Cramer, Paula, Isfort, Susanne, Bahlo, Jasmin, Stilgenbauer, Stephan, Doehner, Hartmut, Bergmann, Manuela, Stauch, Martina, Kneba, Michael, Lange, Elisabeth, Langerbeins, Petra, Pflug, Natali, Kovacs, Gabor, Goede, Valentin, Fink, Anna-Maria, Elter, Thomas, Fischer, Kirsten, Wendtner, Clemens-Martin, Hallek, Michael and Eichhorst, Barbara (2015). 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). Haematologica, 100 (11). S. 1451 - 1460. PAVIA: FERRATA STORTI FOUNDATION. ISSN 0390-6078

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Abstract

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, P<0.0001). Univariate Cox regression analysis demonstrated that patients who did not receive antibody treatment had a 1.42-fold higher risk of death (hazard ratio, 1.42; 95% confidence interval: 1.185-1.694). Therapies administered at relapse were very heterogeneous. Only 55 of 368 patients (14.9%) who started second-line treatment > 24 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Cramer, PaulaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Isfort, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bahlo, JasminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stilgenbauer, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doehner, HartmutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bergmann, ManuelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stauch, MartinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kneba, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lange, ElisabethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langerbeins, PetraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pflug, NataliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kovacs, GaborUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goede, ValentinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fink, Anna-MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Elter, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, KirstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wendtner, Clemens-MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallek, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eichhorst, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-388754
DOI: 10.3324/haematol.2015.124693
Journal or Publication Title: Haematologica
Volume: 100
Number: 11
Page Range: S. 1451 - 1460
Date: 2015
Publisher: FERRATA STORTI FOUNDATION
Place of Publication: PAVIA
ISSN: 0390-6078
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
FLUDARABINE PLUS CYCLOPHOSPHAMIDE; PROGRESSION-FREE SURVIVAL; PHASE-II TRIAL; RITUXIMAB; CHLORAMBUCIL; BENDAMUSTINE; COMBINATION; EFFICACYMultiple languages
HematologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/38875

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