Obinutuzumab: A Review of Its Use in Patients with Chronic Lymphocytic Leukaemia

Abstract

Obinutuzumab (Gazyva(®); Gazyvaro(®)) is an intravenously administered, glycoengineered, humanized, type II, anti-CD20 monoclonal antibody of the IgG1 subclass. It is available in the EU and the USA as combination therapy with oral chlorambucil in adults with previously untreated chronic lymphocytic leukaemia (CLL). In a multinational phase III study in this patient population, obinutuzumab plus chlorambucil significantly prolonged progression-free survival compared with oral chlorambucil alone and intravenous rituximab plus oral chlorambucil. Significant advantages with obinutuzumab plus chlorambucil over chlorambucil alone and rituximab plus chlorambucil were also observed in event-free survival, the time to a new anti-leukaemia treatment and overall response. The overall survival benefit with obinutuzumab plus chlorambucil is as yet unclear, although the most recent analysis suggests a benefit over chlorambucil alone. In the phase III study, obinutuzumab plus chlorambucil had a manageable tolerability profile in accordance with what would be expected for an anti-CD20 antibody. Neutropenia and infusion-related reactions were the most frequently reported grade 3 or higher treatment-emergent adverse events. In the majority of patients, infusion-related reactions were mild to moderate in severity and occurred predominantly during the first infusion and were managed by slowing or temporarily halting the infusion. Thus, current evidence suggests that obinutuzumab plus chlorambucil is a welcome addition to the treatment options currently available for adults with previously untreated CLL and is recommended by the National Comprehensive Cancer Network guidelines as the preferred first option for some, including those with comorbidities.

Obinutuzumab in the treatment of autoimmune haemolytic anaemia and immune thrombocytopenia in patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma

“…They contain proteins and RNAssuch as microRNAs (miRNAs)which are taken up by nearby and distant cells, thereby enabling genetic material and signalling proteins to be transferred among cells. 1,2 The role of exosomes in patients with haematological malignancies has not been studied as extensively as in solid cancers. The limited information available indicates that exosomes play roles in cell development, functional integrity, and progression to haematological malignancy.…”

“…Obinutuzumab is a type II, glycoengineered, humanized anti-CD20 monoclonal antibody, with enhanced direct cell death and antibody-dependent cell-mediated cytotoxicity. 1 Obinutuzumab is FDA-approved for chronic lymphocytic leukaemia (CLL) in combination with chlorambucil, ibrutinib or venetoclax as a first-line treatment. [2][3][4] Similar to rituximab, obinutuzumab induces B-cell depletion and reduced antibody production, granting it the potential to effectively treat antibody-mediated autoimmune phenomena.…”

The preclinical discovery of rituximab for the treatment of non-Hodgkin’s lymphoma

“…GA101 was shown to exert cytotoxicity in RTX-resistant cell lines [156,157]. Most recently, obinutizumab has been approved for the first-line treatment of less-fit CLL patients [158]. …”

Unexpected cross-reactivity of anti-cathepsin B antibodies leads to uncertainties regarding the mechanism of action of anti-CD20 monoclonal antibody GA101

“…Obinutuzumab (GA101) is a Type II humanized mouse IgG1κ anti-CD20 antibody with a glycoengineered Fc fragment [15] to enhance Fc receptor binding affinity (in particular for FcγRIIIa). GA101 is currently under phase III clinical trials for the treatment of patients with NHL [16,17] and has been approved for patients with previously untreated CLL [18][19][20][21]. In vivo studies have indicated superior anti-lymphoma activity for this third-generation anti-CD20 antibody over rituximab [15,22,23].…”