Tailored use of belatacept in adolescent kidney transplantation

Abstract

Adolescent transplant recipients are at risk for nonadherence, development of de novo donor‐specific antibody (dnDSA), and allograft loss. Belatacept, a selective T cell costimulatory blocker, is associated with reduced dnDSA, improved renal function, and prolonged allograft survival when compared to calcineurin inhibitor‐based regimens in adults; however, its use in children is scant. Three adolescents were initiated on belatacept between August 2017 and September 2018 at the time of kidney transplantation. Selection criteria included age ≥ 14 and EBV IgG + serostatus. Intraoperative alemtuzumab and methylprednisolone were given as induction therapy. Tailored maintenance therapy included steroid‐free belatacept and sirolimus for two patients. One patient was initially maintained steroid‐free on belatacept and belimumab, an inhibitor of B cell activating factor to treat concurrent systemic lupus erythematous; steroids were added subsequently. Renal function, biopsy‐proven rejection, dnDSA, allograft survival, infection, nonadherence, and proteinuria were monitored. Renal function was 86, 73, 52 mL/min/1.73 m2 at 20, 20, and 8 months, respectively. There was 100% adherence to therapy and no development of dnDSA. All patients had treatable infections. One developed steroid‐responsive acute cellular rejection. Belatacept‐based regimens can be tailored for adolescent recipients with good short‐term clinical outcomes.

Induction and maintenance immunosuppression in pediatric kidney transplantation—Advances and controversies

“…The pediatric study of de novo belatacept use reported 10 mg/kg on postoperative days 1, 4, 14, 28, 56, and 84 followed by 5 mg/kg monthly. 125 The pediatric study on conversion to belatacept used similar dosing. 124 The chief concern with belatacept, as illustrated by the BENEFIT A randomized controlled trial of 42 pediatric low-immunologic risk recipients found no difference in the incidence of acute rejection or graft loss but lower incidence of hypertension and hyperlipidemia with steroid withdrawal vs. steroid-inclusive immunosuppression.…”

“…124 A recent retrospective study described the use of belatacept at the time of transplant in three EBV-seropositive adolescents in the setting of induction with alemtuzumab and methylprednisone, and it found 100% adherence and no de novo donorspecific antibody formation. 125…”

Considerations and controversies of pharmacologic management of the pediatric kidney transplant recipient

“…Additional abstracts have been published describing belatacept conversion in six pediatric/AYA KTRs for CNI or mTORi toxicity 138 and in 10 pediatric/AYA KTRs for CNI minimization early posttransplant or withdrawal for CNI toxicity 139 . The most recent publication of belatacept use in adolescent kidney transplantation described patient‐tailored use of belatacept in three patients utilizing a steroid‐free belatacept and sirolimus maintenance regimen with alemtuzumab induction 140 . Conversion from a CNI‐based regimen to a belatacept‐based regimen in adult KTRs has been described by several groups showing improvement in renal function postconversion 141,142 ; such positive results suggest belatacept may be a desirable alternative maintenance agent for adolescent KTRs who would benefit from CNI withdrawal or close medication monitoring during monthly i.v.…”

Role of low-dose calcineurin inhibitor regimens in pediatric kidney transplantation

“…Depletional induction therapy 7 or prolonged use of tacrolimus with gradual wean 8 can reduce the incidence of these rejection episodes. Belatacept‐based therapies in children, albeit limited to case series, 9,10 have demonstrated stabilization in allograft function and utility in the setting of nonadherence. Unfortunately, there is a lack of large pediatric pharmacokinetic studies or trials examining the long‐term risks and benefits of belatacept in children.…”