PEG-IFN-α-2b therapy in BCR-ABL-negative myeloproliferative disorders: Final result of a phase 2 study

BACKGROUND. Interferon-alpha (IFN-α) has shown significant activity in the treatment of BCR-ABL-negative myeloproliferative disorders (MPDs), particularly essential thrombocythemia (ET) and polycythemia vera (PV). PEG-IFN-α-2b is a pegylated IFN-α-2b with a significant advantage over nonpegylated form in that it is administered once a week. METHODS. Thirty-eight patients with BCR-ABL-negative MPDs were treated with PEG-IFN-α-2b, given subcutaneously weekly, at the starting dose of 3 μg/kg/wk for the first 14 patients and then 2 μg/kg/wk for the next 24 patients, with intent to treat patients as long as they benefited from the therapy. RESULTS. Median age was 54 years. Patient diagnoses were: 13 (34%) ET; 11 (29%) primary myelofibrosis (PMF); 5 (13%) BCR-ABL-negative chronic myeloid leukemia (CML); 4 (10.5%) hypereosinophilic syndrome (HES); 4 (10.5%) PV; and 1 (3%) unclassified myeloproliferative disease (uMPD). Recorded grade 3-4 toxicities were related to fatigue, myelosuppression, and musculoskeletal pain. Ten (26%) patients stopped treatment because of toxicity. Thirteen (34%) patients achieved a complete remission, and 4 (11%) achieved a partial response. Only 1 patient with PMF responded. Median time to response was 5 months. Median duration of response was 20 months. Three patients had a sustained response for >24 months. CONCLUSIONS. PEG-IFN-α-2b, with proper dose modifications, is effective in controlling disease in a significant proportion of BCR-ABL-negative MPD patients, particularly ET and PV However, toxicities encountered with PEG-IFN-α-2b therapy are similar to those obtained with conventional IFN-α, thus limiting the duration of therapy.