Essential Thrombocythemia: A Prospective Analysis of Efficacy and Safety of Anagrelide for Long Term Treatment in Patients Below and Above the Age of 60 Years.
Authors: Gisslinger Heinz 
Published: April 2020

Thromboembolic complications and less frequently bleeding characterize morbidity and mortality in patients with essential thrombocythemia (ET). The average estimated risk for thrombotic episodes in ET is 6.6% per patient year and platelet counts above 1000G/L, older age (&gt;60 years) and a history of thrombosis were identified as major risk factors for serious complications. Since a direct correlation of platelet numbers with the number of thrombotic events is suggested by numerous prospective trials, it is generally accepted that these patients should receive platelet lowering treatment. Although hydroxyurea is considered as the treatment of choice in ET, there is still major concern about leukemogenicity of this compound. Anagrelide, on the other hand seems to be better tolerated in younger patients, but this has not been proved by prospective studies. It is therefore the aim of the present study to compare tolerability and efficacy of anagrelide (Thromboreductin, a novel non-immediate release formulation of anagrelide) over a prolonged time between ET patients below the age of 60 years with those above the age of 60 years. Among a total of 722 patients with ET on anagrelide who were prospectively documented within a standardized patient registry, 386 patients were previously untreated at the time of initiation of anagrelide therapy and this therapy was prospectively documented up to 5 years. The median age of this previously untrated patient cohort was 58 years (6 to 91 years), 179 (46,4%) patients were older than 60 years and 274 (71%) patients were female. Sixtythree patients (16,3%) had a history of thrombosis. The main inclusion criteria were those defined for qualifying a patient to be at high risk. During the first two years of follow up, the group of younger patients (&lt; 60 years) did receive higher daily doses of anagrelide as compared to the older patient cohort (2,0mg vs.1,5mg). Anagrelide reduced platelet counts from a median baseline value of 920G/L to 581G/L and 382 G/L on month 3 and month 60 respectively. The overall response rate (platelet counts&lt; 600G/L) was 64%. The rate of complete response (platelet counts &lt;450G/L) went up from 58% after one year to 71% after 5 years of treatment. Group comparisons showed that a significant response to anagrelide was achieveable in patients below and above the age of 60 years with no significant difference between the two groups. With regard to safety, there is no evidence that anagrelide gives concern to an increased rate of bleeding (2%) or disease progression. Over the 5 year follow up period an adverse event was recorded in 24% of patients. The rate of treatment discontinuation as a result of adverse events was low (5%), treatment was discontinued when no further response was achieved or a negative risk benefit judgement of the treating physician was made. Only 4 patients of the whole cohort discontinued anagrelide due to disease progression. A small number of patients (12/722), 1,7%) died during the 5 years observation period, all cases were described as not drug related. In summary the data confirm that anagrelide yields comparable response rates in the two age groups during long term treatment.