Experience of Utilizing Low-Dosage Belatacept and Cyclosporine in Patients with Refractory BK Polyoma Viremia

Background: There are no proven therapeutic options for BK polyoma virus (BKPyV) nephropathy apart from immunosuppression reduction. In-vitro studies have shown that tacrolimus (FK) promotes BKPyV replication through FK binding protein-12 pathyway, while cyclosporine (CsA) inhibits BKPyV replication. Belatacept, CD80/86-CD28 co-stimulation blocker, may have theoretical benefits by avoiding calcineurin inhibitor related nephrotoxicity and FKBP-12 mediated BKPyV replication. We present our experience of CsA and low dose belatacept in refractory BKPyV viremia on FK-based immunosuppression. Methods: 15 adult kidney transplant patients with refractory BKPyV viremia despite reduction in immunosuppression and IVIg were included. Patients with worsening eGFR were switched to low dose belatacept 2.5mg/kg every 2 weeks for first 5 doses, then monthly (BELA group) and ones with stable eGFR were converted to CsA (CsA group). eGFR and BKPyV PCR between the groups were compared at 3- and 6-months post conversion. Results: 10/15(67%) patients were in BELA group and 5(33%) were in CsA group. BELA group was transitioned to belatacept at 6+3 months after diagnosis. Mean FK trough was 7.5+2.8ng/ml and median daily dose of mycophenolate(MMF) was 0 mg (range 0-500 mg) at conversion. Mean follow up was 34+19 months. Mean eGFR improved from 24.7+8.3 to 30.4+7.5(p=0.01) at 6 months. BKPyV viral load improved from a median of 87100 COPIES/ml (range 5290-1880000) to 2055 COPIES/ml (range 0-26000;p=0.08). 6/10(60%) patients had resolution of viremia. CsA group were switched to CsA at 21+10 months after diagnosis. Mean FK trough was 6.1+0.6ng/ml and patients were off MMF at the start of CsA. Mean follow up was 13.8+3.3 months. Mean eGFR remained stable, 55+12.5 at conversion vs 54.4+10.7 at 6 months. BKPyV viral load at 6-month improved from a median of 61500 COPIES/ml (range 11500-94800) to 4130 COPIES/ml (range1100-6460;p=0.08). 3/5(60%) patients had resolution of viremia. No rejection was reported in either group. Conclusion: In our experience, there was a significant reduction in BKPyV viral loads with both strategies. The kidney function improved with belatacept conversion and it remained stable with CsA conversion. Longer follow up is needed to understand the graft outcomes with these strategies. These results provide a framework for prospective studies.