title: Update on obinutuzumab in the treatment of B-cell malignancies.
abstract: BACKGROUND
  The anti-CD20 mAb rituximab has revolutionized the treatment of B-cell malignancies, improving outcome for patients. Despite these improvements, the majority of patients still relapse and become refractory to rituximab. Further efforts to improve anti-CD20 mAb efficacy have recently focused on obinutuzumab /GA101, a novel anti-CD20 mAb glycoengineered to display enhanced Fc-mediated effector mechanisms and induce direct cell death.
  
  
  METHODS
  We provide an overview of the current insights into the mechanisms of action of obinutuzumab focusing on how structural modifications and differences to rituximab led to designation of obinutuzumab as a type II antibody. We summarize data from preclinical studies and recent clinical trials including the Phase III trial in chronic lymphocytic leukemia (CLL), which led to FDA approval in November 2013.
  
  
  CONCLUSIONS
  Clinical data are now emerging confirming the promise of the initial preclinical data that demonstrated superior efficacy of obinutuzumab over rituximab at similar dosing. The emerging randomized Phase III data from older comorbid patients with previously untreated CLL demonstrated significant improvements in molecular remission rates and median progression-free survival of obinutuzumab plus chlorambucil versus rituximab plus chlorambucil. This emerging data provide reasons to be optimistic that outcomes for patients with B-cell malignancies can be further improved with obinutuzumab.
authors.affiliation: University of Manchester, Institute of Cancer Sciences, The Christie Hospital, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre , Manchester M20 4BX , UK +44 0 161 446 8110 ; +44 0 161 446 8001 ; tmi@manchester.ac.uk.
authors.forename: Tim
authors.initials: T
authors.lastname: Illidge
authors.forename: Eleanor J
authors.initials: EJ
authors.lastname: Cheadle
authors.forename: Claire
authors.initials: C
authors.lastname: Donaghy
authors.forename: Jamie
authors.initials: J
authors.lastname: Honeychurch
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C543332:obinutuzumab
keywords: CD20; antibody; chronic lymphocytic leukemia; glycoengineering; non-Hodgkin lymphoma; obinutuzumab