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Background. Belatacept, a selective T-cell costimulation blocker, was associated with improved survival and renal function but also with a risk of posttransplant lymphoproliferative disorder (PTLD) in adult kidney transplant recipients in phase 3 trials. This registry examined long-term safety in Epstein–Barr virus (EBV)–seropositive kidney transplant recipients treated with belatacept. Methods. This US-based, prospective, voluntary, multicenter registry (Evaluating Nulojix Long-Term Safety in Transplant [ENLiST]) included adult EBV-seropositive kidney-only transplant recipients treated de novo (within 14 d of transplantation) with belatacept. Primary objectives were to estimate incidence rates of confirmed PTLD, central nervous system (CNS) PTLD, and progressive multifocal encephalopathy (PML). The minimum follow-up was 2 y. Results. Of 985 enrolled transplant recipients, 933 EBV-seropositive patients received belatacept, with 523 (56.1%) receiving concomitant tacrolimus at transplant (for up to 12 mo). By study end, 3 cases of non-CNS PTLD (incidence rate, 0.08/100 person-years), 1 case of CNS PTLD (0.03/100 person-years), and no cases of PML had been reported. Two patients with non-CNS PTLD received concomitant belatacept and tacrolimus and 1 received belatacept and lymphocyte-depleting therapy. Incidence rates were comparable between patients who received concomitant belatacept and tacrolimus and those who did not receive tacrolimus (0.09/100 person-years and 0.07/100 person-years, respectively; P = 0.96). Two of 4 patients with PTLD died, and 2 were alive at the end of the study. Cumulatively, 131 graft losses or deaths were reported by study end. Conclusions. Our results from the ENLiST registry, a large, prospective real-world study, showed that the incidence rates of PTLD and CNS PTLD in belatacept-treated EBV-seropositive transplant recipients were consistent with findings from previous phase 3 trials.

Background. Cytopenias, a common complication for immunosuppressed patients, are known to be associated with adverse transplant outcomes. However, there is little information on cytopenias in recipients treated with the costimulation blockade agent, belatacept. Methods. We compared cytopenia incidence and manifestations in patients undergoing kidney transplant at Emory University Hospital on tacrolimus and belatacept. To reduce selection bias, the tacrolimus group was narrowed to include only patients eligible for belatacept. Results. Of 1651 patients transplanted between 2009 and 2019, 187 (11%) experienced severe anemia, 309 (19%) experienced leukopenia, and 62 (4%) thrombocytopenia. On multivariable regressions, deceased-donor transplant, cytomegalovirus viremia, and thymoglobulin treatment were associated with risk of developing leukopenia, anemia, and thrombocytopenia. High-risk cytomegalovirus status was also associated with development of leukopenia and anemia. Additionally, azathioprine was associated with development of anemia, and both tacrolimus therapy and Caucasian race were associated with thrombocytopenia. Longitudinal quantifications of hematologic cell lines over the first-year posttransplant were extracted from generalized linear models fit using splines. Only hemoglobin range was significantly different between groups (greater in belatacept patients). Plots of mean cell count for each group suggest an earlier recovery from posttransplant anemia in belatacept patients. Conclusions. Belatacept patients are not at increased risk of cytopenia but may have improved recovery from posttransplant anemia.

Background. Costimulatory blockade with belatacept has demonstrated long-term benefits in renal transplantation, but de novo use in liver transplant recipients has resulted in increased rejection, graft loss, and death. However, belatacept conversion as a calcineurin inhibitor (CNI) avoidance strategy has not been studied and may be of benefit in liver transplantation where CNI-induced renal dysfunction and toxicity are barriers to improved outcomes. Methods. Using clinical data extracted from our institutional medical record, we report on 8 patients who underwent kidney after liver transplantation and were treated with belatacept-based immunosuppression and transient CNI therapy. Results. All patients tolerated belatacept therapy without any patient deaths or graft losses. No episodes of rejection, de novo donor-specific antibody formation, or major systemic infections were observed, and all patients demonstrated preserved liver and excellent renal allograft function. Patients received belatacept for a median duration of 13.2 mo, and at a median follow-up of 15.9 mo post–kidney transplant, 6 of 8 patients continued on belatacept with 3 completely off and 3 poised to transition off CNI. Conclusions. These findings are the first evidence that in liver transplant recipients requiring subsequent kidney transplantation, belatacept-based therapy can potentially facilitate CNI-free maintenance immunosuppression. This supports the possibility of belatacept conversion in stand-alone liver transplant recipients as a viable method of CNI avoidance.