Long-Term Exposure to Belatacept in Recipients of Extended Criteria Donor Kidneys

Abstract

Patients in the BENEFIT-EXT study received extended criteria donor kidneys and a more intensive (MI) or less intensive (LI) belatacept immunosuppression regimen, or cyclosporine A (CsA). Patients who remained on assigned therapy through year 3 were eligible to enter a long-term extension (LTE) study. Three hundred four patients entered the LTE (n ¼ 104 MI; n ¼ 113 LI; n ¼ 87 CsA), and 260 continued treatment through year 5 (n ¼ 91 MI; n ¼ 100 LI; n ¼ 69 CsA). Twenty patients died during the LTE (n ¼ 5 MI; n ¼ 9 LI; n ¼ 6 CsA), and eight experienced graft loss (n ¼ 2 MI; n ¼ 1 LI; n ¼ 5 CsA). Three patients experienced an acute rejection episode (n ¼ 2 MI; n ¼ 1 LI). The incidence rate of serious adverse events, viral infections and fungal infections was similar across groups during the LTE. There were four cases of posttransplant lymphoproliferative disorder (PTLD) from the beginning of the LTE to year 5 (n ¼ 3 LI; n ¼ 1 CsA); two of three PTLD cases in the LI group were in patients who were seronegative for Epstein-Barr virus (EBV(À)) at transplantation. Mean AE SD calculated GFR at year 5 was 55.9 AE 17.5 (MI), 59.0 AE 29.1 (LI) and 44.6 AE 16.4 (CsA) mL/min/ 1.73 m 2 . Continued treatment with belatacept was associated with a consistent safety profile and sustained improvement in renal function versus CsA over time.

Long-Term Outcomes in Belatacept- Versus Cyclosporine-Treated Recipients of Extended Criteria Donor Kidneys: Final Results From BENEFIT-EXT, a Phase III Randomized Study

“…As in prior analyses 28, 29, 30, acute rejection was defined as central biopsy–proven rejection that was either clinically suspected for protocol‐defined reasons or clinically suspected for other reasons and treated. A combined end point comprising time to first occurrence of death, graft loss or estimated GFR (eGFR) <20 mL/min per 1.73 m 2 was examined post hoc .…”

“…The statistical approaches used in this 7‐year analysis differ from those used at 1, 3, and 5 years after transplant 28, 29, 30. First, in the present report, all evaluable patients were analyzed per the intent‐to‐treat principle; evaluable patients were alive and observable at 84 mo after randomization or died or experienced graft loss by month 84.…”

“…First, in the present report, all evaluable patients were analyzed per the intent‐to‐treat principle; evaluable patients were alive and observable at 84 mo after randomization or died or experienced graft loss by month 84. Similarly, the intent‐to‐treat population was analyzed at 1 and 3 years after transplant 28, 29, whereas a subgroup of patients corresponding to the long‐term extension cohort was analyzed at 5 years after transplant 30. The long‐term extension cohort represented a subset of the intent‐to‐treat population because it was composed of only those patients who completed 36 mo of study treatment and consented to continue the study beyond month 36 30.…”

“…Similarly, the intent‐to‐treat population was analyzed at 1 and 3 years after transplant 28, 29, whereas a subgroup of patients corresponding to the long‐term extension cohort was analyzed at 5 years after transplant 30. The long‐term extension cohort represented a subset of the intent‐to‐treat population because it was composed of only those patients who completed 36 mo of study treatment and consented to continue the study beyond month 36 30. Second, rates of death and/or graft loss were presented as point estimates at 1 and 3 years after transplant 28, 29, but in the present analysis, the Kaplan–Meier method was used to derive estimated rates of death and/or graft loss.…”

“…These randomized phase III studies compared two belatacept‐based immunosuppressive regimens (more intense [MI] and less intense [LI]) with CsA‐based immunosuppression in adult kidney transplant recipients. In BENEFIT‐EXT, analyses performed at 1, 3 and 5 years after transplant demonstrated that belatacept‐based immunosuppression was associated with similar rates of patient and graft survival and superior renal function versus CsA‐based immunosuppression; however, rates of acute rejection were numerically higher with belatacept‐based treatment 28, 29, 30.…”