Abstract
Essential thrombocythemia (ET) is a myeloproliferative disorder (MPD) associated with thrombohemorrhagic complications. The disease uncommonly progresses to myelofibrosis or acute leukemia; the risk of transformation may be increased by cytoreductive treatments. Anagrelide (Xagrid®/Agrylin®) is a non-cytotoxic agent that selectively reduces platelet production. A retrospective analysis of an open-label, multi-center trial including MPD patients treated by long-term anagrelide was performed.1 The total safety population comprised 3660 MPD patients (2251 with ET) with a maximum follow-up of 11.4 years. Prior myelosuppressive therapy had been administered in 81% of patients; 33% of these patients were changed to anagrelide because of previous toxicity and 31% because of poor platelet control. Efficacy and safety data hereafter are described for the ET population. There were 934 ET efficacy evaluable patients: with a response seen in 78.7% of them (complete and partial response: 67.2% and 11.5%, respectively). This was similar to that of patients who failed previous therapy (78.8%) or were intolerant (75.6%). After the first year, platelet count decreases were well maintained. Results were similar for both sexes, different age groupings and ethnic origins. AEs occurred in 40.2% of the patients and were generally mild. Anagrelide was discontinued in 38.6% of patients (adverse events accounting for 29.2% of patients stopping treatment). At baseline, 163/934 (17.5%) patients reported ET-related symptoms including GI and other bleedings, arterial or venous thrombosis, angina, pulmonary embolism, transient ischemic attacks, peripheral ischemia and paresthesia. This had reduced to 7.9% (63/796, P<0.001) after 12 weeks and was maintained during follow up (4.3%: 15/470 at 1 year, 3.2%: 6/239 at 2 years, P<0.001.2 Transformation to AML/MDS occurred in 47/2251 (2.1%), but only in subjects who had previously been exposed to cytoreductive treatment. Mortality rate in the safety population was as to be expected in ET patients: 8.8%. Most common reason for death (> or =1%) were CML, reason unknown or unspecified and sepsis. Anagrelide (Xagrid®/Agrylin®) effectively reduces platelet counts and thrombohemorrhagic complications in patients with ET. This is independent of gender, age, ethnic origin and prior therapy. The drug demonstrates a recognized safety profile. Benefits are maintained during long-term follow-up without an increase in disease transformation.
