Impact of obinutuzumab alone and in combination for follicular lymphoma

Abstract

Although rituximab-based chemoimmunotherapy prolongs the survival of patients with follicular lymphoma (FL), this disease is considered incurable in most patients. Thus, new therapies are needed not only for those in the relapsed/refractory setting, but also for initial treatment. Obinutuzumab (G, GA101) is a third-generation, fully humanized type II glycoengineered, anti-CD20 monoclonal antibody that results in increased direct cell death and antibody-dependent, cell-mediated cytotoxicity/phagocytosis compared to rituximab. Obinutuzumab has significant antitumor activity when used alone or in combinations in untreated or relapsed refractory FL patients. Studies have demonstrated its ability to prolong progression-free survival and, in some cases, overall survival, and to eliminate minimal residual disease. Several ongoing trials are investigating combinations with chemotherapy, immunomodulators, targeted drugs, and immunotherapy agents. G is generally well tolerated, with associated adverse effects including infusion-related reactions, neutropenia, thrombocytopenia, and reactivation of hepatitis B virus. Future studies with this antibody should focus on identifying predictive markers and developing chemotherapy-free combinations that will improve the outcome of patients with FL.