Minimizing the risk of cancer in transplant patients

Recent improvements in immunosuppressive therapies have reduced the incidence of acute rejection and increased patient survival. These agents may however contribute to higher rates of mortality due to an increased risk of cardiovascular disease or malignancy. Transplant patients are in an immunocompromised state, and have a reduced ability to combat the development of malignancy. The higher risk for the activity of oncoviruses may also contribute to the higher incidence and the specific tumor types seen. Some immunosuppressants may have a direct oncogenic effect. In vitro data have demonstrated that calcineurin inhibitors (CNIs) may have a direct effect on tumor growth and the development of metastases. In contrast, mTOR inhibitors have demonstrated in vitro antitumoral properties, perhaps via a potent antiangiogenic effect. Recent studies and registry analyses have confirmed that mTOR inhibitors are associated with a reduced incidence of malignancies. UNOS data demonstrated that an mTOR inhibitor, with or without a CNI, is associated with a reduced incidence of cancer compared to regimens without mTOR inhibitors. The Rapamune Maintenance Regimen study demonstrated that patients receiving sirolimus-based, CNI-free therapy after CsA withdrawal at 3 months had a reduced incidence of malignancy at 5 years post-transplant compared with those who continued a regimen including CsA. In the CONVERT study, patients converted to sirolimus had significantly lower malignancy rates (3.1%) at 24 months compared with those who continued CNI-based therapy (9.8%, p<0.001). The elimination of CNIs and the introduction of sirolimus may therefore have a role in reducing the risk of cancer in post-transplant patients.