A commonly used combination treatment for CLL consists of chemotherapy and rituximab, a synthetic molecule engineered to target a protein on the surface of CLL cells (CD20).
While effective, rituximab has less potency in CLL than in other cancers, and chemotherapy used in combination with rituximab may not be well tolerated among elderly patients.
In an effort to improve treatment options for CLL patients, investigators conducted a head-to-head comparison of rituximab and obinutuzumab (GA101), a novel monoclonal antibody engineered to attack CD20, but hypothesized to have more potent anti-leukaemic effects.
To test their hypothesis, investigators enrolled 781 patients (average age 73) and split them into three treatment arms: one arm received GA101 in combination with the standard chemotherapy chlorambucil (Clb; GClb, n=333), a second arm received rituximab and Clb (RClb, n=330), and a third arm received Clb alone (n=118). In combination with Clb, GA101 demonstrated more anti-leukaemic activity than rituximab, leading to a statistically significant and clinically meaningful prolongation of the median progression-free survival (26.7 months in the GClb arm and 15.2 months in the RClb arm) as well as a higher overall response rate (78% GClb vs. 65% RClb) with acceptable toxicity and no added risk of infection.
“Our results suggest that GA101 may be a stronger CD20 antibody than rituximab. This could lead to a potential decrease in the total amount of chemotherapy required for an effective combination regimen, translating to less toxicity for the patient,” said study author Valentin Goede, MD, of University Hospital Cologne in Germany. “While we will continue to evaluate these results through a longer follow-up period, these findings suggest that GA101 has the potential to eventually replace rituximab for the care of CLL patients.”