Imlifidase Desensitization in Crossmatch-positive, Highly Sensitized Kidney Transplant Recipients: Results of an International Phase 2 Trial (Highdes). Issue 8 (20th July 2021)

• Record Type: Journal Article
• Authors: Jordan, Stanley C.; Legendre, Christophe; Desai, Niraj M.; Lorant, Tomas; Bengtsson, Mats; Lonze, Bonnie E.; Vo, Ashley A.; Runström, Anna; Laxmyr, Lena; Sjöholm, Kristoffer; Schiött, Åsa; Sonesson, Elisabeth; Wood, Kathryn; Winstedt, Lena; Kjellman, Christian; Montgomery, Robert A.
• Is Part Of: Transplantation. Volume 105:Issue 8(2021)
• Page Start: 1808
• Page End: 1817
• Publication Date: 2021-07-20
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000003496
• Languages: English
• ISSNs: 0041-1337

Abstract

Abstract : Supplemental Digital Content is available in the text. Abstract : Background: Highly HLA sensitized patients have limited access to life-saving kidney transplantation because of a paucity of immunologically suitable donors. Imlifidase is a cysteine protease that cleaves IgG leading to a rapid decrease in antibody level and inhibition of IgG-mediated injury. This study investigates the efficacy and safety of imlifidase in converting a positive crossmatch test to negative, allowing highly sensitized patients to be transplanted with a living or deceased donor kidney. Methods: This open-label, single-arm, phase 2 trial conducted at 5 transplant centers, evaluated the ability of imlifidase to create a negative crossmatch test within 24 h. Secondary endpoints included postimlifidase donor-specific antibody levels compared with predose levels, renal function, and pharmacokinetic/pharmacodynamic profiles. Safety endpoints included adverse events and immunogenicity profile. Results: Of the transplanted patients, 89.5% demonstrated conversion of baseline positive crossmatch to negative within 24 h after imlifidase treatment. Donor-specific antibodies most often rebounded 3–14 d postimlifidase dose, with substantial interpatient variability. Patient survival was 100% with graft survival of 88.9% at 6 mo. With this, 38.9% had early biopsy proven antibody–mediated rejection with onset 2–19 d posttransplantation. Serum IgG levels began to normalize after ~3–7 d posttransplantation. Antidrug antibody levels were consistent with previous studies. Seven adverse events in 6 patients were classified as possibly or probably related to treatment and were mild-moderate in severity. Conclusions: Imlifidase was well tolerated, converted positive crossmatches to negative, and enabled patients with a median calculated panel-reactive antibody of 99.83% to undergo kidney transplantation resulting in good kidney function and graft survival at 6 mo. Abstract :