*Purpose: We investigated the outcomes of mammalian target of rapamycin inhibitor (MTORI) regimens in adult kidney transplant (KT) recipients (KTRs) in categories of donor/recipient pre-transplant HLA mismatch (mm).

*Methods: Using SRTR data, we compared the 5-yr. maximum follow-up risks of solid-organ malignancy, lymphoma, and non-melanoma skin cancer (NMSC) associated with 1st transplant-yr. immunosuppression with MTORI [sirolimus or everolimus combined with either a calcineurin inhibitor (CNI), mycophenolate, or azathioprine) and non-MTORI (any CNI, mycophenolate, or azathioprine combination) regimens in adult-KTRs in the 0, 1-3, and 4-6 HLA mm groups.

*Results: Probability of lymphoma-free survival did not differ between KTRs on MTOR-I and non-MTOR-I regimens regardless of their HLA mm category (Fig 1). Solid organ malignancy (SOM)-free and NMSC-free 5-year survival probabilities were higher with m-TOR-I vs. non-MTOR-I regimens in virtually all HLA mm categories (Figs. 1 and 2, respectively). The relative risk (RR) for lymphoma was lower with MTOR-I vs. non-MTOR-I regimens only in one (the 1-3) HLA mm category (Fig. 3). However, the RRs for SOM and NMSC were lower with MTOR-I regimens in all HLA mm categories. Furthermore, we observed more reductions of risks associated with MTOR-I regimens from SOM in KTRs with 4-6 (vs. 0) HLA mm and NMSC in KTRs with 1-3 and 4-6 (vs. 0) HLA mm (Fig. 3).

*Conclusions: The relationship between MTOR-I regimen and HLA mm should be re-examined with the aim of reducing post-KT malignancy events through risk-based immunosuppression selection.

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