A 58-year-old renal transplant recipient on tacrolimus develops metastatic melanoma. The oncology team considers pembrolizumab. Why is pembrolizumab contraindicated in solid organ transplant recipients?

• A PD-1 blockade impairs tacrolimus metabolism via CYP3A4 induction, causing toxicity
• B Anti-PD-1 antibodies cross-react with donor HLA antigens, triggering hyperacute rejection
• C Pembrolizumab directly damages renal tubular cells, compounding calcineurin inhibitor nephrotoxicity
• D PD-1/PD-L1 signaling is required for allograft tolerance; blockade risks acute graft rejection ✓

Explanation

PD-1/PD-L1 signaling maintains peripheral tolerance including allograft tolerance. Checkpoint inhibitor blockade reactivates T cells against donor antigens, causing acute rejection in up to 40-50% of solid organ transplant recipients. This is a well-documented contraindication. CYP3A4 induction and direct nephrotoxicity are not relevant mechanisms.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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