Safety of mTOR inhibitors in adult solid organ transplantation

ABSTRACT

Introduction: Mammalian target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) are a class of immunosuppressive drugs approved for solid organ transplantation (SOT). By inhibiting the ubiquitous mTOR pathway, they present a peculiar safety profile. The increased incidence of serious adverse events in early studies halted the enthusiasm as a kidney sparing alternative to calcineurin inhibitors (CNI).

Areas covered: Herein we review mTOR inhibitors safety profile for adult organ transplantation, ranging from acute side effects, such as lymphoceles, delayed wound healing, or cytopenias, to long-term ones which increase morbidity and mortality, such as cancer risk and metabolic profile. Infection, proteinuria, and cutaneous safety profiles are also addressed.

Expert opinion: In the authors’ opinion, mTOR inhibitors are a safe alternative to standard immunosuppression therapy with CNI and mycophenolate/azathioprine. Mild adverse events can be easily managed with an increased awareness and close monitoring of trough levels. Most serious side effects are dose- and organ-dependent. In kidney and heart transplantation mTOR inhibitors may be safely used as either low-dose de novo or through early-conversion. In the liver, conversion 4 weeks post-transplantation may reduce long-term chronic kidney disease secondary to calcineurin nephrotoxicity, without increasing hepatic artery/portal vein thrombosis.

KEYWORDS:

• Everolimus
• mTOR inhibitor
• NODAT
• rapamycin
• sirolimus
• solid organ transplant

Article highlights

• mTOR inhibitors present a peculiar safety profile.

• Most side effects are dose dependent.

• Edema, wound healing, and cytopenias are the most frequent immediate side effects.

• mTOR inhibitors reduce incidence of CMV and BKV infection, as reduce incidence of EBV-associated PTLD.

• mTOR inhibitors, when managed by an experienced team, are a viable and in some cases better alternative to standard immunosuppression.

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Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.