Abstract

Background:Anagrelide is licensed in Austria for first line treatment of patients with high risk essential thrombocythemia (ET). A recently published, large prospective long‐term observational study revealed, that anagrelide is mainly used for treatment of younger patients and only rarely in patients above 60 years of age (Birgegard et al, Haematologica 2018). However, data on efficacy and safety of anagrelide in older patients are lacking.Aims:The aim of the study was to assess safety and efficacy of treatment with anagrelide in older patients by retrospectively analyzing a large registry of patients with thrombocythemic myeloproliferative neoplasms (MPN).Methods:All patients of the registry were considered who exhibited a valid diagnosis of ET and at least one follow up investigation. Registry entry was the start of treatment with anagrelide. Concurrent treatment with aspirin and other cytoreductive treatment when indicated were at the discretion of the treating physician.Efficacy and safety of treatment with anagrelide in older patients (cut‐off 65 and 75 years, respectively) versus younger patients was investigated. For efficacy analysis the platelets cut off 574.5 G/L (Buxhofer‐Ausch et al, EJH 2016) was applied beside the traditional cut off (400 G/L). Subgroup comparisons were performed by analyses of covariance (with observation time and dosage of Anagrelide as covariates) and by log rank tests (because of clear group differences in observation time).Results:570 Patients, of which 68% were females, fulfilled all inclusion criteria. Patients’ age at time of study entry was median 61 [18.25; 90.75] years. Older patients received on average a lower dosage of anagrelide than younger patients. Median follow up was 2.98 [1.09;5.56] years. By setting the age cut off at 65 years, anagrelide proved more effective in patients above 65 years regarding lowering the platelet count below 400G/L (p = 0.001) and equally effective when the cut off 574,7 G/L was applied (p = 0.278). There was no difference between age groups in occurrence of a major thrombotic event. However, time to dizziness (p = 0.018) and time to impaired renal function (p = 0.001) analyses showed better results for patients below 65 years. When considering a cut‐ off of 75 years there was no difference in regards of platelets lowering below 400 G/L (p = 0.955) as well as below 574.5 G/L (p = 0.480). The statistical comparison exhibited a difference in the time to a major thrombotic event in favor of patients below 75 years of age (p = 0.032). Also time to headache (p = 0.031), time to anemia (p = 0.032) and time to renal impairment (p < 0.002) analyses show markedly better results for patients on anagrelide below 75 years.Summary/Conclusion:Treatment with anagrelide exhibits an excellent efficacy, especially when considering the platelet cut off 574.7 G/L, in all age groups at start of treatment with a good safety profile. Thus, Anagrelide is a valid treatment option also for older patients with thrombocythemic myeloproliferative neoplasms.

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