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.

Sebastian Wolf,Jens Werner,Verena S Hoffmann,Markus Schoenberg,Julian Bucher,Markus Guba,Joachim Andrassy,Antje Habicht,Teresa Kauke

doi:10.1371/journal.pone.0194975

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.

Highlights

The number of transplants and the alive transplant population is growing
Malignancy was significantly reduced under mTOR-Is compared to CNIs (RR 0.70, CI 0.49–0.99, p = 0.046)
When non-melanoma skin cancer (NMSC) were excluded the risk for malignancy remained significantly reduced under mTOR-I therapy (RR 0.43, CI 0.24–0.77, p = 0.0046)

Summary

Introduction

In the US, an increase of 9.2% was encountered for annually performed transplants from 2010 to 2015 (OPTN data). This has implications for the medical system. According to an USRDS based analysis around 15.6% of renal transplant recipients are expected to die within the first three years after renal transplantation, of these 76.3% with a functioning graft representing 46.8% of all graft losses [1]. Most of these patients die of cardiovascular problems, followed by infections and malignancy. Conflicting data have been shown on mortality under mTOR-Is

Methods

Results

Conclusion