Immunotherapy in Liver Transplant Recipients with Advanced Solid Malignancies: A Three-Patient Case Series

The use of immune checkpoint inhibitors (ICIs) after liver transplantation (LT) remains controversial, because immune activation may cause allograft rejection. Evidence in non-hepatocellular carcinoma (HCC) malignancies is limited. We retrospectively reviewed three LT recipients treated with pembrolizumab for advanced non-HCC malignancies at the McGill University Health Centre; treatment began between May 2020 and January 2025, and follow-up was censored on 31 January 2026. A patient with PD-L1-negative non-small cell lung cancer (NSCLC) achieved stable disease for approximately seven months, whereas a patient with PD-L1-high NSCLC achieved a durable partial response with progression-free survival of approximately 36 months. A third patient with cutaneous squamous cell carcinoma achieved a near-complete radiologic and metabolic response after two cycles. Pembrolizumab was held after this response; subsequent liver-test abnormalities raised concern for graft injury, but biopsy showed no histologic rejection and supported treatment resumption. No clinical or biochemical evidence of rejection was observed in Cases 1 and 2. At cutoff, Case 3 was alive and receiving pembrolizumab after seven cycles. These cases support a cancer-specific, individualized risk-benefit assessment in which expected oncologic benefit, alternatives, graft history, immunosuppression, and acceptance of graft-loss risk guide multidisciplinary treatment and close graft surveillance.