COMMENTARY

Transplantation and Risk for Malignant Melanoma

Graeme M. Lipper, MD

Disclosures

January 05, 2018

Transplantation and Malignant Melanoma

Solid organ transplantation, although lifesaving for patients with end-stage renal, liver, or heart disease, requires chronic immunosuppressive therapy that increases the risk for cancer, including lymphoma and skin cancer.[1] In this context, skin cancers arising in organ transplant recipients are more frequent, more aggressive,[2] and more likely to be malignant melanomas.[3]

Renal transplant recipients are up to 5 times more likely to develop malignant melanoma compared with the general population,[4] and those with melanoma are more likely to die of their disease.[5] Hence, early detection is of paramount importance in this high-risk population. But are some renal transplant recipients more likely than others to develop malignant melanoma?

To address this important question, Ascha and colleagues[6] conducted a large cohort study of 105,174 renal transplant recipients between 2004 and 2012 (United States Renal Data System; 60.7% men; mean age, 49.6 years). Their aim was to identify the incidence of malignant melanoma and risk factors in this vulnerable population.

Study Findings

The key study findings included the following:

  • In this cohort, renal transplant recipients were 4.9 times more likely than the general US population to develop malignant melanoma (Surveillance, Epidemiology, and End Results data from the National Cancer Institute, 2005-2012);

  • The strongest risk factors for malignant melanoma among renal transplant recipients were older age, male sex, white race, living donors, and fewer than four HLA mismatches;

  • Male sex and older age correlated with poorer survival in renal transplant recipients with malignant melanoma;

  • Both sirolimus and cyclosporine were associated with reduced survival in renal transplant recipients with malignant melanoma (hazard ratio [HR] per year for sirolimus, 1.54; HR for cyclosporine, 1.93); and

  • Transplant recipients who developed malignant melanoma did so within a median of 1.45 years.

Viewpoint

This large retrospective cohort analysis confirms that renal transplant recipients have a fivefold increased risk of developing malignant melanoma. In addition, melanomas appear to be more lethal in elderly and male transplant recipients, and those who continue immunosuppressive therapy with cyclosporine or sirolimus. In this context, renal transplant recipients should be monitored closely for suspicious or changing pigmented lesions, and routine total body skin exams (annual or biannual, depending on history and other risk factors) should be the standard of care.

Chronic immunosuppression increases the risk for cancer through multiple pathways, including impaired immune surveillance of tumor cells and reduced clearance of oncogenic viruses, such as human papillomavirus. Future studies should aim to characterize the relationship between different immunosuppressive regimens (combinations, doses), melanoma risk, incidence of metastatic disease, and survival.

These study findings also raise a therapeutic challenge, because renal transplant recipients with melanoma need to be treated. Should they be managed more aggressively, with a lower threshold for sentinel lymph node biopsy and full staging? And how should metastatic disease be managed? Can immune checkpoint inhibitors, such as ipilimumab, be used safely in this high-risk population,[7] and is there a way to encourage the host's immune response to melanoma cells without risking organ failure? As more renal transplant recipients develop cancer—including malignant melanoma—over time, these practical questions will need to be addressed.

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