Telomerase Inhibitor Imetelstat in Essential Thrombocythemia and Myelofibrosis.

To the Editor: Baerlocher et al. (Sept. 3 issue)1 report on telomere-targeted treatment with imetelstat in 18 patients with essential thrombocythemia. The drug was effective in controlling platelet levels in all patients, albeit often at the expense of hemoglobin and neutrophil levels. However, the other main treatment goals in essential thrombocythemia2 — controlling symptoms and preventing both disease progression and thromboembolic complications — were definitely not achieved. Fatigue, diarrhea, and nausea were all reported by more than 70% of the patients. A total of 3 patients had progression to myelofibrosis, and 2 patients had a thromboembolic event. Thus, treatment with imetelstat does not seem to be promising in this relatively benign disease. Only 4 patients had received interferon before undergoing this experimental therapy. Pegylated interferon alfa-2 is effective in controlling thrombocytosis in most patients, and it is not associated with myelofibrotic transformation, leukemogenicity, or other adverse long-term events.3 Furthermore, interferon may induce a deep molecular remission (i.e., a very low JAK2 V617F mutation level) and normalization of bone marrow changes, effects that in some patients may be maintained years after treatment cessation.3,4 In Denmark, interferon is suggested as first-line treatment in patients with essential thrombocythemia.5