Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia

The New England Journal of Medicine
Gabriela M BaerlocherDavid S Snyder

Abstract

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 mut...Continue Reading

References

Mar 23, 2005·Lancet·E Joanna BaxterUNKNOWN Cancer Genome Project
Jul 8, 2005·The New England Journal of Medicine·Claire N HarrisonUNKNOWN United Kingdom Medical Research Council Primary Thrombocythemia 1 Study
Oct 15, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Alfonso Quintás-CardamaSrdan Verstovsek
Jan 15, 2010·Recent Results in Cancer Research. Fortschritte Der Krebsforschung. Progrès Dans Les Recherches Sur Le Cancer·Alexander RöthGabriela M Baerlocher
Jan 6, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Tiziano BarbuiUNKNOWN European LeukemiaNet
Jul 13, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Tiziano BarbuiAyalew Tefferi
Dec 12, 2013·The New England Journal of Medicine·Thorsten KlampflRobert Kralovics
Dec 12, 2013·The New England Journal of Medicine·J NangaliaA R Green
Sep 4, 2015·The New England Journal of Medicine·Ayalew TefferiAnimesh Pardanani

❮ Previous
Next ❯

Citations

Oct 23, 2015·American Journal of Hematology·Ayalew Tefferi
Dec 25, 2015·The New England Journal of Medicine·Gabriela M BaerlocherDavid S Snyder
Sep 29, 2015·Current Hematologic Malignancy Reports·Naveen PemmarajuMichael A Thompson
Apr 28, 2016·Pharmacology & Therapeutics·Yinnan Chen, Yanmin Zhang
Jan 18, 2013·PloS One·Chatchawan SinghapolGabriele C Saretzki
Jun 25, 2016·Nature Reviews. Cancer·Greg M Arndt, Karen L MacKenzie
May 31, 2016·Genes·Yucheng Xu, Amir Goldkorn
Jul 11, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Karima Ait-AissaAndreas M Beyer
Aug 12, 2016·Hematological Oncology·Francesca PalandriMichele Baccarani
Aug 19, 2016·Genes·Theresa KreilmeierKlaus Holzmann
Sep 23, 2016·European Journal of Medicinal Chemistry·Philip A WaghornKatherine A Vallis
Sep 20, 2016·Journal of the American Chemical Society·Hyun-Jin KangLaurence H Hurley
Aug 27, 2016·Blood·Elisa Rumi, Mario Cazzola
Dec 29, 2016·Blood·Alessandro M Vannucchi, Claire N Harrison
Dec 17, 2016·Human Reproduction Update·D K HapangamaG Saretzki
Jul 5, 2017·Nature Reviews. Urology·Mindy Kim Graham, Alan Meeker
Nov 17, 2017·International Journal of Molecular Sciences·Theresa VaskoPatrick Ziegler
Mar 9, 2018·Expert Review of Hematology·Patrick M Harrington, Claire N Harrison
Feb 9, 2018·International Journal of Molecular Sciences·Takahiro EitsukaTeruo Miyazawa
Dec 15, 2017·Nucleic Acids Research·Xiulong Shen, David R Corey
Oct 28, 2017·Blood·Guido Finazzi
Nov 3, 2017·Therapeutic Advances in Hematology·Ashwin Kishtagari, Justin Watts
Jul 26, 2017·Liver International : Official Journal of the International Association for the Study of the Liver·Raquel M Alves-PaivaRodrigo T Calado
Apr 14, 2018·Blood·Francesco Passamonti, Margherita Maffioli
Jul 12, 2018·AJR. American Journal of Roentgenology·Ailbhe C O'NeillNikhil H Ramaiya
Feb 23, 2019·Expert Review of Hematology·Barbara Mora, Francesco Passamonti
Apr 24, 2019·Cell Biochemistry and Function·Karollyne da Silva MoraisDiêgo Madureira de Oliveira
May 6, 2019·Expert Opinion on Emerging Drugs·Lucia Masarova, Srdan Verstovsek
Dec 1, 2017·Nature Reviews. Gastroenterology & Hepatology·Nina FreyMichael Bitzer
Sep 14, 2019·Therapeutic Advances in Hematology·Prithviraj Bose, Srdan Verstovsek
Jan 7, 2020·Current Topics in Medicinal Chemistry·Xiaotian YuanDawei Xu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.