Obinutuzumab: its use in the management of chronic lymphocytic leukemia

Introduction: Chronic lymphocytic leukemia (CLL) is the most common leukemia. Over the last 40 years, the evolution of chemotherapeutic options and the addition of the anti-CD20 antibody rituximab have improved response rates significantly. Obinutuzumab, a next generation CD20 antibody, continues that evolution.Areas covered: In this review, we discuss the pre-clinical and recent clinical experiences with obintuzumab and discuss its potential future role in the management of CLL as well as the interest in combining this next generation CD20 antibody with B-cell receptor pathway inhibitors. Obinutuzumab has a number of modifications that increase its efficacy relative to rituximab resulting in improved antibody-dependent cell-mediated cytotoxicity and direct cell death. These biological attributes have translated into improved clinical responses. The clinical superiority of obinutuzumab relative to rituximab is best demonstrated in the CLL11 trial. In this randomized Phase III trial, for patients requiring upfront CLL treatment, the combination of obinutuzumab and chlorambucil was found to result in improved response and progression-free survival relative to the combination of rituximab and chlorambucil.Expert opinion: Obinutuzumab has clear pre-clinical and clinical superiority to rituximab and will be a central agent in the evolving management of CLL.