Mammalian target of rapamycin inhibitors for prolonged secondary prevention of nonmelanoma skin cancer in solid organ transplant recipients

Dermatol Ther. 2022 Aug;35(8):e15649. doi: 10.1111/dth.15649. Epub 2022 Jun 29.

Abstract

Immunosuppressive agents are essential for graft survival in solid-organ transplant recipients (SOTRs), but they have substantial durable side effects, including a higher incidence of aggressive nonmelanoma skin cancers (NMSCs). Hitherto, only one class of immunosuppressants, mammalian target of rapamycin inhibitors (mTORi), may inhibit skin tumor formation, however their durable effectiveness is controversial. To evaluate the sustained effectiveness of mTORi in reducing NMSCs' incidence in SOTRs, a retrospective study was conducted in a specialized dermatology clinic for SOTRs of a tertiary university-affiliated medical center. SOTRs with a history of at least one histologically proven NMSC were followed for 6 years: 3 years after transplantation, before initiation of mTORi, and 3 years under mTORi treatment. The cohort consisted of 44 SOTRs. Treatment with mTORi was initiated on average 6.27 (3.34-6.34) years following transplantation. In the 3 years before mTORi treatment initiation, the mean number of new NMSCs per patient was 2.11 (1-14). This value decreased to 1.2 (0-19) in the 3 years under mTORi treatment (p = 0.0007). Analysis by NMSC type yielded a significant decrease in both SCCs and BCCs. This study found that mTORi are effective for prolonged secondary prevention of NMSCs in SOTRs.

Keywords: immunosuppression; mammalian target of rapamycin inhibitors; nonmelanoma skin cancers; solid-organ transplant recipients; squamous cell carcinoma.

MeSH terms

  • Carcinoma, Basal Cell* / etiology
  • Carcinoma, Basal Cell* / pathology
  • Carcinoma, Basal Cell* / prevention & control
  • Carcinoma, Squamous Cell* / etiology
  • Carcinoma, Squamous Cell* / pathology
  • Carcinoma, Squamous Cell* / prevention & control
  • Humans
  • Immunosuppressive Agents* / adverse effects
  • MTOR Inhibitors* / therapeutic use
  • Organ Transplantation* / adverse effects
  • Retrospective Studies
  • Secondary Prevention
  • Sirolimus / therapeutic use
  • Skin Neoplasms* / etiology
  • Skin Neoplasms* / pathology
  • Skin Neoplasms* / prevention & control
  • TOR Serine-Threonine Kinases / antagonists & inhibitors

Substances

  • Immunosuppressive Agents
  • MTOR Inhibitors
  • TOR Serine-Threonine Kinases
  • Sirolimus