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Safety, pharmacokinetics, and pharmacodynamic activity of obinutuzumab, a type 2 anti-CD20 monoclonal antibody for the desensitization of candidates for renal transplant.

  • Author(s): Redfield, Robert R
  • Jordan, Stanley C
  • Busque, Stephan
  • Vincenti, Flavio
  • Woodle, E Steve
  • Desai, Niraj
  • Reed, Elaine F
  • Tremblay, Simon
  • Zachary, Andrea A
  • Vo, Ashley A
  • Formica, Richard
  • Schindler, Thomas
  • Tran, Ha
  • Looney, Caroline
  • Jamois, Candice
  • Green, Cherie
  • Morimoto, Alyssa
  • Rajwanshi, Richa
  • Schroeder, Aaron
  • Cascino, Matthew D
  • Brunetta, Paul
  • Borie, Dominic
  • et al.

Published Web Location

https://doi.org/10.1111/ajt.15514
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).

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