Obinutuzumab: a novel anti-CD20 monoclonal antibody for previously untreated chronic lymphocytic leukemia.

OBJECTIVE: To review and summarize data on obinutuzumab, which was approved by the Food and Drug Administration (FDA) in November 2013 for use in combination with chlorambucil for previously untreated chronic lymphocytic leukemia (CLL).

DATA SOURCES: A PubMed literature search (August 2002 to March 2014) was conducted using the terms obinutuzumab, GA101, anti-CD20 antibody, and CLL. Data were also obtained through the FDA briefing documents and American Society of Hematology abstracts.

STUDY SELECTION AND DATA EXTRACTION: The literature search was limited to human studies published in English. Priority was placed on trials of obinutuzumab in previously untreated CLL.

DATA SYNTHESIS: Obinutuzumab is a novel glycoengineered type II anti-CD20 monoclonal antibody, with a higher affinity for CD20 epitope, leading to superior cytotoxicity compared with rituximab. The FDA approval was based on a phase III, randomized trial of chlorambucil monotherapy (n = 118), chlorambucil plus obinutuzumab (n = 333), or rituximab (n =330) in previously untreated elderly CLL patients. Obinutuzumab was administered intravenously as 1000 mg on days 1, 8, and 15 of cycle 1 and day 1 for subsequent cycles. Median progression-free survival was 26.7 months in the chlorambucil plus obinutuzumab arm. The incidence of grade 3 or higher adverse events in the obinutuzumab plus chlorambucil arm was as follows: neutropenia (33%), infusion-related reactions (20%), thrombocytopenia (10%), and infections (7%).

CONCLUSION: Obinutuzumab in combination with chlorambucil is a safe and effective new treatment option for previously untreated elderly CLL patients. It should become the new preferred therapy for these patients with significant comorbidities who are not candidates for fludarabine-based therapy.