Immunosuppression Strategies Including the Use of Belatacept, mTOR Inhibitors and Steroid-Sparing Protocols

Abstract Purpose of Review Maintenance immunosuppression for pancreas transplantation has been largely derived from kidney transplant practice. The combination of a calcineurin inhibitor (CNI), mycophenolate and corticosteroids remains the backbone of immunosuppression in pancreas transplantation. Although this regimen achieves very low rejection rates and excellent short-term survival, progressive CNI-induced nephrotoxicity, β-cell injury, and cardiovascular and metabolic adverse effects carry significant long-term consequences among pancreas transplant recipients. This review examines the utility of CNI withdrawal or minimization by utilizing belatacept and/or mammalian target of rapamycin (mTOR) inhibitors, and the utility of steroid-sparing regimens in pancreas transplantation. Recent Findings Belatacept is associated with an increased risk of acute rejection when used in the setting of CNI withdrawal but can be effective when added to a low-dose CNI regimen. Late conversion while maintaining a low-dose CNI is associated with better allograft survival and lower rejection rates. Steroid withdrawal can be successful in the low immunologic risk population when paired with effective adjunct maintenance immunosuppression. mTOR inhibitors are associated with higher drug intolerance but may confer benefits depending on the timing, immunologic risk and infection status. Summary Outcomes are determined by the immunosuppression that remains rather than the agent that was withdrawn. Pancreas allograft survival is impacted by the occurrence and severity of rejection regardless of the combination of immunosuppression that is utilized. An individualized approach guided by transplant type, immunologic risk, timing of intervention, and cardiometabolic and infectious risks is of utmost importance in managing immunosuppression among pancreas transplant recipients.