Melanoma Risk in 12,205 Kidney Transplant Recipients Receiving Calcineurin Inhibitor-Based Immunosuppression: A Nationwide Analysis of Polish National Health Fund Data (2010–2022)

<b>Background</b>: Numerous studies have demonstrated the impact of post-transplant immunosuppressive therapy on cancer development, particularly in the skin. Despite the growing number of observations, there is still a lack of comprehensive analyses assessing the influence of specific immunosuppressive regimens on the development of melanoma in kidney transplant recipients. The aim of this study was to describe the incidence and temporal patterns of cutaneous melanoma (CM) among kidney transplant recipients in Poland between 2010 and 2022, with particular focus on recipients treated with calcineurin inhibitor (CNI)-based immunosuppression, including cyclosporine (CsA) and tacrolimus (TAC). <b>Methods</b>: This nationwide, descriptive analysis was conducted using comprehensive national administrative data obtained from the Polish National Health Fund (PNHF) and the Polish National Cancer Registry (PNCR). The study assessed the incidence of cutaneous melanoma and temporal trends over the study period. <b>Results</b>: Melanoma skin cancer occurred in 27 cases observed in a population of 12,205 kidney transplant recipients over 13 years of follow-up, corresponding to a final cumulative incidence of 0.23% (95% CI: 0.15-0.34). Calcineurin inhibitor (CNI)-based regimens in kidney transplant recipients were associated with significantly lower risk profiles over 10 years, with only nine cases observed in a cohort of 7107 patients, culminating in a cumulative incidence of 0.13% (95% CI: 0.06-0.24). The stratified analysis of CM incidence under CNI-based immunosuppressive regimens by calcineurin inhibitor type revealed a modest cumulative risk in the TAC subgroup, reaching 0.14% (95% CI: 0.06-0.26) by year 10, with all nine observed cases occurring exclusively in this group, while the CsA subgroup reported zero events throughout the follow-up period. Risk differences progressively increased to 0.14% (95% CI: -0.20 to 0.26) by year 10, but they were not statistically significant in any year (<i>p</i> ≥ 0.230). <b>Conclusions:</b> Although all melanoma cases occurred in the TAC subgroup, the data do not allow us to conclude that TAC confers a higher risk than CsA. This lack of significance likely reflects both the rarity of events and the limited statistical power to detect small differences between TAC and CsA. These results highlight the need for careful dermatologic monitoring in all kidney transplant recipients, while the choice of calcineurin inhibitor should be individualized based on patient-specific factors.