Results of OBZ in FL confirm the interest for FcγRIIIA-mediated mechanisms, with some limitations, some of them being possibly due to lack of OBZ-induced complement activation. The results obtained for OBZ in CLL provide new arguments for FcγRIIIA-mediated mechanisms when the target antigen is expressed at a low density.
Moreover, the use of a different dosing regimen for RTX and OBZ further complicates any interpretation of clinical results. However, RTX differs from OBZ in 2 critical independent properties: being a type I anti-CD20 mAb and not being Fc-optimized. Rituximab (RTX) is frequently considered as its "ancestor" and OBZ clinical development was justified by the importance of FcγRIIIA-mediated mechanisms in RTX clinical activity. Obinutuzumab (OBZ) is a recombinant type II anti-CD20 and immunoglobulin G1 Fc-optimized monoclonal antibody (mAb), recently approved in chronic lymphocytic leukemia (CLL B-cell CLL) and follicular lymphoma (FL).
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