdorf JP, Zeidan AM. Ann Hematol. 2020 Apr;99(4):677-692. Imetelstat is currently being investigated in IMerge, a phase 2/3 global study, for transfusion-dependent patients with LR MDS and relapsed or refractory to erythropoietin stimulating agents (ESA R/R).²Platzbecker U. Abstract S183. Presented at the European Hematology Association 2020 (June 11-21). Available at: https://ww3.mdne.ws/3fGlVXS (Accessed 7 July 2020). The long-term efficacy and safety results of this trial were reported at the European Hematology Association 25^th Annual Congress in 2020.

Patients received imetelstat 7.5mg/kg IV Q4W, and 38 LR non-del(5q) transfusion-dependent ESA R/R MDS patients were followed for a median of 24 months.²Platzbecker U. Abstract S183. Presented at the European Hematology Association 2020 (June 11-21). Available at: https://ww3.mdne.ws/3fGlVXS (Accessed 7 July 2020). Long-term efficacy outcomes included ≥8-week, ≥24-week, and ≥1-year RBC transfusion-independence (TI) rates, longest and cumulative duration of ≥8-week TI, duration of haematologic improvement-erythroid, and major/minor response according to updated International Working Group (IWG) 2018 guidelines.²Platzbecker U. Abstract S183. Presented at the European Hematology Association 2020 (June 11-21). Available at: https://ww3.mdne.ws/3fGlVXS (Accessed 7 July 2020). All 38 patients had a high transfusion burden (≥4 units per 8 weeks), and 84% had a burden of ≥6 units per 8 weeks.²Platzbecker U. Abstract S183. Presented at the European Hematology Association 2020 (June 11-21). Available at: https://ww3.mdne.ws/3fGlVXS (Accessed 7 July 2020). Of all participants, 89% had received prior ESAs, and 32% had EPO levels exceeding 500U/L.²Platzbecker U. Abstract S183. Presented at the European Hematology Association 2020 (June 11-21). Available at: https://ww3.mdne.ws/3fGlVXS (Accessed 7 July 2020).

In these 38 patients, 42% had ≥8-week TI, 32% achieved ≥24-week TI, and 29% with a median transfusion burden of 6 units per 8 weeks were transfusion-free for over 1-year.²Platzbecker U. Abstract S183. Presented at the European Hematology Association 2020 (June 11-21). Available at: https://ww3.mdne.ws/3fGlVXS (Accessed 7 July 2020). Clinically meaningful major and minor responses (16-week TI and 50% transfusion reduction/16 weeks) were achieved by 37% and 55% of patients, per IWG guidelines.²Platzbecker U. Abstract S183. Presented at the European Hematology Association 2020 (June 11-21). Available at: https://ww3.mdne.ws/3fGlVXS (Accessed 7 July 2020). The 42% 8-week TI rate is the longest reported with any agent in non-del(5q) LR-MDS patients. Grade ≥3 cytopenias were the most frequently reported adverse events but were manageable and reversible.²Platzbecker U. Abstract S183. Presented at the European Hematology Association 2020 (June 11-21). Available at: https://ww3.mdne.ws/3fGlVXS (Accessed 7 July 2020).

Over 50% reduction of telomerase activity and human telomerase reverse transcriptase (hTERT) RNA levels post-imetelstat dosing were used to demonstrate on-target imetelstat activity, which was observed in 23.1% and 54.3% of patients, respectively.²Platzbecker U. Abstract S183. Presented at the European Hematology Association 2020 (June 11-21). Available at: https://ww3.mdne.ws/3fGlVXS (Accessed 7 July 2020). A significantly higher proportion of patients had ≥50% hTERT expression reduction when achieving ≥8-week TI compared with patients without TI (80% vs. 35%; p=0.0155).²Platzbecker U. Abstract S183. Presented at the European Hematology Association 2020 (June 11-21). Available at: https://ww3.mdne.ws/3fGlVXS (Accessed 7 July 2020). This was also seen in patients achieving ≥24-week TI vs. patients without TI (91.7% vs. 34.8%; p=0.0016). This indicates there may be a correlation between telomerase inhibition and clinical benefit.²Platzbecker U. Abstract S183. Presented at the European Hematology Association 2020 (June 11-21). Available at: https://ww3.mdne.ws/3fGlVXS (Accessed 7 July 2020).