Goede, Valentin, Fischer, Kirsten, Busch, Raymonde, Engelke, Anja, Eichhorst, Barbara, Wendtner, Clemens M., Chagorova, Tatiana, de la Serna, Javier, Dilhuydy, Marie-Sarah, Illmer, Thomas, Opat, Stephen, Owen, Carolyn J., Samoylova, Olga, Kreuzer, Karl-Anton, Stilgenbauer, Stephan, Doehner, Hartmut, Langerak, Anton W., Ritgen, Matthias, Kneba, Michael, Asikanius, Elina, Humphrey, Kathryn, Wenger, Michael and Hallek, Michael (2014). Obinutuzumab plus Chlorambucil in Patients with CLL and Coexisting Conditions. N. Engl. J. Med., 370 (12). S. 1101 - 1111. WALTHAM: MASSACHUSETTS MEDICAL SOC. ISSN 1533-4406

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Abstract

Background The monoclonal anti-CD20 antibody rituximab, combined with chemotherapeutic agents, has been shown to prolong overall survival in physically fit patients with previously untreated chronic lymphocytic leukemia (CLL) but not in those with coexisting conditions. We investigated the benefit of the type 2, glycoengineered antibody obinutuzumab (also known as GA101) as compared with that of rituximab, each combined with chlorambucil, in patients with previously untreated CLL and coexisting conditions. Methods We randomly assigned 781 patients with previously untreated CLL and a score higher than 6 on the Cumulative Illness Rating Scale (CIRS) (range, 0 to 56, with higher scores indicating worse health status) or an estimated creatinine clearance of 30 to 69 ml per minute to receive chlorambucil, obinutuzumab plus chlorambucil, or rituximab plus chlorambucil. The primary end point was investigator-assessed progression-free survival. Results The patients had a median age of 73 years, creatinine clearance of 62 ml per minute, and CIRS score of 8 at baseline. Treatment with obinutuzumab-chlorambucil or rituximab-chlorambucil, as compared with chlorambucil monotherapy, increased response rates and prolonged progression-free survival (median progression-free survival, 26.7 months with obinutuzumab-chlorambucil vs. 11.1 months with chlorambucil alone; hazard ratio for progression or death, 0.18; 95% confidence interval [CI], 0.13 to 0.24; P<0.001; and 16.3 months with rituximab-chlorambucil vs. 11.1 months with chlorambucil alone; hazard ratio, 0.44; 95% CI, 0.34 to 0.57; P<0.001). Treatment with obinutuzumab-chlorambucil, as compared with chlorambucil alone, prolonged overall survival (hazard ratio for death, 0.41; 95% CI, 0.23 to 0.74; P = 0.002). Treatment with obinutuzumab-chlorambucil, as compared with rituximab-chlorambucil, resulted in prolongation of progression-free survival (hazard ratio, 0.39; 95% CI, 0.31 to 0.49; P<0.001) and higher rates of complete response (20.7% vs. 7.0%) and molecular response. Infusion-related reactions and neutropenia were more common with obinutuzumab-chlorambucil than with rituximab-chlorambucil, but the risk of infection was not increased. Conclusions Combining an anti-CD20 antibody with chemotherapy improved outcomes in patients with CLL and coexisting conditions. In this patient population, obinutuzumab was superior to rituximab when each was combined with chlorambucil.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Goede, ValentinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, KirstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Busch, RaymondeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Engelke, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eichhorst, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wendtner, Clemens M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chagorova, TatianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de la Serna, JavierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dilhuydy, Marie-SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Illmer, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Opat, StephenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Owen, Carolyn J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Samoylova, OlgaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreuzer, Karl-AntonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stilgenbauer, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doehner, HartmutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langerak, Anton W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ritgen, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kneba, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Asikanius, ElinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Humphrey, KathrynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wenger, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallek, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-443227
DOI: 10.1056/NEJMoa1313984
Journal or Publication Title: N. Engl. J. Med.
Volume: 370
Number: 12
Page Range: S. 1101 - 1111
Date: 2014
Publisher: MASSACHUSETTS MEDICAL SOC
Place of Publication: WALTHAM
ISSN: 1533-4406
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CHRONIC LYMPHOCYTIC-LEUKEMIA; ILLNESS RATING-SCALE; GENOMIC ABERRATIONS; ANTI-CD20 ANTIBODY; 1ST-LINE THERAPY; PROGRESSION-FREE; INITIAL THERAPY; IN-VITRO; RITUXIMAB; FLUDARABINEMultiple languages
Medicine, General & InternalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/44322

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