Graft and infectious outcomes following immune checkpoint inhibitor exposure in kidney transplant recipients with non-melanoma skin cancer: A multicenter real-world study.

Abstract

e21563 Background: Kidney transplant recipients (KTRs) face a disproportionately high risk of non-melanoma skin cancer (NMSC) due to chronic immunosuppression. While immune checkpoint inhibitors (ICIs) have revolutionized NMSC management, their use in KTRs remains controversial due to high rates of allograft rejection (40%–50%) reported in small, retrospective series. Real-world evidence characterizing both graft and infectious outcomes in KTRs with NMSC remains limited. We utilized a large multicenter database to evaluate outcomes in KTRs receiving ICI therapy. Methods: This retrospective cohort study used de-identified EHR data from the TriNetX Research Network. Adult KTRs with NMSC (2018-2025) were identified and stratified by ICI exposure. Patients treated with any ICI (PD-1/PD-L1/CTLA-4) were compared with ICI-naïve controls. Propensity score matching was performed for demographics, baseline kidney function, immunosuppression regimen, comorbidities, and cancer severity proxies. Outcomes assessed over 730 days of follow-up included graft rejection/failure, dialysis utilization, transplant complications, acute care utilization, and a composite opportunistic/viral infection endpoint. Time-to-event analyses were performed using Kaplan-Meier methods and Cox proportional hazards models. Results: After matching, each cohort included 113 patients. ICI exposure was associated with significantly higher risk of graft rejection or failure (19.5% vs 9.7%; HR 2.43, 95% CI 1.17-5.02, p = 0.01) and opportunistic/viral infections (21.2% vs 13.3%; HR 2.08, 95% CI 1.09-3.99, p = 0.02). ICI therapy was also associated with increased transplant-related complications (35.4% vs 30.1%; HR 1.59, 95% CI 1.00-2.53, p = 0.05) and acute care utilization (61.1% vs 48.7%; HR 1.72, 95% CI 1.20-2.47, p < 0.01). Dialysis utilization was numerically higher in the ICI cohort (19.5% vs 14.2%; HR 1.59, 95% CI 0.83-3.03) but did not reach statistical significance (p = 0.16). Table 1. Conclusions: In this propensity-matched real-world cohort of KTRs with NMSC, ICI therapy was associated with approximately two-fold higher rates of graft rejection/failure and infections over 2 years. These findings represent clinically important safety signals and support multidisciplinary risk-benefit assessment and close graft monitoring when ICIs are considered in kidney transplant recipients. Key outcomes over 2-years after immune checkpoint inhibitor exposure. Outcome ICI (n=113) No ICI (n=113) HR (95% CI) P value Graft rejection/failure 19.5% 9.7% 2.43 (1.17-5.02) 0.01 Opportunistic/viral infections 21.2% 13.3% 2.08 (1.09-3.99) 0.02 Transplant complications 35.4% 30.1% 1.59 (1.00-2.53) 0.05 Acute care utilization 61.1% 48.7% 1.72 (1.20-2.47) <0.01 Dialysis utilization 19.5% 14.2% 1.59 (0.83-3.03) 0.16