A Randomized Trial of Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection.
Eskandary F, Regele H, et al.Journal of the American Society of Nephrology 2017; 14: 14.
Aims
To investigate the effect of the proteasome inhibitor bortezomib on late antibody-mediated rejection (ABMR) in kidney transplant recipients.
Interventions
Participants were randomised to receive two cycles at 3-month intervals of either bortezomib 1.3 mg/m2 administered intravenously twice weekly and oral valacyclovir for antiviral prophylaxis, (bortezomib group) versus 0.9% sodium chloride solution and hard gelatin capsules filled with maltodextrin (control group).
Participants
44 kidney transplant recipients aged >18 years, who were ≥180 days posttransplantation, had an estimated glomerular filtration rate (eGFR) >20 ml/min per 1.73 m2 with the detection of HLA class I and/or II donor-speciï¬c antibody (DSA) and showing ≥ one morphologic feature suggestive of ABMR
Outcomes
The primary outcome measured was the slope of eGFR computed from eGFR measurements at 0, 6, 12, 18, and 24 months. Secondary outcomes included the course of DSA, measured GFR, urinary protein excretion, patient and graft survival, occurrence of acute rejection necessitating treatment, and protocol biopsies at 24 months.
Follow-up
24 months
CET Conclusions
This paper reports the results of the Borteject Trial, in which kidney transplant recipients with donor-specific antibody and histological evidence of antibody-mediated rejection were randomised to Bortezomib or placebo. Despite the suggestion from a number of observational studies that Bortezomib reduces DSA and improves outcomes, this blinded RCT demonstrated no benefit in terms of renal function or DSA levels. Haematological and gastrointestinal toxicity were higher in the Bortezomib arm. The study is small (just 44 patients), powered to demonstrate a relatively large difference in GFR slope of 5 ml/min/year. However, given the absence of even a trend towards benefit or a reduction in DSA levels, it seems safe to say that in a late AMR population such as this, Bortezomib alone does not confer any clinical benefit.
Data analysis
Strict intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT01873157 and EUDRACT - 2012–002857–41