Obinutuzumab: A Novel Anti-CD20 Monoclonal Antibody for Chronic Lymphocytic Leukemia.

Authors' disclosures of potential conflicts of interest are found at the end of this article. T he management of chronic lymphocytic leukemia (CLL), a malignant disorder of the lymphoid lineage (primarily B cells), has changed considerably in recent years. The development of agents targeting CD20, a trans-membrane calcium channel protein expressed on B cells, was a significant milestone in the management of various lymphomas and leukemias Rituximab (Rituxan), the first anti-CD20 monoclonal antibody, was originally approved by the US Food and Drug Administration (FDA) in 1997 for the treatment of non-Hodg-kin lymphoma and subsequently for CLL. The German CLL8 study compared fludarabine and cyclophos-phamide with or without rituximab in 761 previously untreated patients with CLL and demonstrated significant improvements in complete response, median progression-free survival (PFS), and overall survival (OS) in those who received ritux-imab (Hallek et al., 2010). This study thus established chemoimmunother-apy as the standard of care in young, symptomatic patients with CLL. A second anti-CD20 monoclonal antibody, ofatumumab (Arzerra), was granted accelerated approval by the FDA in 2009 for patients with fluda-rabine-refractory/alemtuzumab-refractory CLL and subsequently in 2014 for previously untreated patients with CLL unable to tolerate fludara-bine-based chemotherapy (Wierda et al., 2010, GlaxoSmithKline, 2014). This updated indication was based on a randomized trial comparing ofatumumab plus chlorambucil vs. chlorambucil alone in 447 treatment-naive patients with CLL (Hillmen et al., 2013). Overall response and PFS were significantly longer in the ofatu-mumab-chlorambucil group. In November 2013, the third anti-CD20 monoclonal antibody, obinu