Imetelstat Achieves Meaningful and Durable Transfusion Independence in High Transfusion-Burden Patients With Lower-Risk Myelodysplastic Syndromes in a Phase II Study

David P. Steensma*, Pierre Fenaux, Koen Van Eygen, Azra Raza, Valeria Santini, Ulrich Germing, Patricia Font, Maria Diez-Campelo, Sylvain Thepot, Edo Vellenga, Mrinal M. Patnaik, Jun Ho Jang, Helen Varsos, Jacqueline Bussolari, Esther Rose, Laurie Sherman, Libo Sun, Ying Wan, Souria Dougherty, Fei HuangFaye Feller, Aleksandra Rizo, Uwe Platzbecker

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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PURPOSE: Patients with lower-risk (LR) myelodysplastic syndromes (MDS) who are RBC transfusion dependent and have experienced relapse after or are refractory to erythropoiesis-stimulating agent (ESA) have limited treatment options. High telomerase activity and human telomerase reverse-transcription expression in clonal hematopoietic cells have been reported in patients with MDS. Imetelstat, a first-in-class competitive inhibitor of telomerase enzymatic activity, targets cells with active telomerase. We report efficacy, safety, and biomarker data for patients with LR MDS who are RBC transfusion dependent and who were relapsed/refractory to ESAs.

PATIENTS AND METHODS: In this two-part phase II/III study (MDS3001), the primary end point was 8-week RBC transfusion independence (TI) rate, with key secondary end points of 24-week RBC TI rate, TI duration, and hematologic improvement-erythroid.

RESULTS: Data from the phase II part of the study are reported. Of 57 patients enrolled and treated (overall population), 38 were non-del(5q) and hypomethylating agent and lenalidomide naïve (subset population). The 8- and 24-week RBC TI rates in the overall population were 37% and 23%, respectively, with a median TI duration of 65 weeks. In the subset population, 8- and 24-week RBC TI rates were 42% and 29%, respectively, with a median TI duration of 86 weeks. Eight-week TI rate was observed across all subgroups evaluated. Cytogenetic and mutational data revealed a reduction of the malignant clones, suggesting disease modification activity. The most common adverse events were cytopenias, typically reversible within 4 weeks.

CONCLUSION: Imetelstat treatment results in a meaningful, durable TI rate across a broad range of heavily transfused patients with LR MDS who are ineligible for or relapsed/refractory to ESAs. Biomarker analyses indicated effects on the mutant malignant clone.

Original languageEnglish
Pages (from-to)48-+
Number of pages11
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Issue number1
Early online date2020
Publication statusPublished - 1-Jan-2021


  • MDS

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