Desensitization using bortezomib and high-dose immunoglobulin increases rate of deceased donor kidney transplantation

Jong Cheol Jeong, Enkthuya Jambaldorj, Hyuk Yong Kwon, Myung-Gyu Kim, Hye Jin Im, Hee Jung Jeon, Ji Won In, Miyeun Han, Tai Yeon Koo, Junho Chung, Eun Young Song, Curie Ahn, Jaeseok Yang

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Abstract

Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate. This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2 g/kg), a single dose of rituximab (375 mg/m2), and 4 doses of bortezomib (1.3 mg/m2). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients. There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83±16.0 (14952±5820) and 63±36.0 (10321±7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468-634.132; P1/40.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor-specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group. In conclusion, a desensitization protocol using bortezomib, highdose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients.

Original languageEnglish
Article numbere2635
JournalMedicine (United States)
Volume95
Issue number5
DOIs
Publication statusPublished - 2016 Jan 1

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ASJC Scopus subject areas

  • Medicine(all)

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Jeong, J. C., Jambaldorj, E., Kwon, H. Y., Kim, M-G., Im, H. J., Jeon, H. J., In, J. W., Han, M., Koo, T. Y., Chung, J., Song, E. Y., Ahn, C., & Yang, J. (2016). Desensitization using bortezomib and high-dose immunoglobulin increases rate of deceased donor kidney transplantation. Medicine (United States), 95(5), [e2635]. https://doi.org/10.1097/MD.0000000000002635