Outcome of advanced chronic lymphocytic leukemia following different first-line and relapse therapies: a meta-analysis of five prospective trials by the German CLL Study Group (GCLLSG)
Paula Cramer,
Susanne Isfort,
Jasmin Bahlo,
Stephan Stilgenbauer,
Hartmut Döhner,
Manuela Bergmann,
Martina Stauch,
Michael Kneba,
Elisabeth Lange,
Petra Langerbeins,
Natali Pflug,
Gabor Kovacs,
Valentin Goede,
Anna-Maria Fink,
Thomas Elter,
Kirsten Fischer,
Clemens-Martin Wendtner,
Michael Hallek,
Barbara Eichhorst
Affiliations
Paula Cramer
Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany
Susanne Isfort
Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany;Department for Oncology, Hematology and Stem Cell Transplantation, University Hospital Aachen, Munich, Germany
Jasmin Bahlo
Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany
Stephan Stilgenbauer
Department III of Internal Medicine, University Hospital Ulm, Munich, Germany
Hartmut Döhner
Department III of Internal Medicine, University Hospital Ulm, Munich, Germany
Manuela Bergmann
Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine, Hospital Munich-Schwabing, Munich, Germany
Martina Stauch
Specialized Practice for Hematology and Oncology and Day Hospital, Kronach, Germany
Michael Kneba
Department II of Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Germany
Elisabeth Lange
Protestant Hospital Hamm, Clinic for Hematology, Oncology and Palliative Care, Hamm, Germany
Petra Langerbeins
Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany
Natali Pflug
Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany
Gabor Kovacs
Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany
Valentin Goede
Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany
Anna-Maria Fink
Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany
Thomas Elter
Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany
Kirsten Fischer
Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany
Clemens-Martin Wendtner
Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany;Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine, Hospital Munich-Schwabing, Munich, Germany
Michael Hallek
Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany
Barbara Eichhorst
Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, University of Cologne, Munich, Germany
To evaluate the effect of first-line and subsequent therapies, the outcome of 1,558 patients with chronic lymphocytic leukemia from five prospective phase II/III trials conducted between 1999 and 2010 was analyzed. The 3-year overall survival rate was higher after first-line treatment with chemoimmunotherapies such as fludarabine/cyclophosphamide/rituximab (87.9%) or bendamustine/rituximab (90.7%) compared to chemotherapies without an antibody (fludarabine/cyclophosphamide: 84.6%; fludarabine: 77.5%; chlorambucil: 77.4%). Furthermore, the median overall survival was longer in patients receiving at least one antibody-containing regimen in any treatment line (94.4 months) compared to the survival in patients who never received an antibody (84.3 months, P24 months after first-line therapy repeated the first-line regimen. Among 315 patients requiring treatment ≤24 months after first-line therapy, cyclophosphamide/doxorubicin/vincristine/prednisone with or without rituximab as well as alemtuzumab were the most commonly used therapies. In these early relapsing patients, the median overall survival was shorter following therapies containing an anthracycline and/or three or more cytotoxic agents (e.g. cyclophosphamide/doxorubicin/vincristine/prednisone or fludarabine/cyclophosphamide/mitoxantrone, 30.0 months) compared to single agent chemotherapy (e.g. fludarabine; 39.6 months) and standard chemoimmunotherapy (e.g. fludarabine/cyclophosphamide/rituximab: 61.6 months). In conclusion, the analysis confirms the superior efficacy of chemoimmunotherapies in patients with chronic lymphocytic leukemia. Moreover, the use of aggressive chemo(immuno)therapy combinations in patients with an early relapse does not offer any benefit when compared to less intensive therapies. Trial identifier: NCT00281918, ISRCTN75653261, ISRCTN36294212, NCT00274989 and NCT00147901.
