Increased CMV disease and "severe" BK viremia with belatacept vs. sirolimus three-drug maintenance immunosuppression

Objectives: Belatacept may provide benefit in delayed graft function, but its association with infectious complications is understudied. We aim to assess the incidence of CMV and BK viremia in patients treated with sirolimus or belatacept as part of a three-drug immunosuppression regimen after kidney transplantation.

Materials and methods: Kidney transplant recipients from 01/01/2015 to 10/01/2021 were retrospectively reviewed. Maintenance immunosuppression was either tacrolimus, mycophenolate and sirolimus (B0) or tacrolimus, mycophenolate, and belatacept (5.0 mg/kg monthly) (B1). Primary outcomes of interest were BK and CMV viremia which were followed until the end of the study period. Secondary outcomes included graft function (serum creatinine, eGFR) and acute rejection through 12 months.

Results: Belatacept was initiated in patients with a higher mean kidney donor profile index (B0:0.36 vs. B1:0.44, p = .02) with more delayed graft function (B0:6.1% vs. B1:26.1%, p < .001). Belatacept therapy was associated with more "severe" CMV viremia >25,000 copies/mL (B0:1.2% vs. B1:5.9%, p = .016) and CMV disease (B0:0.41% vs. B1:4.2%, p = .015). However, there was no difference in the overall incidence of CMV viremia >200 IU/mL (B0:9.4% vs. B1:13.5%, p = .28). There was no difference in the incidence of BK viremia >200 IU/mL (B0:29.7% vs. B1:31.1%, p = .78) or BK-associated nephropathy (B0:2.4% vs. B1:1.7%, p = .58), but belatacept was associated with "severe" BK viremia, defined as >10,000 IU/mL (B0:13.0% vs. B1:21.8%, p = .03). The mean serum Cr was significantly higher with belatacept therapy at 1-year follow up (B0:1.24 mg/dL vs. B1:1.43 mg/dL, p = .003). Biopsy-proven acute rejection (B0:1.2% vs. B1:2.6%, p = .35) and graft loss (B0:1.2% vs. B1:0.84%, p = .81) were comparable at 12 months.

Conclusions: Belatacept therapy was associated with an increased risk of CMV disease and "severe" CMV and BK viremia. However, this regimen did not increase the overall incidence of infection and facilitated comparable acute rejection and graft loss at 12-month follow up.

 

Comments:

The objective of the study was to assess the incidence of cytomegalovirus (CMV) and BK virus (BKV) viremia in kidney transplant recipients treated with sirolimus or belatacept as part of a three-drug immunosuppression regimen. The study retrospectively reviewed kidney transplant recipients from January 1, 2015, to October 1, 2021.

The maintenance immunosuppression regimens evaluated were either tacrolimus, mycophenolate, and sirolimus (referred to as B0) or tacrolimus, mycophenolate, and belatacept (5.0 mg/kg monthly) (referred to as B1).

The primary outcomes of interest were the incidence of BKV and CMV viremia, which were followed until the end of the study period. Secondary outcomes included graft function (measured by serum creatinine and estimated glomerular filtration rate) and acute rejection within 12 months.

The results showed that patients receiving belatacept had a higher mean kidney donor profile index compared to those receiving sirolimus (B0: 0.36 vs. B1: 0.44, p = .02). Additionally, belatacept therapy was associated with a higher incidence of delayed graft function (B0: 6.1% vs. B1: 26.1%, p < .001).

Regarding viral infections, belatacept therapy was associated with a higher incidence of "severe" CMV viremia (>25,000 copies/mL) (B0: 1.2% vs. B1: 5.9%, p = .016) and CMV disease (B0: 0.41% vs. B1: 4.2%, p = .015). However, there was no significant difference in the overall incidence of CMV viremia (>200 IU/mL) between the two groups (B0: 9.4% vs. B1: 13.5%, p = .28).

Regarding BKV, there was no significant difference in the incidence of BK viremia (>200 IU/mL) (B0: 29.7% vs. B1: 31.1%, p = .78) or BK-associated nephropathy (B0: 2.4% vs. B1: 1.7%, p = .58). However, belatacept therapy was associated with a higher incidence of "severe" BK viremia (>10,000 IU/mL) (B0: 13.0% vs. B1: 21.8%, p = .03).

At 1-year follow-up, patients receiving belatacept had a significantly higher mean serum creatinine compared to those receiving sirolimus (B0: 1.24 mg/dL vs. B1: 1.43 mg/dL, p = .003). The rates of biopsy-proven acute rejection (B0: 1.2% vs. B1: 2.6%, p = .35) and graft loss (B0: 1.2% vs. B1: 0.84%, p = .81) were comparable between the two groups at 12 months.

In conclusion, belatacept therapy was associated with an increased risk of CMV disease and "severe" CMV and BK viremia. However, it did not significantly increase the overall incidence of infection and showed comparable rates of acute rejection and graft loss compared to sirolimus therapy at the 12-month follow-up.