Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia

Amanda Breakey, Mercer University College of Pharmacy

According to the Myeloproliferative Neoplasm (MPN) Research Foundation, essential thrombocythemia (ET) is one of several chronic myeloproliferative neoplasms (MPNs). It is characterized by an increased number of platelets in the circulating blood and by a proliferation of platelet precursors in the bone marrow. While the most common complications include blood clotting and/or bleeding, it is noted that ET can lead to sometimes rare and serious complications, including myelofibrosis and acute leukemia.1

The Leukemia and Lymphoma Society states that while the cause of essential thrombocythemia is not fully understood, recent research has identified mutations in proteins that control signaling pathways in many patients with MPN. The literature states that about half of patients with ET have a mutation of the JAK2 (Janus kinase 2) gene; however, whether or not a patient has the mutation does not appear to significantly alter the nature or course of the disease.2  Additionally, the MPN Research Foundation states that about 23.5% of people with MPN and ET have a mutation called Calreticulin (CALR). While research is still ongoing, authors note that there are potential implications for the prognosis and treatment in individuals with the CALR mutation.1

According to The National Cancer Institute, current treatment options for ET include hydroxyurea, interferon-alpha or pegylated interferon-alpha, and anagrelide.3  A review in the journal Blood states that while current therapies induce nonspecific reductions in platelet counts, they do not have a tendency to eliminate or alter the biological characteristics of the disease.4

Title: Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia5
Design Phase II, open-label trial; N= 18
Objective Whether imetelstat could elicit hematologic and molecular responses in patients with essential thrombocythemia who had disease that was refractory to prior therapies or who had had unacceptable side-effects from previous therapies
Study Groups Initial dose of 7.5 mg/ kg of body weight group (n= 7) and initial dose of 9.4 mg/ kg of body weight group (n= 11)
Methods 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. In patients who achieved a response, the dose frequency was reduced to once every 2 weeks or less frequently.
Duration January 2010 through January 2013
Primary Outcome Measure Best overall hematologic response
Baseline Characteristics
Variable Patients (N= 18)
Age > 60 years- no. (%) 8 (44)
Males- no. (%) 8 (44)
Median time since initial diagnosis- yr. 7.2
Median platelet count- per mm3 788,000
Previous treatment- no (%)
Hydroxyurea 17 (94)
Anagrelide 13 (72)
Interferon 4 (22)
> 1 prior therapy 13 (72)
Resistant to ≥ 1 prior therapy- no. (%) 9 (50)
Unacceptable side effects from ≥ 1 prior therapy- no. (%) 14 (78)
Results The overall rate of hematologic response was 100% (95% confidence interval [CI], 83 to 100), and 16 of the 18 patients (89%) had a complete hematologic response (95% CI, 65 to 99).
Adverse Events Common Adverse Events: fatigue, nausea, diarrhea, headache, dizziness
Serious Adverse Events: neutropenia, headache, anemia, syncopal episode
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions Rapid and durable hematologic and molecular responses were observed in patients with essential thrombocythemia who received imetelstat.

Results of the study demonstrated that imetelstat induced a hematological response in 100% of patients diagnosed with essential thrombocythemia. This data suggests that use of a telomerase inhibitor such as imetelstat, may prove to be beneficial in the treatment of various hematologic myeloid malignancies. Additional research needs to be done to gain a better understanding of the mechanisms of action in the treatment of ET as well as long-term side effects.


  1. Essential Thrombocythemia (ET). Myeloproliferative Neoplasm (MPN) Research Foundation. Accessed September 4, 2015.
  2. Essential Thrombocythemia Facts. Leukemia & Lymphoma Society. Revised June 2012. Accessed September 4, 2015.
  3. Chronic Myeloproliferative Neoplasms Treatment–for health professionals. National Cancer Institute. Updated August 6, 2015. Accessed September 5, 2015.
  4. Beer PA, Erber WN, Campbell PJ, Green AR. How I treat essential thrombocythemia. Blood. 2011;117(5):1472-82.
  5. Baerlocher GM, Oppliger Leibundgut E, Ottmann OG, et al. Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia. N Engl J Med 2015;373:920-8. DOI: 10.1056/NEJMoa1503479.

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