Background and objectives: Fludarabine is an effective therapy for patients with chronic lymphocytic leukemia (CLL) and interferon-alpha (IFN-alpha) has been reported to have anti-leukemic activity in CLL patients. A randomized study was designed to evaluate whether the addition of IFN-alpha to a first-line treatment with fludarabine and prednisone could increase the response rate in patients with advanced CLL and whether IFN-alpha given as maintenance therapy could improve the duration of response.
Design and methods: One hundred and thirty-three patients were randomized to receive fludarabine (25 mg/m2/i.v., days 9-13) and prednisone (20 mg/m2, days 1, 3, 5, 7 and 14 and 40 mg/m2, days 9-13) (arm A: 66 patients) or in addition to the same schedule, IFN-alpha (2 MUI/sc, days 1, 3, 5, 7, 9, 11, 13 and 15) (arm B: 67 patients). Seventy-eight patients responsive to therapy entered the post-remission phase of the study in which 41 patients were randomized to receive IFN-alpha (3 MUI three times a week) and 37 to clinical observation.
Results: A similar response rate (complete responses + partial responses) was observed in the 2 arms: 86% for arm A and 84% for arm B (p = 0.4). A longer response duration was observed in patients who achieved a complete response (p = 0.001) and in patients who received maintenance therapy with IFN-alpha (p < 0.05). However, the quality of response was the only significant and independent factor influencing response duration (p < 0.01). No benefits in terms of infection-related mortality and morbidity could be ascribed to IFN-alpha administration.
Interpretation and conclusions: In previously untreated CLL patients with advanced disease a high response rate is obtained from first-line fludarabine and prednisone and no benefit is derived from the addition of IFN-alpha to this regimen. The achievement of a good quality response to therapy was the only independent predictor of a prolonged response.