PEG Interferon a-2b (PEG-Intron) in Essential Thrombocythemia: Phase II Study for Determination of the Minimum Effective, Safe and Tolerated Dose. Preliminary Data.

In Essential Thrombocythemia (ET) various subsets of patients are satisfactorily treated with Interferons (IFN) alpha (Blood 1996; 87 suppl 1, 581a). Since long-lasting treatment is usually required, the patient compliance is difficult to be maintained mainly because frequent subcutaneous injections are necessary. On the basis of the optimized pharmacokinetics of the new pegilated IFNs alpha weekly administered, a phase II study was designed to determine the minimum effective, safe and tolerated dose of PEG Interferon alpha-2b (PEG-Intron, Schering-Plough) in a cohort of ET patients. The major endpoint of this study, with a sample size of 86 cases, is to evaluate if at the end of the first year of treatment at least 45% of patients reaches the Hematological Response (HR = platelet count < 500 x 109/L). In detail, the starting PEG-Intron dose of 25 ug/week is scheduled to be increased to 50, 75 and 100 ug/week if the HR was not obtained at weeks 13, 26 and 39 respectively. Since december 2000, in 16 Hematological Institutions of the Gruppo Italiano Malattie Mieloproliferative Croniche (GIMMC) the PEG-Intron treatment has been started in 77 pts, 26 M and 51 F, median age 46 yrs (range 18-72). At the baseline patients showed: age > 60 yrs (n=12), platelet count > 1000 x 109/L (n=65), previous thrombosis (n=5), peripheral granulocyte precursors (n=7), moderate splenomegaly (n=18), mean platelet count 1112 x109/L, mean Hb level 13.4 g/dl, mean WBC count 9.2 x109/L. Preliminary data of the platelet decrease are shown in the table: week cases platelets Hematological (x109/L) Response** mean % cases % 0 77 1112 100 / / 4 64 831 77 4 6 13 30* 700 64 2 7 18 21 594 52 9 42 22 10 580 47 4 40 * at week 13, 28/30 patients increased PEG-Intron dose (50ug/week) ** platelet count < 500 x 109/LInterestingly, after week 18 the mean platelet count was half of the baseline value and 40% of the patients showed a platelet count < 500 x 109/L. Notably, no WHO grade III or IV toxicity was observed and only one patient decided to withdraw from the study at week 6 due to WHO grade I orticaria. These preliminary data suggest that PEG-Intron, also at low dose, is able in ET patients to significantly decrease the platelet count with a negligible toxicity.