Belatacept Combined With Transient Calcineurin Inhibitor Therapy Prevents Rejection and Promotes Improved Long-Term Renal Allograft Function

Abstract

Belatacept, a T cell costimulation-blocker demonstrated superior renal function, lower cardiovascular risk, and improved graft/patient survival in renal transplant recipients. Despite the potential benefits, adoption of belatacept has been limited in part due to concerns regarding higher rates and grades of acute rejection in clinical trials. Since July 2011 we have utilized belatacept-based immunosuppression regimens in clinical practice. In this retrospective analysis of 745 patients undergoing renal transplantation at our center, we compared patients treated with belatacept (n=535) to a historical cohort receiving a tacrolimus-based protocol (n=205). Patient and graft survival were equivalent between all groups. An increased rate of acute rejection was observed in an initial cohort treated with a protocol similar to the low-intensity regimen from the BENEFIT trial vs the historical tacrolimus group (50.5% vs 20.5%). The addition of a transient course tacrolimus reduced rejection rates to acceptable levels (16%). Treatment with belatacept was associated with superior eGFR (belatacept 63.8ml/min vs tacrolimus 46.2ml/min at 4 years, p<0.0001). There were no differences in serious infections including rates of CMV or BK viremia. We describe the development of a costimulatory blockade-based strategy that ultimately allows renal transplant recipients to achieve CNI-free immunosuppression.

Belatacept in renal transplant recipient with mild immunologic risk factor: A pilot prospective study (BELACOR)

“…Patient survival within 12 months after transplant (A) was similar in both groups: death rate in BELACOR group was 0% [0%-7.25%] and in the control group 6.78% [2.88%-15.52%] (P = .07). This result highlights the potential interest already published of an immunosuppressive strategy combining CNIs and belatacept early after transplant (9 months), the high-risk period of acute TCMR, or switching CNIs to belatacept 6 months to 1 year after transplant in order to limit the incidence of T cell-mediated immune events in sensitized recipients and the development of dnDSAs 27. In low-immunological risk kidney allograft recipients, dnDSA incidence is up to 15% within 5 years.…”

“…26 This result highlights the potential interest already published of an immunosuppressive strategy combining CNIs and belatacept early after transplant (9 months), the high-risk period of acute TCMR, or switching CNIs to belatacept 6 months to 1 year after transplant in order to limit the incidence of T cell-mediated immune events in sensitized recipients and the development of dnDSAs. 27 The next remarkable finding was related to the different SAE profile observed in the 2 groups. Patients from the BELACOR group exhibited significantly less infection excluding kidney allograft pyelonephritis and less cardiovascular disorder.…”

“…28 This result is likely to be related to the association of belatacept and depletive induction strategy because the incidence of BK viremia in transplant recipients receiving belatacept and nondepletive induction strategy (basiliximab) was not significantly different than the incidence observed in different control groups treated with CNIs. 27 Such a hypothesis remains to be confirmed by a prospective analysis aiming to compare belatacept and CNIs with polyclonal induction therapy.…”

Alemtuzumab induction and belatacept maintenance in marginal pathology renal allografts

“…One center has recently detailed the evolution of their belatacept use, with their ultimate strategy of belatacept plus transient CNI maintenance yielding a 1 year rejection rate of 16%, decreased from 50.5% upon their initial implementation. 27 When further evaluating the type and grade of rejections seen in our study, it is interesting that there were no AMR episodes in belatacept recipients compared to two episodes in tacrolimus recipients. Belatacept's role in preventing DSA formation has been previously reported, and this effect was maintained in the small study group even when combined with alemtuzumab induction.…”

“…A few studies have previously reported the outcomes of depleting induction in conjunction with belatacept; however, these have been conducted in patients receiving more optimal quality donor kidneys. 19,27,28 While we did not seek to evaluate infectious outcomes, we did have two belatacept-treated patients who had biopsy findings of polyomavirus-associated nephropathy in conjunction with ACR. [24][25][26] Similar to previous literature, belatacept recipients experienced higher grades of rejections, but this did not contribute to short-term graft loss, except in one patient, in whom there were adherence concerns.…”