498 - Once-Daily Mammalian Target of Rapamycin Inhibition as an Alternative to Mycophenolic Acid in High-Risk Pediatric Kidney Transplant Recipients on Belatacept

Publication Number: 2484.498

Abigail M. Schnaith, Emory University School of Medicine, Atlanta, GA, United States; Meredith T. Combs, Children's Healthcare of Atlanta, Atlanta, GA, United States; Brittney Grabowski, Children's Healthcare of Atlanta, Atlanta, GA, United States; Robert Achram, Emory University School of Medicine, Atlanta, GA, United States; Jackson Londeree, Emory University School of Medicine, Atlanta, GA, United States; Carissa Hayes, Children's Healthcare of Atlanta, Atlanta, GA, United States; Elizabeth LaHaie, Children's Healthcare of Atlanta, Brookhaven, GA, United States; Roshan George, Emory University & Children's Healthcare of Atlanta of Atlanta, Atlanta, GA, United States; Rouba Garro, Emory University School of Medicine, Atlanta, GA, United States

Background: Belatacept (bela) is a co-stimulatory blocker that minimizes calcineurin inhibitor nephrotoxicity and is especially beneficial in patients for which there are concerns about medication non-adherence. Standard bela regimen includes twice-daily mycophenolate mofetil (MMF) and prednisone (pred), but many adolescents struggle with twice-daily dosing schedules. Daily dosed rapamycin (rapa) represents a reasonable alternative to MMF in this high-risk population because it reduces pill burden and may offer synergetic immunosuppressive effects when combined with bela. A combination of bela, and rapa has previously been reported in only two pediatric patients.

Objective: To describe the indications, safety, and efficacy of a bela and rapa immunosuppression regimen in high-risk pediatric kidney transplant recipients (KTRs).

Design/Methods: This retrospective case series includes five pediatric KTRs receiving bela who were transitioned from MMF to rapa between 1/1/2020-10/1/2025. Clinical characteristics including age, sex, transplant date, type of transplant, induction and maintenance immunosuppression, side effects, and therapeutic drug levels were collected. Indications for switching to bela/rapa/pred were recorded. Outcomes were assessed by biopsy- proven rejection, changes in CKiD U25 estimated glomerular filtration rate (eGFR), and changes in highest donor-specific antibody (DSA) median fluorescence intensity (MFI) following conversion.

Results: Five male patients ages 15 to 21 years were converted from bela/MMF/pred to bela/rapa/pred a median of 2.92 years post-transplant (IQR 1.38-10.05). All patients received 5mg pred daily and a mean bela dose of 5.1mg/kg/dose (sd. 0.08). Mean rapa dose was 3.2mg daily (sd. 1.3) with a mean rapa trough of 8.92ng/mL (sd 2.70; target 6-8ng/mL) over the first 6 months. Four of five patients converted to bela/rapa/pred due to ongoing non-adherence concerns and recurrent episodes of rejection; three had DSA prior to conversion. After conversion, only patient 2 experienced biopsy - proven rejection, which occurred in the context of undetectable rapa levels beginning 6 months after the switch. All other patients had relatively stable eGFR and DSA levels (Figure 1 and Figure 2). Rapa side effects including proteinuria and dyslipidemia were not observed. No viral or bacterial infections were observed during follow-up.

Conclusion(s):

Conclusion: Once-daily rapamycin in combination with belatacept may be a safe and effective immunosuppressive strategy for high-risk pediatric KTRs with adherence challenges and should be considered in this population.

Figure 1
The eGFR trends after conversion to rapa.

Figure 2
The donor specific antibody MFI trends 1 year post conversion to rapa.