Non‐melanoma skin cancer is reduced after switch of immunosuppression to mTOR‐inhibitors in organ transplant recipients

Alter, Mareike; Satzger, Imke; Schrem, Harald; Kaltenborn, Alexander; Kapp, Alexander; Gutzmer, Ralf

doi:10.1111/ddg.12355

Cited by 30 publications

(23 citation statements)

References 39 publications

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“…No new skin lesions developed after everolimus replaced CNI therapy, over a minimum follow-up of six months. Low rates of recurrence were also reported over a 24-month follow-up period in five transplant recipients (including two kidney transplant patients) by Alter and colleagues after switch from CNI to everolimus [67]. Limited data from heart transplantation also points to a protective effect for everolimus in patients with skin cancers [68] (see “Heart Transplantation”).…”

Section: Kidney Transplantationmentioning

confidence: 92%

Everolimus and Malignancy after Solid Organ Transplantation: A Clinical Update

Holdaas

Simone

Zuckermann

2016

Journal of Transplantation

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Malignancy after solid organ transplantation remains a major cause of posttransplant mortality. The mammalian target of rapamycin (mTOR) inhibitor class of immunosuppressants exerts various antioncogenic effects, and the mTOR inhibitor everolimus is licensed for the treatment of several solid cancers. In kidney transplantation, evidence from registry studies indicates a lower rate of de novo malignancy under mTOR inhibition, with some potentially supportive data from randomized trials of everolimus. Case reports and small single-center series have suggested that switch to everolimus may be beneficial following diagnosis of posttransplant malignancy, particularly for Kaposi's sarcoma and nonmelanoma skin cancer, but prospective studies are lacking. A systematic review has shown mTOR inhibition to be associated with a significantly lower rate of hepatocellular carcinoma (HCC) recurrence versus standard calcineurin inhibitor therapy. One meta-analysis has concluded that patients with nontransplant HCC experience a low but significant survival benefit under everolimus monotherapy, so far unconfirmed in a transplant population. Data are limited in heart transplantation, although observational data and case reports have indicated that introduction of everolimus is helpful in reducing the recurrence of skin cancers. Overall, it can be concluded that, in certain settings, everolimus appears a promising option to lessen the toll of posttransplant malignancy.

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Section: Kidney Transplantationmentioning

confidence: 92%

Everolimus and Malignancy after Solid Organ Transplantation: A Clinical Update

Holdaas

Simone

Zuckermann

2016

Journal of Transplantation

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“…For example, switching patients to sirolimus has been demonstrated to reduce risk of posttransplant skin cancer 44. patient on a specific treatment regime.…”

mentioning

confidence: 99%

“…patient on a specific treatment regime. For example, switching patients to sirolimus has been demonstrated to reduce risk of posttransplant skin cancer 44. The knowledge of a patient's polygenic risk of skin cancer posttransplant could also inform less drastic interventions such as frequency of checks with dermatologists and may also increase a patient's likelihood to take on board lifestyle interventions such as wearing sunscreen and carrying out regular skin checks.…”

mentioning

confidence: 99%

Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort

Stapleton

Birdwell

McKnight

et al. 2019

American Journal of Transplantation

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Renal transplant recipients have an increased risk of non-melanoma skin cancer (NMSC) compared to in the general population. Here, we show polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of NMSC in a general, nontransplant setting, can predict risk of, and time to posttransplant skin cancer. Genetic variants, reaching predefined P-value thresholds were chosen from published squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) nontransplant GWAS. Using these GWAS, BCC and SCC PRS were calculated for each sample across three European ancestry renal transplant cohorts (n = 889) and tested as predictors of case:control status and time to NMSC posttransplant. BCC PRS calculated at P-value threshold 1 × 10 was the most significant predictor of case:control status of NMSC posttransplant (OR = 1.61; adjusted P = .0022; AUC [full model adjusted for clinical predictors and PRS] = 0.81). SCC PRS at P-value threshold 1 × 10 was the most significant predictor of time to posttransplant NMSC (adjusted P = 9.39 × 10 ; HR = 1.41, concordance [full model] = 0.74). PRS of nontransplant NMSC is predictive of case:control status and time to NMSC posttransplant. These results are relevant to how genomics can risk stratify patients to help develop personalized treatment regimens.

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“…When immunosuppressed patients were switched from calcineurin inhibitors to mTOR inhibitors, Alberú et al 38 found that skin cancer rates were three times lower in the mTOR inhibitor group after two years. Alter et al 39 reported a significant decrease of SCC development in SOTRs as early as the first year after changing immunosuppression to mTOR-inhibitors. Furthermore, Gu et al 40 reported that sirolimus has an anti-tumor effect and sirolimus-based immunosuppression decreases rates of both SCC and BCC in kidney transplant recipients.…”

Section: Discussionmentioning

confidence: 99%

Clinical Findings, Treatments and Outcomes of Transplant Recipients with Metastatic Skin Cancer

2017

ARC Journal of Dermatology

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Non‐melanoma skin cancer is reduced after switch of immunosuppression to mTOR‐inhibitors in organ transplant recipients

Abstract: Switch of the immunosuppressive regimen to mTOR-inhibitors should be considered for organ transplant recipients suffering from multiple non-melanoma skin cancers.

Cited by 30 publications

References 39 publications

Everolimus and Malignancy after Solid Organ Transplantation: A Clinical Update

Everolimus and Malignancy after Solid Organ Transplantation: A Clinical Update

Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort

Clinical Findings, Treatments and Outcomes of Transplant Recipients with Metastatic Skin Cancer

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