Effects of mTOR-Is on malignancy and survival following renal transplantation: A systematic review and meta-analysis of randomized trials with a minimum follow-up of 24 months

Abstract

BackgroundmTOR-Is positively influence the occurrence and course of certain tumors after solid organ transplantation. The effect of mTOR-Is on the overall incidence of tumors irrespective of their origin is not entirely clear. Furthermore, conflicting data have been shown on mortality under mTOR-Is.MethodsThe current literature was searched for prospective randomized controlled renal transplantation trials. There were 1415 trials screened of which 13 could be included (pts. = 5924). A minimum follow-up of 24 months was mandatory for inclusion. Incidence of malignancies and patient survival was assessed in meta-analyses.ResultsThe average follow-up of all trials was 40.6 months. Malignancy was significantly reduced under mTOR-Is compared to CNIs (RR 0.70, CI 0.49–0.99, p = 0.046). This effect remained stable when combined with CNIs (RR 0.58, CI 0.34–1.00, p = 0.05). When NMSCs were excluded the risk for malignancy remained significantly reduced under mTOR-I therapy (mono and combi) (RR 0.43, CI 0.24–0.77, p = 0.0046). Graft survival was minimally decreased under mTOR-Is (RR 0.99, CI 0.98–1.00, p = 0.054). This effect was abrogated when mTOR-Is were combined with CNIs (RR 0.99, CI 0.97–1.02, p = 0.50). Patient survival was not different (RR 1.00, CI 0.99–1.01, p = 0.54).ConclusionsPosttransplant patients have a lower incidence of malignancy when treated with an mTOR-I no matter if it is used in combination with CNIs or not. This beneficial effect remains significant even when NMSCs are excluded. With currently used mTOR-I-based regimen patient and graft survival is not different compared to CNI therapies.

Infections after kidney transplantation: A comparison of mTOR‐Is and CNIs as basic immunosuppressants. A systematic review and meta‐analysis

“…We did not find a significant difference concerning patient survival between the groups regardless of whether mTOR‐Is were administered with or without a CNI. This confirms the findings of a previous large meta‐analysis and the most recent prospective randomized trials (ZEUS, TRANSFORM, HERAKLES) 44‐47 . However, data have also been published which show a worse survival under mTOR‐Is.…”

Preformed Donor-Specific HLA Antibodies in Living and Deceased Donor Transplantation

“…with cyclosporin A instead of tacrolimus, and lower risk of death-censored graft failure after deceased donation, because cyclosporin A was thought to be less suitable for patients at high risk for allograft rejection (19). A recent meta-analysis of randomized trials, however, showed only marginal differences between calcineurin inhibitor-based regimens and mTOR-inhibitors (20). The more intense initial immunosuppression in patients with DSA (e.g., more induction with ATG and/or rituximab) could have led to increased complications and eventually higher mortality, which would have contributed to the association of DSA with lower overall graft survival.…”

Early conversion to a CNI-free immunosuppression with SRL after renal transplantation—Long-term follow-up of a multicenter trial

“…Benefits of an mTOR-I therapy regarding malignancy have been uniformly confirmed and recently shown to extend beyond skin cancers [27]. Thus, the results from this trial could be expected.…”