Obinutuzumab (GA101) compared to rituximab significantly enhances cell death and antibody-dependent cytotoxicity and improves overall survival against CD20+ rituximab-sensitive/-resistant Burkitt lymphoma (BL) and precursor B-acute lymphoblastic leukaemia (pre-B-ALL): potential targeted therapy in patients with poor risk CD20+ BL and pre-B-ALL

Obinutuzumab is a novel glycoengineered Type-II CD20 monoclonal antibody. CD20 is expressed in approximately 100% of children and adolescents with Burkitt lymphoma (BL) and 40% with precursor B-cell acute lymphoblastic leukaemia (pre-B-ALL). We evaluated the anti-tumour activity of obinutuzumab versus rituximab against rituximab-resistant (Raji 4RH) and -sensitive (Raji) BL and pre-B-ALL (U698-M) cells in vitro and in human BL or Pre-B-ALL xenografted mice. We demonstrated that obinutuzumab compared to rituximab significantly enhanced cell death against Raji 35.6 +/- 3.1% vs. 25.1 +/- 2.0%, (P = 0.001), Raji4RH 19.7 +/- 2.2% vs. 7.9 +/- 1.5% (P = 0-001) and U-698-M 47.3 +/- 4.9% vs. 23.2 +/- 0.5% (P = 0.001), respectively. Obinutuzumab versus rituximab also induced a significant increase in antibody-dependent cellular cytotoxicity (ADCC) with K562-IL15-41 BBL expanded NK cells against Raji 73.8 +/- 8.1% vs. 56.81 +/- 4.6% (P = 0-001), Raji-4RH 40.0 +/- 1.6% vs. 0-5 +/- 1.1% (P = 0.001) and U-698-M 70.0 +/- 1.6% vs. 45.5 +/- 0.1% (P = 0.001), respectively. Overall survival in tumour xenografted mice receiving 30 mg/kg of obinutuzumab was significantly increased when compared to those receiving 30 mg/kg of rituximab in 13I,; Ran (P = 0.05), Raji4RH (P = 0.02) and U698-M (P = 0.03), respectively. These preclinical data suggest obinutuzumab is significantly superior to rituximab in inducing cell death, ADCC and against rituximab-sensitive/-resistant BL and pre-B-ALL xenografted mice. Taken together, these preclinical results provide evidence to suggest that future investigation of obinutuzumab is warranted in patients with relapsed/refractory CD20(+) BL and/or pre-B-ALL.