Immunosuppressive Treatment With mTOR Inhibitors for Malignancies After Liver Transplantation: Long-Term Survival Retrospective Analysis

Transplant Proc. 2020 Jun;52(5):1507-1510. doi: 10.1016/j.transproceed.2020.02.058. Epub 2020 Mar 22.

Abstract

Background: Immunosuppressive calcineurin inhibitors have been associated with an increased risk of post-transplant malignancies. The mammalian target of rapamycin inhibitors (mTORi) is an alternative immunosuppressive regimen with an antineoplastic effect. The aim of the study was to determine the long-term survival of mTORi-treated recipients with de novo or recurring tumors after liver transplantation (LT).

Methods: This retrospective analysis included mTORi-treated LT recipients between March 2013 and March 2019. We analyzed long-term survival and mTORi indications in an oncology setting in patients with de novo and recurrent malignancies after LT. Overall survival (OS) rate was compared from the Spanish Liver Transplant Registry (SLTR) data using the Kaplan-Meier method. High-risk hepatocellular carcinoma (HCC) was defined as microvascular invasion or satellite lesions as described in the liver explant.

Results: A total of 237 patients underwent LT during the study period; 111 patients underwent mTORi-based immunosuppression (48%, cancer was the main indication): 24.5% high-risk HCC; 24.4% HCC recurrence; 14.3% cholangiocarcinoma; and 36.7% de novo malignancies. The 1- and 5-year OS rates after LT in the mTORi group were 83% and 65%, respectively (SLTR group, 85% and 72.6%, respectively); 30.6% patients received mTORi monotherapy, and 38.7% patients had an early switch to mTORi in the first 3 months after oncologic diagnosis. mTORi monotherapy or oncologic treatment strategies had a nonsignificant association with prognosis. The OS rate was higher when the mTORi switch occurred early, 83% and 67%, respectively.

Conclusions: mTORi-based immunosuppression may be a preferred option in patients transplanted with tumors. The OS rate was comparable to data from the SLTR. An mTORi early switch improves OS rate.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Antineoplastic Agents / therapeutic use*
  • Bile Duct Neoplasms / drug therapy*
  • Bile Duct Neoplasms / etiology
  • Bile Duct Neoplasms / mortality
  • Calcineurin Inhibitors / therapeutic use*
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / mortality
  • Cholangiocarcinoma / drug therapy
  • Cholangiocarcinoma / etiology
  • Cholangiocarcinoma / mortality
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / etiology
  • Liver Neoplasms / mortality
  • Liver Transplantation / adverse effects
  • Male
  • Middle Aged
  • Postoperative Complications / drug therapy*
  • Postoperative Complications / etiology
  • Postoperative Complications / mortality
  • Prognosis
  • Retrospective Studies
  • TOR Serine-Threonine Kinases / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • MTOR protein, human
  • TOR Serine-Threonine Kinases