Switching renal transplant recipients to belatacept therapy: results of a real-life gradual conversion protocol

Costimulation Blockade in Kidney Transplant Recipients

“…In this study, 35 KTRs with a contraindication for CNIs were converted to belatacept after a median of 3.3 years (interquartile range 1.3-7.2) after transplantation [90]. Only one patient had a biopsy-proven AR that responded well to glucocorticoid pulse therapy [90]. The urinary CXCL9 concentration was elevated during AR.…”

“…Serial measurements (at 1-, 3-, 6-, and 12-month time points) of urine chemokine (C-X-C motif) ligand 9 (CXCL9) were used to screen for AR non-invasively. In this study, 35 KTRs with a contraindication for CNIs were converted to belatacept after a median of 3.3 years (interquartile range 1.3-7.2) after transplantation [90]. Only one patient had a biopsy-proven AR that responded well to glucocorticoid pulse therapy [90].…”

“…In addition, since belatacept must be administered intravenously, it has the potential advantage of providing better compliance, for instance in adolescent KTRs [85]. Several approaches for conversion to belatacept have been evaluated, such as early or late conversion [77,[86][87][88][89], belatacept combined with a short period of tacrolimus therapy [48], and non-invasive screening for AR after conversion to belatacept to detect AR at an early stage [90]. In a phase II, prospective, randomized trial, KTRs with a stable kidney function were randomized, 6-36 months after transplantation, to maintenance therapy with either belatacept (n = 84) or CNIs (n = 89) [88].…”

“…The combination of belatacept with 9 months of tacrolimus reduced the risk of aTCMR in a retrospective, single-center study (the 1-year aTCMR rate of belatacept therapy, tacrolimus therapy, and belatacept plus 9 months of tacrolimus was 50%, 20.5%, and 16%, respectively), without an increased incidence of infections [48]. Malvezzi et al also examined a strategy to safely convert KTRs to belatacept [90]. After the start of belatacept, the dose of tacrolimus was gradually reduced and withdrawn after 2 months.…”

“…3). The risk of belatacept-resistant AR is reduced when it is used in combination with a short period, or low-dose, of tacrolimus [48,90]. Belatacept therapy influences the immunosuppressive function of Tregs [51][52][53][54][55]; therefore, the combination of belatacept with therapies that preserve Treg functionality, such as mTOR inhibitors, T-cell-depletion therapy, anti-CD40 antibodies, and adoptive therapy with Tregs could possibly lead to a more precise control of alloimmunity (Fig.…”