Real-world evidence regarding cancer, mortality, and graft failure risk with de novo belatacept use among kidney transplant recipients in the United States.

Belatacept is a selective T-cell co-stimulation blocker used in maintenance immunosuppression for kidney transplant recipients (KTRs), but evidence on cancer risk and other outcomes is limited. This retrospective cohort study used linked US transplant and cancer registry data on KTRs treated with belatacept (N=1514) or tacrolimus (N=7570) as initial maintenance therapy. We used multivariable Cox regression models to compare incidence of invasive cancer, cutaneous squamous cell carcinoma (cSCC), posttransplant lymphoproliferative disorder (PTLD), death, and graft failure/retransplantation (GF/RT) between belatacept and tacrolimus users. Overall, cancer incidence was 10.1 and 12.6 per 1000 person-years in belatacept and tacrolimus users, respectively. We did not find increased risk with belatacept for cancer overall (adjusted hazard ratio [HR] 0.83, 95% confidence interval [95%CI] 0.53-1.30), individual cancer types, or cSCC. Belatacept was associated with increased risk of death (adjusted HR 1.22, 95%CI 1.04-1.43) but lower risk of GF/RT more than four years after transplantation (0.54, 0.35-0.83). PTLD risk was increased among EBV-seropositive KTRs (adjusted HR 1.96, 95%CI 1.03-3.73). This study provides reassurance that belatacept does not increase cancer risk among KTRs, and there was a long-term protective association for GF/RT. However, we found evidence suggesting a potential increased risk of PTLD and death with belatacept use.