Background: Chronic antibody mediated rejection (cAMR) is a major cause of long-term kidney transplant (KT) loss. Antibody or immune cell depletional therapies have unclear efficacy with significant side effects. We have previously reported safe conversion from tacrolimus (TAC) to belatacept (bela) in sensitized patients with chronic interstitial fibrosis/tubular atrophy (IFTA) with a prior history of acute AMR. In this study we explored the safety and efficacy of bela conversion in patients with cAMR+IFTA.

Methods: Adult KTs with allograft dysfunction and biopsy-proven cAMR+IFTA, were converted to bela with a TAC taper over 12 weeks. Mycophenolate was maximized to 2-3g/d as tolerated. All patients underwent a surveillance biopsy after 6-10 months of conversion. Both pre- and post-conversion biopsies underwent transcriptome analysis using the MMDx platform. An arbitrary eGFR improvement of >5ml/min/m2 was defined as 'clinical response (CR)'.

Results: Eleven KTs (mean age=45 years) were converted from TAC to bela at a median of 36 months post-KT. A majority of patients were African-American (64%), regrafts (45%), and sensitized (mean cPRA=38%). At a median follow-up of 14 months post-conversion, renal function trended towards improvement from a mean eGFR of 32±11 ml/min/1.73m2 to 36±12 ml/min/1.73m2 (p=0.2) while proteinuria remained unchanged (1.7±1.8 mg/mg vs 2.0±1.4 mg/mg; p=0.8). At most recent follow-up, there were no cases of acute rejection with a graft and patient survival of 100%. Overall, neither histologic or transcriptome analysis showed any significant differences between pre- and post-conversion biopsies. Five (45%) patients showed CR. Of these five, 2 (18%) had significant histologic and molecular improvement. Molecular analysis suggested that patients with lower rejection and injury scores on pre-conversion biopsies had a higher likelihood of CR, suggesting that response might depend on less severe disease activity and tissue injury.

Conclusions: In this first early experience, we report that belatacept might result in improved kidney function in at least a subset of patients with cAMR who were not subjected to intensive traditional therapies. It is possible that TAC-associated vasoconstrictive injury potentiates immune injury. Future studies might help in risk-stratification to individualize therapy.

CITATION INFORMATION: Kumar D, Gupta G, Reeve J, Sanghi P, Bobba S, Levy M, Bhati C, Kimball P, Fattah H, King A, Massey H, Halloran P. Belatacept for Chronic Antibody-Mediated Rejection in Kidney Transplantation. Am J Transplant. 2017;17 (suppl 3).

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