Alemtuzumab induction therapy in solid organ transplantation

摘要

Alemtuzumab (Campath) is a monoclonal antibody that has a profound lymphocyte-depleting effect, targeting the CD52 antigen that is present on all lymphocytes. Alemtuzumab has been used for the treatment of chronic lymphocytic leukaemia and various autoimmune disorders, and has also shown potential as an induction agent in the prevention of rejection following solid organ transplantation. Alemtuzumab has been studied in randomised controlled trials and has demonstrated low levels of rejection in renal transplant recipients compared with other induction agents, albeit mainly in the early months following transplantation. Studies have shown that alemtuzumab enables the use of lower calcineurin inhibitor (CNI) maintenance drugs; however, this reduction in nephrotoxic immunosuppression has not consistently been matched by an improvement in renal function. The hypothesis has been suggested that alemtuzumab might allow the development of immunosuppressive regimens that avoid CNIs completely; studies have investigated the combination of alemtuzumab with mammalian target of rapamycin-inhibitor maintenance therapy, and, in particular, sirolimus. Initial studies with this combination showed that regimens of sirolimus alone and of sirolimus with mycophenolate mofetil were unsuccessful, with a high rate of rejection and complications. Subsequent studies have targeted the combination of alemtuzumab induction with a short course of a CNI, before switching to maintenance therapy with sirolimus. This regimen might combine good protection from acute cellular rejection and chronic nephrotoxicity. A randomised controlled trial has been established to study this regimen, with results pending.