Obinutuzumab (GA101), a New Generation Rituximab

By Peter Martin, MD

Rituximab is a chimeric (human-mouse) monoclonal antibody directed against the protein CD20 on the surface of B-lymphocytes and most B-cell lymphomas. Several clinical trials have demonstrated that rituximab can increase response rates, prolong remissions, and improve survival among patients with various B-cell lymphomas and is an FDA-approved drug. Interestingly, rituximab was developed during an era when our understanding of how monoclonal antibodies might work was relatively naïve. Obinutuzumab (GA101) is a newer generation anti-CD20 antibody that has undergone significant engineering to capitalize on new knowledge. In preclinical testing, GA101 appeared to work better than rituximab. Three clinical trials evaluating GA101 in patients with follicular lymphoma were presented at the American Society of Hematology (ASH) meeting this year.

Dr. Gilles Salles presented the results of a phase I/II study performed in France, in which patients with indolent non-Hodgkin lymphoma (mostly follicular lymphoma). In phase I of the study, patients were treated with escalating doses of GA101, while in phase 2, patients were randomized between two dose levels (high-dose and low-dose). Most patients had received prior rituximab. Overall, GA101 appeared to be well tolerated, with mild infusion reactions being the most common side effect. The results were encouraging, particularly in the high-dose group, but will need to be confirmed with a larger study and longer follow-up.

Dr. John Radford presented the results of the international GAUDI study, which evaluated the safety and efficacy of combining GA101 with CHOP or FC chemotherapy in patients with previously treated follicular lymphoma. Patients were randomized to two dose levels of GA101 (standard doses of chemotherapy were used) and responders were offered up to two years of maintenance therapy with GA101. Mild infusion reactions, most commonly during the first infusion, were the most common side effect and did not appear to be dose dependent. The authors reported that response rates to G-CHOP compared favorably to R-CHOP. It should be noted that only a randomized phase 3 trial can answer the question of whether G-CHOP or R-CHOP is better—such a trial is currently ongoing at several centers around the world.

Dr. Laurie Sehn presented the results of the international randomized phase 2 GAUSS study, which compared the response rates of GA101 and rituximab in patients with indolent lymphoma (mostly follicular lymphoma). All patients had received prior treatment including rituximab. GA101 was associated with a higher incidence of infusion reactions than rituximab (72% vs. 49%, mostly mild and most common during the first infusion). GA101 also resulted in a modest increase in response rate (15.2%) compared to rituximab, providing sufficient impetus to continue evaluation of the antibody in larger phase 3 studies.


Author: lymphomaprogram

Located on the Upper East Side of New York City, the Lymphoma Program at Weill Cornell Medical College/NewYork Presbyterian Hospital is internationally recognized for our efforts to enable patients with non-Hodgkin lymphoma, Hodgkin disease and related disorders to have the best possible clinical outcome, including cure when possible.

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