Immune checkpoint inhibitors in solid organ transplant recipients with advanced skin cancers-emerging strategies for clinical management

Carla Ferrándiz-Pulido, Ulrike Leiter, Catherine Harwood, Charlotte M. Proby, Martina Guthoff, Christina H. Scheel, Timm H. Westhoff, Jan Nico Bouwes Bavinck, Thomas Meyer, Mirjam C. Nägeli, Veronique Del Marmol, Celeste Lebbé, Alexandra Geusau (Lead / Corresponding author)

Research output: Contribution to journalReview articlepeer-review

7 Citations (Scopus)
34 Downloads (Pure)

Abstract

Use of immune checkpoint inhibitors (ICIs) in solid organ transplant recipients (SOTRs) with advanced skin cancers presents a significant clinical management dilemma. SOTRs and other immunosuppressed patients have been routinely excluded from ICI clinical trials with good reason: immune checkpoints play an important role in self- and allograft-tolerance and risk of acute allograft rejection reported in retrospective studies affects 10% to 65% of cases. These reports also confirm that cutaneous squamous cell carcinoma and melanoma respond to ICI therapy, although response rates are generally lower than those observed in immunocompetent populations. Prospective trials are now of critical importance in further establishing ICI efficacy and safety. However, based on current knowledge, we recommend that ICIs should be offered to kidney transplant recipients with advanced cutaneous squamous cell carcinoma, melanoma, or Merkel cell carcinoma if surgery and/or radiotherapy have failed. For kidney transplant recipients, this should be first line ahead of chemotherapy and targeted therapies. In SOTRs, the use of ICIs should be carefully considered with the benefits of ICIs versus risks of allograft rejection weighed up on a case-by-case basis as part of shared decision-making with patients. In all cases, parallel management of immunosuppression may be key to ICI responsiveness. We recommend maintaining immunosuppression before ICI initiation with a dual immunosuppressive regimen combining mammalian target of rapamycin inhibitors and either corticosteroids or calcineurin inhibitors. Such modification of immunosuppression must be considered in the context of allograft risk (both rejection and also its subsequent treatment) and risk of tumor progression. Ultimately, a multidisciplinary approach should underpin all clinical decision-making in this challenging scenario.

Original languageEnglish
Pages (from-to)1452-1462
Number of pages11
JournalTransplantation
Volume107
Issue number7
Early online date5 Jan 2023
DOIs
Publication statusPublished - Jul 2023

Keywords

  • transplantation
  • solid organ transplant recipients
  • immune checkpoint inhibitors
  • rejection
  • skin cancer
  • melanoma
  • merkel cell carcinoma
  • squamous cell carcinoma

ASJC Scopus subject areas

  • Transplantation

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