Organ transplant recipients (OTR) have a reported 3-4 fold increased incidence of malignancy as compared to the general population. Malignancy has been associated with the necessary immunosuppressive medications used. Recent studies have shown that inhibitors of the mammalian target of rapamycin (mTOR-I), including sirolimus and everolimus have antineoplastic properties yet few studies have assessed their effectiveness in preventing malignancies in OTRs. A 12-year retrospective cohort study of OTRs with a first malignancy was conducted to compare the risk of second malignancy in those exposed to mTOR-I (n=144) versus those not exposed to mTOR-I (n=48). Total cumulative dose of immunosuppressive medications prescribed and pathology proven malignancies were recorded using electronic medical records. Cox proportional hazards models were used to calculate hazard ratios (HR) for the risk of second malignancy associated with immunosuppressive medications. The most common second malignancy was non-melanoma skin cancer (72%). The mean cumulative dose of mTOR-I was higher in those who did not form a second malignancy (Wilcoxon rank-sum p<0.001). Furthermore, any use of mTOR-I after the diagnosis of a first malignancy was associated with a lower risk of a second malignancy regardless of cumulative dose of other immunosuppressive drugs (HR 0.37 [CI 0.24-0.57], p<0.001). The results suggest that mTOR-I have an antitumoral effect among OTRs with a previous malignancy. Thus, conversion to an mTOR-I regimen may be considered in OTRs who develop malignancy.

Karia, P.: Grant/Research Support, mTOR Inhibitors. Azzi, J.: Grant/Research Support, mTOR Inhibitors. Heher, E.: Grant/Research Support, mTOR Inhibitors. Schmults, C.: Grant/Research Support, mTOR Inhibitors.

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