Obinutuzumab-Containing Multimodality Induction in Kidney Transplantation

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Background: Hard-to-match deceased donor kidney transplant (KT) candidates can rarely benefit from desensitization programs and often arrive at transplant with elevated donor-specific antibodies (DSA) levels. In this particular setting, current immunosuppressive strategies have been associated with exceedingly high antibodymediated rejection (AMR) rates and poor graft survivals. We report our experience with a novel induction protocol. Methods: We analysed data from 7 high-risk (PRA 95%, DSA >3000 MFI) deceased donor KT recipients who had been treated with the following scheme. One session of plasma exchange (PEX) was carried out before surgery and 3 sessions between post-op day 5 and 14. Patients received eculizumab 900 mg prior graft reperfusion. Post-op, they were given thymoglobulin 5 mg/kg total dose from day 0 to day 4, IV immunoglobulin 2 gr/kg total dose (after PEX), methylprednisolone, and obinutuzumab 1000 mg within 2 weeks of the last PEX. As maintenance, we used LCP-tacrolimus (C0, 10-15 ng/mL), mycophenolate mofetil (MMF, 2000 mg/day), and prednisone. Results: After a median follow-up of 13 (3-16) months, all patients were alive with a functioning allograft and a median serum creatinine of 1.6 (1.1-2.5) mg/dL. DGF was recorded in 5 recipients. Overall, we observed one episode of cell-mediated rejection and 2 episodes of AMR rejection in 2 patients. Notably, both cases of AMR were recorded before obinutuzumab could be administered (day 7 and day 13). By week 2 after obinutuzumab infusion, all subjects showed full CD19+ cell depletion with no signs of repopulation up to the last visit. Changes in anti-HLA antibodies were extremely variable, but no de novo DSA were identified. Obinutuzumab was not associated with infusion-related adverse events. One of the patients developed severe leukopenia requiring MMF withdrawal. Asymptomatic CMV, EBV, or BKV viraemia were detected in 57%, 14%, and 0% of the recipients, respectively. No features of AMR could be detected in protocol biopsies obtained 6 months after KT. Conclusions: Our experience shows that obinutuzumab induction is safe and effective in high-immunological risk KT recipients. Also, obinutuzumab-induced B-cell depletion appears to be uneffected by concomitant complement inhibition. Such encouraging findings should prompt further investigation.

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