Tocilizumab and Desensitization in Kidney Transplant Candidates: Personal Experience and Literature Review

Abstract

Desensitization (DES) allows kidney transplantation for highly HLA-sensitized subjects. Due to the central role of IL-6 in the immunological response, tocilizumab may improve DES efficacy. Thus, we conducted a PubMed systematic review using the MeSH terms tocilizumab, interleukin-6, kidney transplantation, and desensitization. Tocilizumab (TCZ) was first studied for DES as the second-line treatment after failure of a standard DES protocol (SP) (apheresis, rituximab +/- IVIg). Although TCZ (as a monotherapy) attenuated anti-HLA antibody rates, it did not permit transplantation. However, lymphocyte immuno-phenotyping has shown that TCZ hinders B-cell maturation and thus could improve the long-term efficacy of DES by limiting anti-HLA rebound and so avoid antibody-mediated rejection. This hypothesis is supported by a recent study where clazakizumab, a monoclonal antibody directed against IL-6, was continued after kidney transplantation in association with an SP. Nine out of ten patients were then eligible for transplantation, and there were no donor-specific antibodies at 6 months post-transplantation. In association with an SP, tocilizumab does not seem to significantly improve kidney-allograft access (short-term efficacy) vs. a SP only. However, it could improve the long-term prognosis of HLA-incompatible transplantation by hindering B-cell maturation and, thereby, avoiding donor-specific antibody rebounds post-transplantation.

Tocilizumab and Active Antibody-Mediated Rejection in Kidney Transplantation: A Literature Review

“…Finally, TCZ has also been used in desensitization protocols in highly sensitized kidney-transplant candidates ( 43 ). A decrease in the level of anti-HLA antibodies and the number of plasma cells producing these antibodies in the bone marrow and spleen with TCZ has been shown in mice.…”

Heart transplantation across preformed donor-specific antibody barriers using a perioperative desensitization protocol

“…This finding is in line with a published desensitization regimen in kidney transplantation, where tocilizumab alone did not lead to sufficient desensitization success but the addition of plasmapheresis and triple immunosuppression did. 33,34 In addition, the IVIG preparation used in this protocol also contains enriched IgM and IgA, which might contribute to the lower incidence of infectious complications in our cohort.…”

Addition of interleukin-6 receptor blockade to carfilzomib-based desensitization in a highly sensitized nonhuman primate model

“…21 Furthermore, IL-6 plays a central role in supporting PCs in the bone marrow. 22 As such, TCZ has been evaluated both as an adjunct to common desensitization protocols (Rituximab, IVIg, plasmapheresis [PP]) 23 and as monotherapy [24][25][26] with overall mixed results. In particular, TCZ monotherapy failed to desensitize patients in a clinically significant manner, suggesting that TCZ alone is not sufficient and compensatory mechanisms are likely at play.…”