Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection – A Double-Blind Randomized Placebo-Controlled Trial (BORTEJECT Study)
1Nephrology and Dialysis, Medical University Vienna, Viena, Austria
2Institute of Clinical Pathology, Medical University Vienna, Vienna, Austria
3Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada
4Department of Laboratory Medicine, Medical University Vienna, Vienna, Austria
5Pharmacy Department, General Hospital Vienna, AKH, Vienna, Austria
6Alberta Transplant Applied Genomics Centre, University of Alberta, Edmonton, AB, Canada.
Meeting: 2018 American Transplant Congress
Abstract number: 204
Keywords: HLA antibodies, Kidney transplantation, Rejection, Renal function
Session Information
Session Name: Concurrent Session: Kidney Chronic Antibody Mediated Rejection
Session Type: Concurrent Session
Date: Monday, June 4, 2018
Session Time: 2:30pm-4:00pm
Presentation Time: 2:30pm-2:42pm
Location: Room 4B
Background. Antibody-mediated rejection (ABMR) is a leading cause of long-term kidney transplant loss. Optimal treatment of late ABMR is unclear, and our current knowledge is mostly based on uncontrolled studies. Methods. In this double-blind, placebo-controlled RCT(NCT01873157), we investigated whether two cycles of bortezomib (1.3mg/m[sup2]) are able to halt eGFR decline in late ABMR over 24 months as primary endpoint (eGFR slopes; 44 patients; 1:1 randomization). Secondary outcomes were mGFR at 24 months, donor-specific antibody (DSA) course and morphological/molecular results of 24-month follow-up biopsies. Results. Upon systematic cross-sectional HLA antibody screening of 741 recipients [inclusion criteria: age >18a, eGFR >20 ml/min/1.73 m2 at ≥180 days post-transplantation] we identified 111 recipients with DSA. Forty-four DSA+ recipients with morphological evidence of ABMR were included in the trial. Twenty-one patients were allocated to receive bortezomib, and 23 placebo. Despite a trend in reduction of DSA levels, bortezomib neither affected eGFR decline (bortezomib vs. placebo: -4.6 ± 2.7 vs. -4.8 ± 2.5 ml/min/1.73 m2/year), nor median mGFR at 24 months [33mL (IQR: 28-40) vs. 43mL (26-51), p=0.2]. There were also no differences regarding two-year overall graft survival (81% vs. 96%, p=0.1) and morphological (ABMR category, g+ptc score, IFTA score, C4d) and molecular results (Molecular-ABMR score, MMDx) of 24-month follow-up biopsies. Bortezomib treatment was associated with a higher rate of GI adverse events (diarrhea: 67% vs. 22%, p=0.005) and thrombo- and leukocytopenia. Conclusion. The BORTEJECT trial demonstrates that proteasome inhibition does not ameliorate the two-year course of late ABMR. Our results underscore the need for randomized trials to dissect the efficiency and safety of new treatment strategies in this context.
CITATION INFORMATION: Eskandary F., Regele H., Bond G., Kozakowski N., Wahrmann M., Hidalgo L., Haslacher H., Kaltenecker C., Aretin M-.B., Oberbauer R., Reeve J., Halloran P., Böhmig G. Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection – A Double-Blind Randomized Placebo-Controlled Trial (BORTEJECT Study) Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Eskandary F, Regele H, Bond G, Kozakowski N, Wahrmann M, Hidalgo L, Haslacher H, Kaltenecker C, Aretin M-B, Oberbauer R, Reeve J, Halloran P, Böhmig G. Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection – A Double-Blind Randomized Placebo-Controlled Trial (BORTEJECT Study) [abstract]. https://atcmeetingabstracts.com/abstract/bortezomib-in-late-antibody-mediated-kidney-transplant-rejection-a-double-blind-randomized-placebo-controlled-trial-borteject-study/. Accessed May 11, 2025.« Back to 2018 American Transplant Congress