Obinutuzumab in kidney transplantation: Past, present, and future

Antibody-mediated rejection (ABMR) and recurrent primary renal disease (PRD) represent major causes of kidney transplant (KT) loss. The standard of care for desensitization, ABMR, and relapsing autoimmune glomerulopathies or nephrotic syndrome includes apheresis for antibody removal and polyclonal immunoglobulin for antibody blockage. Although frequently used to achieve B-cell depletion, the administration of the type 1 anti-CD20 monoclonal antibodies (mAb) rituximab (RTX) or ofatumumab (OFA) has failed to demonstrate a significant survival benefit. Obinutuzumab (OBI) is a humanized glycoengineered type 2 anti-CD20 mAb. Compared to RTX or OFA, OBI-induced B-cell depletion is not related to complement-dependent cytotoxicity, mostly operating through antibody-dependent cell-mediated cytotoxicity, antibody-dependent phagocytosis, and direct cell death. These characteristics could play a pivotal role in the development of new anti-rejection strategies, enabling the simultaneous administration of complement inhibitors and B-cell-depleting agents. OBI has also demonstrated more powerful peripheral and central B-cell depletion capacities than RTX, with enhanced effects on memory B cells and plasmablasts. In patients with autoimmune glomerulopathies or multidrug-dependent nephrotic syndrome, OBI has shown encouraging results, representing a potential evolution of the treatment of post-transplant relapsing PRD. The present review summarizes the current knowledge on OBI use in KT setting.