Long-Term Outcomes after Conversion to a Belatacept-Based Immunosuppression in Kidney Transplant Recipients

Abstract

Background: Conversion to a belatacept-based immunosuppression is currently used as a calcineurin inhibitor (CNI) avoidance strategy when the CNI-based standard-of-care immunosuppression is not tolerated after kidney transplantation. However, there is a lack of evidence on the long-term benefit and safety after conversion to belatacept.

Methods: We prospectively enrolled 311 kidney transplant recipients from 2007 to 2020 from two referral centers, converted from CNI to belatacept after transplant according to a prespecified protocol. Patients were matched at the time of conversion to patients maintained with CNIs, using optimal matching. The primary end point was death-censored allograft survival at 7 years. The secondary end points were patient survival, eGFR, and safety outcomes, including serious viral infections, immune-related complications, antibody-mediated rejection, T-cell-mediated rejection, de novo anti-HLA donor-specific antibody, de novo diabetes, cardiovascular events, and oncologic complications.

Results: A total of 243 patients converted to belatacept (belatacept group) were matched to 243 patients maintained on CNIs (CNI control group). All recipient, transplant, functional, histologic, and immunologic parameters were well balanced between the two groups with a standardized mean difference below 0.05. At 7 years post-conversion to belatacept, allograft survival was 78% compared with 63% in the CNI control group ( P < 0.001 for log-rank test). The safety outcomes showed a similar rate of patient death (28% in the belatacept group versus 36% in the CNI control group), active antibody-mediated rejection (6% versus 7%), T-cell-mediated rejection (4% versus 4%), major adverse cardiovascular events, and cancer occurrence (9% versus 11%). A significantly higher rate of de novo proteinuria was observed in the belatacept group as compared with the CNI control group (37% versus 21%, P < 0.001).

Conclusions: This real-world evidence study shows that conversion to belatacept post-transplant was associated with lower risk of graft failure and acceptable safety outcomes compared with patients maintained on CNIs.

Clinical trial registry name and registration number: Long-term Outcomes after Conversion to Belatacept, NCT04733131 .

Graphical abstract

Figure 1

Study flowchart. The included patients from the belatacept conversion cohort (kidney transplant recipients from Necker and Saint-Louis hospitals converted from CNI to belatacept after transplant since 2007) are in red. The included patients from the CNI maintenance cohort (kidney transplant recipients from Necker and Saint-Louis hospitals between 2004 and 2019) are in blue. *Performed at the same time during the kidney allograft evaluation under a CNI-based immunosuppression. ah, arteriolar hyalinosis; CNI, calcineurin inhibitor; cv, vascular fibrous intimal thickening; DGF, delayed graft function; DSA, circulating anti-HLA donor-specific antibody; IFTA, interstitial fibrosis and tubular atrophy.

Figure 2

Death-censored allograft survival up to 7 years between patients converted to belatacept after kidney transplantation at the time of conversion for CNI intolerance and matched control patients maintained under a calcineurin inhibitors-based immunosuppression. The blue line is the death-censored allograft survival of the matched patients from the CNI maintenance cohort, and the red line is the death-censored allograft survival of the matched patients from the belatacept conversion cohort. P value is obtained from the log-rank test.