Treatment with anagrelide was associated with prolonged responses in patients with essential thrombocythemia (ET), according to results of a long-term observational, retrospective study reported in the British Journal of Haematology.
Anagrelide is an oral imidazo-quinazoline compound that was approved in 1997 by the US Food and Drug Administration (FDA) to reduce platelet levels and reduce the risk of thrombosis in patients with thrombocythemia secondary to myeloproliferative disorders. This drug was also licensed by the European Medicines Agency (EMA) in 2004 to treat patients with ET, a Philadelphia chromosome-negative myeloproliferative neoplasm, who are not responding to or unable to tolerate current treatment, as well as those considered to be at high risk due to age, platelet count, or history of thrombosis.
The primary objective of this study was to evaluate real-world use of anagrelide over the last 25 years in patients with ET who were followed in the Haematological Institutes of the Italian Latium region.
Of the 938 patients included in the Latium Group with ET diagnosed between January 1981 and January 2012, 150 of those patients were treated with anagrelide and included in this analysis. The percentages of patients initiating anagrelide before and after EMA licensing were 37.3% and 62.7%, respectively. Median follow-up for these patients was 12.5 years.
Some of the key findings of this study included the following:
- Median age at ET diagnosis in the study population was 42.7 years with a median age at initiation of anagrelide of 45.9 years, demonstrating its clinical use in a younger population of patients with ET.
- Anagrelide was used as a first-, second-, or third-line treatment in 34.7%, 52%, and 13.3% of patients, respectively.
- In cases where anagrelide was not used in the first-line setting, the drugs most commonly used immediately prior to the switch to anagrelide were hydroxycarbamide (54.1%), recombinant interferon-alpha (22.4%), and hydroxycarbamide plus recombinant interferon-alpha (13.3%).
- Patients underwent treatment with anagrelide for a median of 7.4 years, with 38.2% and 47.2% of evaluable patients achieving a complete response or partial response, respectively.
- Maintenance of response for more than 50% of the treatment period was observed in 38.5% and 57.3% of evaluable patients with a platelet count less than 400 × 109/L and between 400 and 600 × 109/L, respectively.
- Although no adverse effects of anagrelide were reported for half of patients, palpitations, peripheral vasodilation, anemia, diarrhea, and gastric distress were reported for 81%, 18%, 15%, 7.4%, and 7.4% of the remaining patients.
- Thrombotic events occurred in 9.5% of evaluable patients treated with anagrelide with 6.8% and 2.7% of patients experiencing an arterial or venous thrombotic event, respectively.
- Secondary myelofibrosis was diagnosed in 10.6% of evaluable patients at a median age of 55.6 years, with median times from ET diagnosis and start of anagrelide to diagnosis of secondary myelofibrosis of 9.1 and 5.7 years, respectively.
- Acute myeloid leukemia (AML) was diagnosed in 2% of evaluable patients at a median age of 70.5 years, with median times from ET diagnosis and start of anagrelide to AML diagnosis of 11.2 years and 2.9 years, respectively
The study authors noted an apparent suitability of anagrelide for younger patients with ET and emphasized the importance of thrombotic risk assessment and monitoring of cardiac function in all patients with ET treated with anagrelide.
1. Mazzucconi MG, Baldacci E, Latagliata R, et al. Anagrelide in essential thrombocythemia (ET): results from 150 patients over 25 Years by the ‘Ph1-negative Myeloproliferative Neoplasms Latium Group [published online May 22, 2020]. Eur J Haematol. doi: 10.1111/ejh.13454
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