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 August 3, 2020.
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