Results of the German CLL11 randomized, controlled clinical trial promise to change the standard of care for first-line treatment of older, sicker patients with chronic lymphocytic leukemia (CLL). The study showed that obinutuzumab (an anti-CD20 monocolonal antibody) plus chlorambucil (OC) was superior to rituximab plus chlorambucil (RC) with an acceptable safety profile, according to final results of the CLL11 trial, which were presented at the American Society of Hematology (ASH) annual meeting. OC prolonged overall survival and progression-free survival, and also improved complete response rate, and minimal residual disease (MRD)-negative status versus RC.
“These results suggest that obinutuzumab can replace rituximab in combination with chlorambucil as first-line therapy in the specific population studied, ie, older patients with comorbidities,” said Valentin Goede, MD, University Hospital Cologne, Germany.
“These findings are significant and potentially practice changing for this large patient population of older CLL patients with comorbidities.”
Goede noted that OC has less toxicity than RC, which is especially important in this compromised patient population that resembles compromised patients with CLL seen in the real world.
CLL11 randomized 781 patients in a 2:1:2 ratio to 3 arms: OC for 6 cycles; chlorambucil for 6 cycles (control); and RC for 6 cycles. At ASH, Goede presented the first results of the direct comparison between OC and RC (but not vs chlorambucil alone).
More grade >3 infusion reactions were initially seen with OC, mainly occurring with the first infusion: 20% with OC compared with 4% with RC. Once this reaction became evident, prophylaxis is now used and fewer infusion reactions are seen. OC did not increase the risk of infection versus RC, he said.
OC was significantly better than RC in achieving response rates and eradication of disease in blood and bone marrow; overall response rates were 78% versus 65%, respectively. The rate of MRD negativity in bone marrow was 19.5% for OC compared with 2.6% for RC (P <.0001); MRD-negative status in blood was achieved in 37.3% versus 3.3%, respectively (P <.0001).
OC led to a 61% improvement in the likelihood of achieving progression-free survival (the primary end point): median progression-free survival was 26.7 months versus 15.2 months for RC (P<.0001).
Overall survival data are not yet mature but, at present, survival is trending toward OC, Goede said.
Reference
Goede V, Fischer K, Busch R, et al. Head-to-head comparison of obinutuzumab (GA101) plus chlorambucil (Clb) versus rituximab plus Clb in patients with chronic lymphocytic leukemia (CLL) and co-existing medical conditions (comorbidities): final stage 2 results of the CLL11 trial. Presented at: 2013 American Society of Hematology Annual Meeting; December 8, 2013; New Orleans, LA. Abstract 6.
