It may be time for clinicians to re-evaluate the use of anagrelide in patients with high-risk essential thrombocythemia (ET), according to a study published in the American Journal of Hematology.
Researchers conducted a retrospective review and discovered significantly decreased overall survival (OS) and myelofibrosis-free survival (MFFS) in patients with ET diagnosed after the FDA approval of anagrelide. While the study is unable to definitively link anagrelide to the worsening of OS and MFFS over time, it does raise a number of concerns.
The researchers examined the potential impact of anagrelide therapy on survival and disease complications in 1076 patients (median age 58 years) with ET. The researchers found that after the 1997 FDA approval of anagrelide, there was a significant difference in OS (P =.006; hazard ratio [HR] 1.4) and MFFS (P <.001; HR 4.2) in favor of patients diagnosed prior to 1997. This observed difference was sustained during multivariable analysis that included both sex and the international prognostic score for ET (IPSET). Similarly stratified survival data in 665 patients with polycythemia vera and 1282 patients with primary myelofibrosis demonstrated no similar impact on OS.
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The difference in OS in this study was most pronounced after the first decade of diagnosis, with 10-year survival rates at 75% and 20-year survival rates at 50% for diagnosis prior to 1997 compared to 72% at 10 years and 21% at 20 years for patients diagnosed between 1997 and 2017. The 10-year risk of fibrotic progression was 3% and the 20-year risk was 15% for diagnosis prior to 1997. However, that increased to 14% at 10 years and 46% at 20 years for diagnosis after 1997.
The side effects of anagrelide, which is an oral imidazoquinoline derivative that inhibits platelet aggregation, include headaches, palpitations, anemia, serious cardiac arrhythmias, cardiomyopathy, and renal insufficiency, noted the authors.
The authors concluded, “Whether or not anagrelide therapy was to blame for the worsening of OS and MFFS over time, observed in the current study, cannot be assumed and requires validation in a prospective study.”
Reference
1. Tefferi A, Szuber N, Vallapureddy RR, et al. Decreased survival and increased rate of fibrotic progression in essential thrombocythemia chronicled after the FDA approval date of anagrelide, [published online September 25, 2018]. doi: 10.1002/ajh.25294
