Long-Term Efficacy and Allograft Loss after Immune Checkpoint Inhibitor Therapy in Solid Organ Transplant Recipients with Advanced Cutaneous Squamous Cell Carcinoma

Background: Immune checkpoint inhibitors (ICIs) can provide effective treatment for advanced cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients (SOTRs), but long-term oncologic and allograft outcomes remain poorly characterized. Objective: To evaluate long-term efficacy and allograft outcomes after ICI therapy in SOTRs with advanced CSCC. Methods: We conducted a retrospective cohort study of SOTRs with advanced CSCC treated with systemic ICI at Mass General Brigham from 2016-2025. Tumor response, survival, immune-related adverse events, immunosuppression modifications, rejection rate, and graft loss were assessed. Kidney graft failure was analyzed using competing-risk methods with death as a competing event. Results: Among 36 SOTRs, objective response rate was 44.4% (95% CI, 27.9%-61.9%), including 9 complete responses. At 3 years, progression-free, disease-specific, and overall survival were 18.6%, 65.8%, and 32.5%, respectively. Median follow-up was 42.1 months. Five patients experienced graft loss, all kidney recipients; 4 had biopsy-confirmed rejection. The 3-year cumulative incidence of kidney graft failure was 16.7% (95% CI, 2.9%-30.5%). Limitations: Retrospective design, modest sample size, and heterogeneous immunosuppression limited risk-factor analyses. Conclusion: ICI provided long-term CSCC control with a low rate of allograft loss, highlighting the need for longitudinal multidisciplinary management balancing oncologic benefit, graft preservation, and competing mortality risk.