Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia.

Baerlocher, Gabriela M.; Oppliger Leibundgut, Elisabeth; Ottmann, Oliver G; Spitzer, Gary; Odenike, Olatoyosi; McDevitt, Michael A; Röth, Alexander; Daskalakis, Michael; Burington, Bart; Stuart, Monic; Snyder, David S (2015). Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia. New England journal of medicine NEJM, 373(10), pp. 920-928. Massachusetts Medical Society MMS 10.1056/NEJMoa1503479

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Imetelstat, a 13-mer oligonucleotide that is covalently modified with lipid extensions, competitively inhibits telomerase enzymatic activity. It has been shown to inhibit megakaryocytic proliferation in vitro in cells obtained from patients with essential thrombocythemia. In this phase 2 study, we investigated whether imetelstat could elicit hematologic and molecular responses in patients with essential thrombocythemia who had not had a response to or who had had unacceptable side effects from prior therapies.


A total of 18 patients in two sequential cohorts received an initial dose of 7.5 or 9.4 mg of imetelstat per kilogram of body weight intravenously once a week until attainment of a platelet count of approximately 250,000 to 300,000 per cubic millimeter. The primary end point was the best hematologic response.


Imetelstat induced hematologic responses in all 18 patients, and 16 patients (89%) had a complete hematologic response. At the time of the primary analysis, 10 patients were still receiving treatment, with a median follow-up of 17 months (range, 7 to 32 [ongoing]). Molecular responses were seen in 7 of 8 patients who were positive for the JAK2 V617F mutation (88%; 95% confidence interval, 47 to 100). CALR and MPL mutant allele burdens were also reduced by 15 to 66%. The most common adverse events during treatment were mild to moderate in severity; neutropenia of grade 3 or higher occurred in 4 of the 18 patients (22%) and anemia, headache, and syncope of grade 3 or higher each occurred in 2 patients (11%). All the patients had at least one abnormal liver-function value; all persistent elevations were grade 1 or 2 in severity.


Rapid and durable hematologic and molecular responses were observed in patients with essential thrombocythemia who received imetelstat. (Funded by Geron; number, NCT01243073.).

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)

UniBE Contributor:

Baerlocher, Gabriela M., Oppliger Leibundgut, Elisabeth, Daskalakis, Michael


600 Technology > 610 Medicine & health




Massachusetts Medical Society MMS




Verena Zwahlen

Date Deposited:

24 Mar 2016 14:09

Last Modified:

05 Dec 2022 14:53

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