Abstract

The limited effectiveness of rituximab plus intravenous immunoglobulin (IVIG) in desensitization may be due to incomplete B-cell depletion. Obinutuzumab is a type 2 anti-CD20 antibody that induces increased B-cell depletion relative to rituximab and may therefore be more effective for desensitization. This open-label Phase 1b study assessed the safety, pharmacokinetics, and pharmacodynamics of obinutuzumab in highly sensitized patients with end-stage renal disease. Patients received 1 (day 1, n=5) or 2 (days 1 and 15; n=20) infusions of 1000-mg obinutuzumab followed by 2 doses of IVIG on days 22 and 43. Eleven patients received additional obinutuzumab doses at the time of transplant and/or at week 24. The median follow-up duration was 9.4 months. Obinutuzumab was well tolerated, and most adverse events were Grade 1-2 in severity. There were 11 serious adverse events (SAEs) in 9 patients (36%); 10 of these SAEs were infections and 4 occurred after kidney transplant. Obinutuzumab plus IVIG resulted in profound peripheral B-cell depletion and appeared to reduce B cells in retroperitoneal lymph nodes. Reductions in anti-HLA antibodies, number of unacceptable antigens, and the calculated panel reactive antibody score as centrally assessed by single-antigen bead assay were limited and not clinically meaningful for most patients (NCT02586051). This article is protected by copyright. All rights reserved.

View details for DOI 10.1111/ajt.15514

View details for PubMedID 31257724