TY - JOUR
T1 - Immune checkpoint inhibitors in solid organ transplant recipients with advanced skin cancers-emerging strategies for clinical management
AU - Ferrándiz-Pulido, Carla
AU - Leiter, Ulrike
AU - Harwood, Catherine
AU - Proby, Charlotte M.
AU - Guthoff, Martina
AU - Scheel, Christina H.
AU - Westhoff, Timm H.
AU - Bouwes Bavinck, Jan Nico
AU - Meyer, Thomas
AU - Nägeli, Mirjam C.
AU - Del Marmol, Veronique
AU - Lebbé, Celeste
AU - Geusau, Alexandra
N1 - Copyright:
© 2023 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2023/7
Y1 - 2023/7
N2 - 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.
AB - 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.
KW - transplantation
KW - solid organ transplant recipients
KW - immune checkpoint inhibitors
KW - rejection
KW - skin cancer
KW - melanoma
KW - merkel cell carcinoma
KW - squamous cell carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85149790985&partnerID=8YFLogxK
U2 - 10.1097/TP.0000000000004459
DO - 10.1097/TP.0000000000004459
M3 - Review article
C2 - 36706163
SN - 0041-1337
VL - 107
SP - 1452
EP - 1462
JO - Transplantation
JF - Transplantation
IS - 7
ER -