Calcineurin-inhibitor free immunosuppression after lung transplantation - a single center case-control study in 51 patients converted to Mechanistic Target of Rapamycin (mTOR) inhibitors

PLoS One. 2023 May 18;18(5):e0284653. doi: 10.1371/journal.pone.0284653. eCollection 2023.

Abstract

Background: Data on calcineurin-inhibitor (CNI) free immunosuppression after lung transplantation (LTx) are limited. Aim of this study was to investigate CNI-free immunosuppression using mechanistic target of rapamycin (mTOR) inhibitors.

Methods: This retrospective analysis was performed at a single center. Adult patients after LTx without CNI during the follow-up period were included. Outcome was compared to those LTx patients with malignancy who continued CNI.

Results: Among 2,099 patients in follow-up, fifty-one (2.4%) were converted median 6.2 years after LTx to a CNI-free regimen combining mTOR inhibitors with prednisolone and an antimetabolite, two patients were switched to mTOR inhibitors with prednisolone only. In 25 patients, malignancies without curative treatment options were the reason of the conversion, with a 1-year survival of 36%. The remaining patients had a 1-year survival of 100%. Most common non-malignant indication was neurological complications (n = 9). Fifteen patients were re-converted to a CNI-based regimen. The median duration of CNI-free immunosuppression was 338 days. No acute rejections were detected in 7 patients with follow-up biopsies. In multivariate analysis, CNI-free immunosuppression were not associated with improved survival after malignancy. The majority of patients with neurological diseases improved 12 months after conversion. Glomerular filtration rate increased by median 5 (25 and 75% percentiles -6; +18) ml/min/1.73 m2.

Conclusions: mTOR inhibitor based CNI-free immunosuppression may be safely performed in selected patients after LTx. This approach was not associated with improved survival in patients with malignancy. Significant functional improvements were observed in patients with neurological diseases.

MeSH terms

  • Adult
  • Calcineurin Inhibitors / therapeutic use
  • Calcineurin*
  • Case-Control Studies
  • Glomerular Filtration Rate
  • Graft Rejection / prevention & control
  • Humans
  • Immunosuppression Therapy
  • Immunosuppressive Agents / therapeutic use
  • Lung Transplantation*
  • MTOR Inhibitors
  • Prednisolone
  • Retrospective Studies
  • Sirolimus / therapeutic use
  • TOR Serine-Threonine Kinases

Substances

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

Grants and funding

The author(s) received no specific funding for this work.