PEG Intron in Essential Thrombocythemia: Two Years Treatment in 90 Patients.

In Essential Thrombocythemia (ET) the optimized pharmacokinetics of the weekly-administered pegilated Interferons a (IFN) may increase the patient compliance to a long-lasting IFN treatment. This phase II study has been designed to evaluate in ET patients efficacy, safety and tolerability of a two years treatment with PEG Interferon a - 2b (PEG Intron, Schering-Plough). In 16 Hematological Institutions of the Gruppo Italiano Malattie Mieloproliferative Croniche (GIMMC) the PEG Intron treatment has been started in 90 ET patients, 30 Males and 60 Females, median age 45 years (18-72), previously treated with Alkylating agents (14%), Hydroxyurea (64%), IFN a (31%), Anagrelide (7%) and Antiplatelet drugs (91%). The patients showed: age over 60 (19%), previous thrombosis (4%), disease related symptoms (40%), thrombotic general risk factors (57%), platelet count > 1000 x109/L (81%), peripheral granulocyte precursors (8%), splenomegaly (22%), mean platelet count 1093 x 109/L. In the first year (Part I of the study) the very low initial dose of PEG Intron (25 mg/week) was increased to 50, 75 and 100 mg/week in the patients not reaching the Hematological Response (HR=PLT <500 x109/L) at weeks 13, 26 and 39, respectively. The HR was obtained in 17%, 55%, 79% and 79% of cases after 13, 26, 39 and 52 weeks of treatment, respectively. The PEG Intron toxicity, never of WHO grade IV and only in two cases of grade III, was cause of dose reduction, transitory interruption and drug withdrawal in 7%, 17% and 7% of cases, respectively. Ten patients showed laboratory signs of thyroid dysfunction. Neither thrombotic nor hemorrhagic events were observed. In the second year (Part 2 of the study) 76 responding patients continued PEG Intron treatment at progressively decreasing dose in order to maintain the HR. In detail, the mean PEG Intron dose (mg/week) from the baseline level of 52 was reduced to the values of 33, 34, 30 and 29 at weeks 13, 26, 39 and 52, respectively. In the patients still on PEG Intron treatment at weeks 13, 26, 39 and 52 the rate of the HR was 94.2%, 83.2%, 81.5% and 84.9%, respectively. A withdrawal of PEG Intron was registered after 8-44 weeks (median 23.5) in 10 patients, in 8 of them as consequence of drug related toxicity. The reduction of the PEG Intron dose allowed at week 52 to a significant decrease of the toxicity, respect the baseline. These preliminary data show that PEG Intron at relatively low dose is able to induce and to maintain the HR in the majority of ET patients, with acceptable safety and toxicity.