Kidney Week

Abstract: SA-PO479

Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection – A Double-Blind Randomized Placebo-Controlled Trial (BORTEJECT Study)

Session Information

• Transplantation: Balancing Rejection and Infection
  November 04, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Transplantation

• 1702 Transplantation: Clinical and Translational

Authors

• Eskandary, Farsad Alexander, Medical University Vienna, Vienna, Austria

Farsad Alexander Eskandary,

• Regele, Heinz, Medical University Vienna, Vienna, Austria

Heinz Regele,

• Bond, Gregor, Medical University Vienna, Vienna, Austria

Gregor Bond,

• Kozakowski, Nicolas, Medical University Vienna, Vienna, Austria

Nicolas Kozakowski,

• Wahrmann, Markus, Medical University Vienna, Vienna, Austria

Markus Wahrmann,

• Hidalgo, Luis G., University of Alberta, Edmonton, Alberta, Canada

Luis G. Hidalgo,

• Haslacher, Helmuth, Medical University Vienna, Vienna, Austria

Helmuth Haslacher,

• Kaltenecker, Christopher, Medical University Vienna, Vienna, Austria

Christopher Kaltenecker,

• Aretin, Bernadette, AKH-Wien, Vienna, Austria

Bernadette Aretin,

• Oberbauer, Rainer, Medical University Vienna, Vienna, Austria

Rainer Oberbauer,

• Reeve, Jeff, University of Alberta, Edmonton, Alberta, Canada

Jeff Reeve,

• Halloran, Philip F., University of Alberta, Edmonton, Alberta, Canada

Philip F. Halloran,

• Bohmig, Georg, Medical University Vienna, Vienna, Austria

Georg Bohmig,

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 randomized, double-blind, placebo-controlled, single-center phase 2 trial (NCT01873157), we investigated whether two cycles of the proteasome inhibitor bortezomib (each cycle: 1.3 mg/m2 on days 1, 4, 8 and 11) are able to halt the progression of late ABMR, using eGFR slope (Over 0, 3, 6, 12, 18 and 24 months) as primary endpoint (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.

Funding

• Government Support - Non-U.S.