Fludarabine, cyclophosphamide, mitoxantrone plus rituximab (FCM-R) in frontline CLL <70 Years.

Randomized trials demonstrated the superiority of chemoimmunotherapy over chemotherapy in the frontline treatment of CLL. Based on favorable experience with the addition of mitoxantrone (M) to fludarabine (F) plus cyclophosphamide (C), we designed a pilot study testing the combination of FCM plus rituximab (R). Thirty patients with previously untreated, symptomatic CLL, <70 years, and beta-2-microglobulin <twice upper limit of normal were evaluated. Treatment consisted of F 25mg/m(2)/day on days 2-4, C 250 mg/m(2)/day on days 2-4, M 6 mg/m(2) on day 2, and R 375 mg/m(2) on day 1. For cycles 2-6, FCM started day 1 together with R 500 mg/m(2). Pegfilgrastim was administered with each cycle. Cycles were repeated every 4-6 weeks. Complete remission (CR) was achieved in 83% of 30 patients, nodular partial response in 10%, and partial response in 3%. The overall response rate was 96%. Sixteen of 24 CR patients (67%) achieved a flow cytometry response with <1% marrow CD5/CD19-positive cells and 13 of 21 CR patients (62%) were MRD-negative by molecular evaluation for clonal IgV(H). With a median follow up of 38.5 months, the median time to treatment failure (TTF) has not been reached. A comparison with a historical group of FCR-treated patients showed no significant differences with respect to response and toxicities. FCM-R is highly active in patients < 70 years with favorable beta-2-microglobulin levels and previously untreated CLL. Outcome does not differ from FCR-treated patients. Copyright (c) 2009 Elsevier Ltd. All rights reserved.