Currently, all proposed treatments for desensitivation are often ineffective or transient (plasmapheresis, intravenous immunoglobulin or rituximab) to control the production of antiHLA antibodies by B or plasma memories cells. Bortezomib (BTZ), a proteasome inhibitor active against multiple myeloma in association with steroids has been proposed to desensitize patients with alloimmunization. Used alone, the results are contradictory. The objective of this study is to investigate the effect of corticosteroids and BTZ on the reduction of anti-HLA antibodies before renal transplantation.
Materials and methods
It is a prospective monocentric study taking place from March 2009 to February 2011. Patients included had a stable immunization against HLA, and were awaiting kidney transplantation.
Treatment consisted of Velcade ® (BTZ) 1.3 mg/m2 on days 1, 3, 7 and 9 associated with 40mg of dexamethasone intravenously. Anti HLA class 1 and 2 were determined by Luminex single antigen at D0, M1, M3 and M6.
Twenty-three patients were included and had an average number of anti-HLA antibodies on day 0 of 49, 31 corresponding to Class 1 and 18 to Class 2. At D0, the MFI (mean fluorescence) was 10,627 for class 1 immunodominant antibody and 7577 class 2. Eleven (47.5%) patients had a decrease of more than 25% of the class 1 immunodominant antibody at M3 1 and 15 (65%) at M6. Seven (32%) patients had a decrease of more than 25% of the Class 2 immunodominant antibody at M3 and 11 (50%) at M6. A M3, 51% of anti-HLA antibodies have declined by more than 25% (MFI) and 31% over 50%. This effect was maintained at M6, 58% of anti-HLA antibodies have declined by more than 25% and 41.5% over 50%.
Including any previously received treatment, no factor were predictive of antibody decline after BTZ. No serious adverse events have been observed. Nine of 23 patients were transplanted successfully thereafter.
Associated with corticosteroids, BTZ is an effective alternative therapy for reducing the rate of class 1 and 2 of anti HLA, regardless of the previous use of other treatments such as Rituximab prior or IVIg.
To cite this abstract in AMA style:Aubert O, Suberbielle C, Gauthe R, Nnang E, Francois H, Durrbach A. Effect of Proteasom Inhibition with Bortezomib Associated with Steroids on the Decrease of HLA Antibodies before Transplantation [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/effect-of-proteasom-inhibition-with-bortezomib-associated-with-steroids-on-the-decrease-of-hla-antibodies-before-transplantation/. Accessed October 23, 2020.
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