Obinutuzumab for the treatment of patients with previously untreated chronic lymphocytic leukemia: overview and perspective

Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder in the Western world and predominantly affects older people. Until recently, most studies in CLL focused on younger patients in whom intensive therapy with the addition of rituximab to fludarabine and cyclophosphamide was shown to improve survival. Obinutuzumab is a novel type II anti-CD20 monoclonal antibody (mAb) that recently demonstrated an overall survival advantage when combined with chemotherapy in previously untreated older patients with CLL and comorbidities. Obinutuzumab was superior to rituximab in this same study in terms of response rates and progression-free survival. Several preclinical and early phase clinical studies also support the efficacy of obinutuzumab. The most frequent adverse event noted with obinutuzumab is infusion-related reactions, which occur more frequently than with rituximab and are typically restricted to the first cycle of therapy. Based on these results, obinutuzumab should be considered the gold standard mAb for combination with chemotherapy in previously untreated patients with CLL and comorbidities. The marked efficacy of obinutuzumab with a weak chemotherapy backbone implies significant potency of this mAb, making it the ideal partner for combination studies with other agents in CLL.