The monoclonal anti-CD20 antibody Rituximab ( MabThera, Rituxan ), 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.
The benefit of the type 2, glycoengineered antibody Obinutuzumab ( also known as GA101; Gazyva ) as compared with that of Rituximab, each combined with Chlorambucil, in patients with previously untreated chronic lymphocytic leukemia and coexisting conditions, was investigated.
Researchers have randomly assigned 781 patients with previously untreated chronic lymphocytic leukemia 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.
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 versus 11.1 months with Chlorambucil alone; hazard ratio for progression or death, 0.18; P less than 0.001; and 16.3 months with Rituximab - Chlorambucil vs 11.1 months with Chlorambucil alone; HR=0.44; P less than 0.001 ).
Treatment with Obinutuzumab - Chlorambucil, as compared with Chlorambucil alone, prolonged overall survival ( hazard ratio for death, 0.41; P=0.002 ).
Treatment with Obinutuzumab - Chlorambucil, as compared with Rituximab - Chlorambucil, resulted in prolongation of progression-free survival ( HR=0.39; P less than 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.
In conclusion, combining an anti-CD20 antibody with chemotherapy improved outcomes in patients with chronic lymphocytic leukemia and coexisting conditions.
In this patient population, Obinutuzumab was superior to Rituximab when each was combined with Chlorambucil. ( Xagena )
Goede V et al, N Engl J Med 2014; 370:1101-1110