• DOI:10.1056/NEJMoa1313984
• Corpus ID: 12594312

Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions.

@article{Goede2014ObinutuzumabPC,
  title={Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions.},
  author={Valentin Goede and Kirsten Fischer and Raymonde Busch and Anja Engelke and Barbara F. Eichhorst and Clemens M. Wendtner and Tatiana Chagorova and Javier de la Serna and M. S. Dilhuydy and Thomas Illmer and Stephen S Opat and Carolyn J. Owen and Olga S. Samoylova and Karl Anton Kreuzer and Stephan Stilgenbauer and Hartmut D{\"o}hner and Anton W. Langerak and Matthias Ritgen and Michael Dr. Kneba and Elina Asikanius and Kathryn Humphrey and Michael K. Wenger and Michael Hallek},
  journal={The New England journal of medicine},
  year={2014},
  volume={370 12},
  pages={
          1101-10
        }
}

• V. Goede, K. Fischer, +20 authors M. Hallek
• Published 19 March 2014
• Medicine
• The New England journal of medicine

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. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT01010061.).