Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Telomerase inhibitor imetelstat in patients with essential thrombocythemia

Baerlocher, Gabriela M., Oppliger Leibundgut, Elisabeth, Ottmann, Oliver, Spitzer, Gary, Odenike, Olatoyosi, McDevitt, Michael A., Röth, Alexander, Daskalakis, Michael, Burington, Bart, Stuart, Monic and Snyder, David S. 2015. Telomerase inhibitor imetelstat in patients with essential thrombocythemia. New England Journal of Medicine 373 (10) , pp. 920-928. 10.1056/NEJMoa1503479

Full text not available from this repository.

Abstract

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS Rapid and durable hematologic and molecular responses were observed in patients with essential thrombocythemia who received imetelstat.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Massachusetts Medical Society
ISSN: 0028-4793
Last Modified: 04 Jun 2017 08:49
URI: http://orca.cf.ac.uk/id/eprint/85661

Citation Data

Cited 73 times in Scopus. View in Scopus. Powered By Scopus® Data

Cited 9 times in Web of Science. View in Web of Science.

Actions (repository staff only)

Edit Item Edit Item