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

Research output: Contribution to journalArticle

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 - Dec 1 2005
Externally publishedYes

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B-Cell Chronic Lymphocytic Leukemia
Cyclophosphamide
Flow Cytometry
Therapeutics
Fever of Unknown Origin
fludarabine
Rituximab
Infection
Neutropenia
Treatment Failure
Bone Marrow Cells
Lymphoma
Monoclonal Antibodies
Safety
Cell Line

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. / Keating, Michael J.; O'Brien, Susan; Albitar, Maher; Lerner, Susan; Plunkett, William; Giles, Francis; Andreeff, Michael; Cortes, Jorge; Faderl, Stefan; Thomas, Deborah; Koller, Charles; Wierda, William; Detry, Michelle A.; Lynn, Alice; Kantarjian, Hagop.

In: Journal of Clinical Oncology, Vol. 23, No. 18, 01.12.2005, p. 4079-4088.

Research output: Contribution to journalArticle

Keating, MJ, O'Brien, S, Albitar, M, Lerner, S, Plunkett, W, Giles, F, Andreeff, M, Cortes, J, Faderl, S, Thomas, D, Koller, C, Wierda, W, Detry, MA, Lynn, A & Kantarjian, H 2005, 'Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia', Journal of Clinical Oncology, vol. 23, no. 18, pp. 4079-4088. https://doi.org/10.1200/JCO.2005.12.051
Keating, Michael J. ; O'Brien, Susan ; Albitar, Maher ; Lerner, Susan ; Plunkett, William ; Giles, Francis ; Andreeff, Michael ; Cortes, Jorge ; Faderl, Stefan ; Thomas, Deborah ; Koller, Charles ; Wierda, William ; Detry, Michelle A. ; Lynn, Alice ; Kantarjian, Hagop. / Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. In: Journal of Clinical Oncology. 2005 ; Vol. 23, No. 18. pp. 4079-4088.
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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{\%}).",
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T1 - Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia

AU - Keating, Michael J.

AU - O'Brien, Susan

AU - Albitar, Maher

AU - Lerner, Susan

AU - Plunkett, William

AU - Giles, Francis

AU - Andreeff, Michael

AU - Cortes, Jorge

AU - Faderl, Stefan

AU - Thomas, Deborah

AU - Koller, Charles

AU - Wierda, William

AU - Detry, Michelle A.

AU - Lynn, Alice

AU - Kantarjian, Hagop

PY - 2005/12/1

Y1 - 2005/12/1

N2 - 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%).

AB - 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%).

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