Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia

Purpose Fludarabine and cyclophosphamide (FC), which are active in treatment of chronic lymphocytic leukemia (CLL), are synergistic with the monoclonal antibody rituximab in vitro in lymphoma cell lines. A chemoimmunotherapy program consisting of fludarabine, cyclophosphamide, and rituximab (FCR) was developed with the goal of increasing the complete remission (CR) rate in previously untreated CLL patients to >= 50 %. Patients and Methods We conducted a single-arm study of FCR as initial therapy in 224 patients with progressive or advanced CLL. Flow cytometry was used to measure residual disease. Results and safety were compared with a previous regimen using FC. Results The median age was 58 years; 75 patients (33 %) had Rai stage III to IV disease. The CR rate was 70 % (95 % Cl, 63 % to 76 %), the nodular partial remission rate was 10 %, and the partial remission rate was 15 %, for an overall response rate of 95 % (95 % Cl, 92 % to 98 %). Two thirds of patients evaluated with flow cytometry had less than 1 % CD5- and CD19-coexpressing cells in bone marrow after therapy. Grade 3 to 4 neutropenia occurred during 52 % of courses; major and minor infections were seen in 2.6 % and 10 % of courses, respectively. One third of the 224 patients had >= one episode of infection, and 10 % had a fever of unknown origin. Conclusion FCR produced a high CR rate in previously untreated CLL. Most patients had no detectable disease on flow cytometry at the end of therapy. Time to treatment failure analysis showed that 69 % of patients were projected to be failure free at 4 years (95 % Cl, 57 % to 81 %).