*Purpose: 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 trend with propensity matched controls (Kumar et al, Transplantation 2021). Here we present our extended experience with additional patients and report clinical predictors of response to belatacept conversion.

*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 post-conversion biopsies between 6-12 months post-conversion and 32/55 (58%) also underwent paired transcriptome analysis using the molecular microscope (MMDx; ATAGC). We defined a ‘response to therapy’ as a change in (negative) slope of eGFR from 12 months prior to conversion to a positive slope after conversion.

*Results: Patients (mean age: 44years) were converted from tacrolimus to belatacept at a median of 29 months post-KT. For the overall cohort, renal function remained stable with a mean eGFR of 45±22ml/min/1.73m2 to 48±30ml/min/1.73m2 (p=0.50) at a median follow-up of 21 months (range=3.4-56) post-conversion. There were no new cases of acute rejection with a death-censored graft and patient survival of 85% and 93%, respectively. The average decline in eGFR from 12 months prior to conversion was -0.89±2.5ml/min/1.73m2 that stabilized and improved to 0.35±1.2 ml/min/1.73m2 (p=0.003) over 12 months post conversion. A paired histologic comparison and MMDx comparison of pre and post-conversion biopsies showed no worsening in microvascular inflammation (G+PTC), chronicity scores (CI+CT) and molecular ABMR scores. 35/55 (64%) patients had an obvious improvement in the slope of eGFR for the 12 months after conversion. Using a multivariate logistical regression model, the predictors of response to therapy included less interstitial fibrosis and tubular atrophy (IFTA; CI+CT) (OR: 0.54; 95% CI [0.30, 0.98]; p=0.03) and a higher eGFR (OR: 1.06; 95% CI [1.01, 1.1]; p=0.001) at the time of conversion.

*Conclusions: In this extended report, we find that belatacept conversion in patients with cABMR not recently subjected to intensive immunosuppressive therapies continued to result in long-term stability in renal function. Response to therapy was best seen among patients that underwent early conversion, as evidenced by better kidney function and less IFTA at the time of initial diagnosis.

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