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

Michael J. Keating*, Susan O'Brien, Maher Albitar, Susan Lerner, William Plunkett, Francis Giles, Michael Andreeff, Jorge Cortes, Stefan Faderl, Deborah Thomas, Charles Koller, William Wierda, Michelle A. Detry, Alice Lynn, Hagop Kantarjian

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

833 Scopus citations

Abstract

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% CI, 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% CI, 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% CI, 57% to 81%).

Original languageEnglish (US)
Pages (from-to)4079-4088
Number of pages10
JournalJournal of Clinical Oncology
Volume23
Issue number18
DOIs
StatePublished - 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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