Obinutuzumab (GA101) for the Treatment of Chronic Lymphocytic Leukemia and Other B-Cell Non-Hodgkin's Lymphomas: A Glycoengineered Type II CD20 Antibody

Abstract

Obinutuzumab (GA101) is a humanized, monoclonal type II CD20 antibody modified by glycoengineering. The glycoengineered Fc portion enhances the binding affinity to the FcγRIII receptor on immune effector cells, resulting in increased antibody-dependent cellular cytotoxicity and phagocytosis. In addition, the type II antibody binding characteristics of obinutuzumab to CD20 lead to an efficient induction of direct non-apoptotic cell death. Preclinical data demonstrated more efficient B-cell depletion in whole blood and superior antitumor activity in xenograft models of obinutuzumab as compared to the type I CD20 antibody rituximab. In previously untreated patients with chronic lymphocytic leukemia (CLL) and comorbidities, obinutuzumab plus chlorambucil increased response rates and prolonged progression-free survival compared with rituximab plus chlorambucil. Obinutuzumab had an acceptable and manageable safety profile, with infusion-related reactions during the first infusion as the most common adverse event. Further phase I/II clinical trials have also shown promising activity in other CD20-positive B-cell non-Hodgkin's lymphomas (NHL). Therefore, several clinical studies are planned or ongoing to investigate obinutuzumab with different combination partners in both untreated and relapsed/refractory patients with different B-cell NHL entities, which in addition to CLL include diffuse large B-cell lymphoma and follicular lymphoma.