Effect of mechanistic target of rapamycin inhibitors on postrenal transplantation malignancy: A nationwide cohort study

Cancer Med. 2018 Sep;7(9):4296-4307. doi: 10.1002/cam4.1676. Epub 2018 Aug 16.

Abstract

Background: Post-transplantation malignancy influenced graft survival and overall survival in the patients receiving renal transplantation. Immunosuppressants influenced the immune surveillance, but whether immunosuppressive agents have impact for incidence of post-transplantation malignancy is still elusive in Taiwan.

Method: We conducted a nationwide population-based study. Patients who did not have malignancy history and received kidney transplantation between 2000 and 2010 were enrolled. Specific immunosuppressive users are defined as sustained use (more than 12 months) after renal transplantation. The primary outcome is the development of cancer after kidney transplantation. A Cox proportional hazards model was used to determine the risk of cancer development.

Result: Among 4438 recipients, 559 of them were diagnosed with malignancy after 1 year of transplantation. A total of 742 of recipients were as user of mechanistic target of rapamycin (mTOR) inhibitors. The mTOR users had higher rate of receiving pulse therapy. The hazard ratios (HR) for mTOR inhibitor users with exposure more than 5 years for overall malignancy and urothelial malignancy were 0.68 (95% CI: 0.48-0.95, P = 0.02) and 0.60 (95% CI: 0.36-0.99, P = 0.02), respectively. For the overall mortality and reentry of dialysis, the probability of both groups was similar (overall mortality: P = 0.53; reentry of dialysis: P = 0.77).

Conclusion: Among the recipients of renal transplantation in Taiwan, mTOR inhibitors with exposure more than 5 years provided a protective role in reducing the risk of overall neoplasm and urothelial malignancy. The probability of reentry of dialysis and overall mortality was similar between the mTORi users and nonusers.

Keywords: malignancy; mechanistic target of rapamycin inhibitor; renal transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Comorbidity
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Incidence
  • Kaplan-Meier Estimate
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Neoplasms / epidemiology*
  • Neoplasms / etiology*
  • Prognosis
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Risk Assessment
  • Risk Factors
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Protein Kinase Inhibitors
  • TOR Serine-Threonine Kinases