Use of proliferation signal inhibitors in the management of post-transplant malignancies—clinical guidance
1Servei de Nefrologia I Transplantament Renal, Renal Transplant Unit, Hospital Clinic, Universitat de Barcelona, 170, Villarroel, 2Jefe de Servico, Servico de Oncología Médica, Hospital del Mar-IMAS, Paseo Maritimo 25-29, Barcelona 08003, Spain, 3Cologne General Hospital, Merheim Medical Centre, Koeln-Merheim, Germany, 4Department of Nephrology and Transplantation, Laiko Hospital, Athens, Greece, 5ITERT, Department of Nephrology and Clinical Immunology, 30 Bd Jean Monnet, CHU Nantes, 44093 Nantes, Cedex 01, France, 6Department of Nephrology, Leiden University Medical Center, NL-2333ZA Leiden, The Netherlands, 7Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, 8University Clinic Charité, Campus Charité Mitte, Department of Nephrology, Berlin, Germany, 9Surgical Department, Rikshospitalet University Hospital, Oslo, Norway, 10Servicio de Nefrología, Hospital Ramón y Cajal, Madrid, Spain, 11Division of Nephrology and Dialysis, Internal Medicine III, Medizinische Universität Wien, Vienna, Austria, 12Division of Nephrology Dialysis and Transplantation, Policlinico, 70124 Bari, Italy, 13Nephrology Department, Hospital Universitario de Bellvitge, Barcelona, Spain, 14Renal Unit, Kidney Transplantation Center, ‘Leonardo Sciascia’ Civic Hospital, Palermo, Italy and 15Director of Renal and Urology, University of Sydney, Westmead Hospital, Westmead, NSW, Australia
Correspondence and offprint requests to: J. R. Chapman, Renal Unit, Westmead Hospital, Westmead, NSW 2145, Australia. Tel: +61 2 9845 6349; Fax: +61 2 9845 8300; Email: Jeremy_Chapman{at}wsahs.nsw.gov.au
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Abstract |
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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.
Keywords: immunosuppression; malignancy; proliferation signal inhibitors/mTOR inhibitors; renal transplant
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