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 using single-antigen bead assay were limited and not clinically meaningful for most patients (NCT02586051).
Original language | English (US) |
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Pages (from-to) | 3035-3045 |
Number of pages | 11 |
Journal | American Journal of Transplantation |
Volume | 19 |
Issue number | 11 |
DOIs | |
State | Published - Nov 1 2019 |
Keywords
- B cell biology
- alloantibody
- clinical research/practice
- clinical trial
- immunosuppressant — fusion proteins and monoclonal antibodies: B cell specific
- immunosuppression/immune modulation
- kidney transplantation/nephrology
- pharmacology
ASJC Scopus subject areas
- Immunology and Allergy
- Transplantation
- Pharmacology (medical)