Use of proliferation signal inhibitors in the management of post-transplant malignancies--clinical guidance

Abstract

Increasing success in renal transplantation and longer patient survival has meant that post-transplant malignancies are having an increasing impact on long-term graft and patient survival. Choice of the immunosuppressive agents provides one of the controllable risk factors for the development of malignancies in this population. Calcineurin inhibitors (CNIs) are associated with an increased incidence of cancers, whereas the proliferation signal inhibitors (PSIs), everolimus and sirolimus have demonstrated anti-oncogenic effects in pre-clinical models and are currently being investigated as anti-cancer agents in clinical trials. There is increasing evidence demonstrating a lower incidence of post-transplant malignancies in renal transplant recipients receiving PSI-based immunosuppression compared with those receiving CNIs. Conversion from CNIs to PSIs has been shown to lead to the regression of Kaposi's sarcoma in renal transplant recipients and is now part of accepted standard care for this tumour in this setting. The anti-cancer properties of PSI-based regimens have the potential to combine the dual benefits of immunosuppression without the use of CNIs and the direct anti-oncogenic effects through their inhibition of the mammalian target of rapamycin (mTOR) signalling pathway. In the absence of formal clinical trial evidence on the best way to use PSIs in this setting, a workshop was held to provide practical guidance on immunosuppressive strategies in the context of malignancy, given the current state of knowledge.