Session Time: 2:15pm-3:45pm
Presentation Time: 3:27pm-3:39pm
Location: Terrace IV
Complement activation by preformed DSA is a major mechanism of acute antibody-mediated rejection (aAMR) in sensitized kidney transplant recipients (KTR). We previously reported interim study results showing eculizumab, a C5 inhibitor, appeared to be effective for prevention of aAMR in KTR sensitized to their deceased donors compared with historical controls. We report 1-yr data from this ongoing, open-label, single-arm trial.
Sensitized KTR defined as: current DSA >3000MFI as detected by SAB; or B-cell or T-cell flow cytometric crossmatch ≥300 and ≤500 mean channel shift; or historical positive complement-dependent cytotoxicity crossmatch to donor HLA. All recipients received eculizumab 1200mg postoperative day 0 prior to reperfusion, 900mg on postoperative day 1, 7, 14, and 28, and 1200mg at wks 5, 7, 9. Rabbit ATGa was used for induction and corticosteroids, tacrolimus, and mycophenolate for maintenance immunosuppression. Posttransplant plasmapheresis was not allowed. The primary composite endpoint was clinically significant, biopsy-proven aAMR grade II/ III (Banff 2007), (based on centrally read biopsy), death, graft loss, or loss to follow-up at 9wks posttransplant. Graft and patient survival were estimated by Kaplan-Meier.
80 candidates were transplanted (48 F, 32 M); median age 52y (range, 24-70). 9/80 KTR met the 9wk composite endpoint based on local biopsies (11.3% [95% CI 5.3%, 20.3%]). 5 of the 9 KTR had aAMR (6.3%) compared to 30% expected for historical controls. Graft survival at 6 and 12mo was 93.7% and 87.1%, respectively; patient survival at 6 and 12mo was 97.4%. Mean creatinine levels (mg/dL) at baseline, 1 and 12mo posttransplant were, 7.44 (±2.52), n=78; 1.86 (±1.07), n=74; and 1.80 (±1.11), n=45, respectively. No new safety signals were identified.
Eculizumab appeared to be effective in reducing the incidence of aAMR in sensitized deceased donor KTR. Patient and graft survival and kidney function at 1yr were similar to those expected for nonsensitized KTR. Eculizumab was well tolerated.
To cite this abstract in AMA style:Glotz D, Russ G, Rostaing L, Legendre C, Chadban S, Grinyo J, Mamode N, Cozzi E, Lebranchu Y, Sandrini S, Couzi L, Marks W. Eculizumab in Prevention of Acute Antibody-Mediated Rejection in Sensitized Deceased-Donor Kidney Transplant Recipients: 1-Year Outcomes [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/eculizumab-in-prevention-of-acute-antibody-mediated-rejection-in-sensitized-deceased-donor-kidney-transplant-recipients-1-year-outcomes/. Accessed July 19, 2018.
« Back to 2015 American Transplant Congress