Obinutuzumab (Gazyvaro®) in combination with bendamustine for the treatment of relapsed/refractory follicular lymphoma (FL)

Obinutuzumab (Gazyvaro®) is a recombinant monoclonal humanised and glycoengineered type II anti-CD20 antibody of the IgG1 subclass. It specifically targets the CD20 antigen expressed on the surface of non-malignant and malignant B lymphocytes. Thereby, obinutuzumab triggers B-cell lysis and antibody-dependent cellular cytotoxicity (ADCC). Currently, obinutuzumab is approved as combination therapy with chlorambucil for the treatment of patients with untreated chronic lymphocytic leukaemia (CLL) both in Europe and the US. Recently (February 2016), the US Food and Drug Administration (FDA) approved obinutuzumab for the treatment of patients with follicular lymphoma (FL), who did not respond or progressed during or up to 6 months after treatment with rituximab or a rituximab-containing regimen; also the European Medicines Agency (EMA) adopted a positive opinion for this indication. The FDA approval was based on the results of a phase III study, GADOLIN, which is available in abstract form only. 392 indolent non-Hodgkin lymphoma (iNHL) patients, of whom 81% had FL, were randomised to receive either obinutuzumab plus bendamustine, and after complete response (CR), partial response (PR), or stable disease (SD), patients received obinutuzumab maintenance therapy; or bendamustine monotherapy. The stratification of randomisation was based on the rituximab-refractory type and the number of prior therapies. The primary outcome of the study was progression-free survival (PFS). Patients of the obinutuzumab-bendamustine arm showed a significant increase in PFS (p < 0.0001); the median PFS was 13.8 months in the bendamustine arm and was not reached in the obinutuzumab-bendamustine group. In contrast, the secondary study endpoint, overall survival (OS), was not yet reached either by the obinutuzumab-bendamustine group or in the bendamustine arm. In terms of safety outcomes, the most common grade 3–4 adverse events (AEs) in the obinutuzumab-bendamustine as well as in the bendamustine group were neutropenia, pneumonia, thrombocytopenia and infusion-related reactions. Although the study shows a significant improvement in PFS, the lack of mature OS data, in addition to the fact that there was no difference in overall response (OR) highlights the need for long-term data. Furthermore, a long-term safety profile as well as further quality of life (QoL) data will be necessary to exclude any risks of late side effects. In addition, any original article presenting the study will need to identify potential advantages and disadvantages for specific subgroups.