Extended Experience of Belatacept Conversion in Kidney Transplant Patients with Chronic Active Antibody-Mediated Rejection

Background: Chronic active antibody mediated rejection (cABMR) is a major cause of kidney transplant (KT) loss. Current therapies have unclear efficacy and side effects. We have previously presented our experience with belatacept conversion with an improved eGFR compared to propensity matched controls (Kumar et al, Transplantation 2021). Here we present our extended experience with clinical outcomes and graft survival. Methods: 55 patients with biopsy-proven cABMR were converted to belatacept with a modified tacrolimus taper performed over 12 weeks. 46/55 (84%) patients underwent biopsies between 6-12 months post-conversion and 32/55 (58%) also underwent paired transcriptome analysis using the molecular microscope (MMDx; ATAGC). We followed eGFR, graft survival and evaluated predictors of graft survival. Results: Patients (mean age: 44years) were converted from tacrolimus to belatacept at a median of 29 months post-KT. At conversion, the cohort had low mean GFR of 44.6±22ml/min/1.73m2 and high mean chronicity scores (CI+CT) of 2.55±1.31. The mean decline in eGFR for the 12 months prior to conversion was -0.89±2.5ml/min/1.73m2 which then stabilized/improved to 1.37±2.9 ml/min/1.73m2 (p=0.002) 12 months after conversion. 53/55 (96%) of patients had less than 30% decline in GFR at 12-months. A paired histologic and MMDx comparison of pre and post-biopsies showed no worsening in microvascular inflammation (G+PTC), chronicity scores (CI+CT) and molecular ABMR scores. Overall, at a median follow up of 58 months (IQR:39-66), death censored graft survival was 67% and patient survival was 87%. Those with graft loss had a significantly lower GFR at conversion (36±16ml/min/1.73m2 vs 49±23ml/min/1.73m2; p=0.03). The area under the curve (AUC) for GFR at conversion was 0.69 (95% [CI] 0.55 to 0.80; p=0.01) for predicting graft failure. A GFR cutoff value of less than 30ml/min/1.73m2 had a specificity of 76% and sensitivity of 55%. Conclusion: In this largest and extended report on belatacept conversion for cABMR with associated low GFR and high chronicity in patients who were otherwise not candidates for additional intensive immunosuppressive therapies, showed both short and long-term stability in renal function. Extended graft survival was seen in patients who had higher GFR at the time of conversion.