Risk of Melanoma in Kidney Transplant Recipients Associated with Older Age, Sex, and Donor Type

Patients who undergo kidney transplantation for long-term curative treatment of end-stage renal disease are required to maintain lifelong immunosuppressive treatment to ensure adequate graft function. The immunosuppression therapy is associated with an increase in the risk of certain kinds of cancers, particularly cancer of the skin, leading to increased morbidity and mortality in transplant recipients.

The risk of skin cancer, such as melanoma, is increased according to the type, intensity, and duration of immunosuppressive therapy following transplantation. Two mechanisms are associated with the increased risk of melanoma: (1) immunosuppressive agents are inherently carcinogenic, and (2) the body’s self-defense against malignant changes is inhibited with chronic immunosuppression. Compared with the general population, the risk of melanoma in solid-organ transplant recipients is increased 3- to 5-fold.

In the past decade, there have been changes in immunosuppression regimens and novel immunosuppressive agents have been developed. Mona Ascha, MD, and colleagues in Cleveland, Ohio, conducted a retrospective cohort study designed to provide an up-to-date review of the incidence of melanoma in kidney transplant recipients. The researchers utilized a cohort from the United States Renal Data System (USRDS) from the years 2004 through 2012 to assess the risk factors associated with the development of melanoma in that patient population. They reported study results in JAMA Dermatology [doi:10.1001/jamadermatol.2017.2291].

The USRDS combines data from the United Network for Organ Sharing with Medicare and Medicaid payment data. The researchers identified 105,174 people who were first-time kidney transplantation recipients between 2004 and 2012 and had a record of a Medicare claim. Of those, 0.46% (n=488) had an International Classification of Diseases, Ninth Revision, Clinical Modification code for melanoma.
Compared with those who did not develop melanoma, those who did receive a melanoma diagnosis were older (49.7 vs 60.4 years; P<.001), and more likely to be male (60.7% vs 71.5%, P<.001). When stratified according to four or more human leukocyte antigen (HLA) mismatches compared with fewer than four HLA mismatches, the proportion of those with four or more HLA mismatches was greater among patients without melanoma than among those with a diagnosis of melanoma (62.9% vs 55.1%; P<.001). Mean donor age was greater for those with melanoma than for those in the nonmelanoma group (42.6 vs 39.2 years; P<.001)

Nearly all of the patients with melanoma were white (96.1%); proportions of Native Americans, Asians, blacks, and Hispanics were 0.6%, 1.0%, 2.3%, and 5.5%, respectively. In the nonmelanoma group, 66.5% were white, with the other racial groups being 1.0%, 5.0%, 27.5%, and 14.2%, respectively.

There was a significant difference in the proportion of white kidney donors in the melanoma group compared with the nonmelanoma group (92.4% vs 82.9%, P<.001). The proportion of living donors was also higher in the group that developed melanoma compared with the nonmelanoma group (44.7% vs 33.7%, P<.001). Finally, those in the melanoma group were significantly more likely to be taking cyclosporine (4.9% vs 3.2%; P=.04) or sirolimus (22.3% vs 13.2%; P<.001) compared with those in the nonmelanoma group.

The overall crude prevalence of melanoma in the USRDS cohort was 0.47%; the prevalence in the USRDS and the Surveillance, Epidemiology, and End Results (SEER) database were standardized to the 2000 US standard population. The overall relative rate of melanoma for USRDS patients compared with SEER patients is 4.9, indicating that USRDS patients were 4.0 times more likely to develop melanoma compared with SEER counterparts. When adjusted for age, the prevalence of melanoma in the kidney transplant population is 208 per 100,000 patients, while the crude prevalence is 462 per 100,000 patients.

In a multivariable Cox proportional hazards model of disease-free survival, age, race, sex, donor type, cyclosporine therapy, and sirolimus therapy had statistically different hazard ratios. There was an association between 1.06 times the hazard with each extra year of age (95% confidence interval [CI], 1.05-1.06; P<.001). In race/ethnicity models, Asian, African American, and Hispanic transplant recipients had decreased hazard ratios of 0.16 (95% CI, 0.06-0.38; P<.001), 0.06 (95% CI, 0.03-0.11; P<.001), and 0.30 (95% CI, 0.20-0.45, P<.001), respectively, compared with white recipients.

Transplant recipients with living donors had 1.35 times the hazard of those with deceased donors (95% CI, 1.11-1.64; P=.002), and long-term immunosuppression with cyclosporine and sirolimus had hazard ratios of 1.93 (95% CI, 1.24-2.99; P=.004) and 1.54 (95% CI, 1.22-1.94; P<.001), respectively.

The study did have some limitations, according to the researchers, including defining participants with melanoma from diagnosis codes, which may have led to under reporting the incidence of melanoma; using SEER as a reference group; and the inability to assess certain melanoma risk factors that were not captured in the USRDS database.

In conclusion, the researchers said, “Renal transplant recipients are at greater risk of developing melanoma than the general population. We provide detained information and identified several important trends and risk factors in this vulnerable patient group that we believe can guide clinicians in providing adequate care.”

Takeaway Points

  • Researchers conducted a retrospective cohort study to assess the risk of renal transplant recipients for developing melanoma and to identify the factors associated with that risk.
  • Using data from the United States Renal Data System for the years 2004 through 2012, the researchers identified 105,174 first-time kidney transplantation recipients who had a Medicare claim; of those, 0.46% (n=488) had a ICD-9-CM diagnosis code for melanoma.
  • The risk factors for development of melanoma identified in the study included older age among recipients and donors, white race, living donors, and long-term therapy with sirolimus and cyclosporine.