Cemiplimab for kidney transplant recipients with advanced skin squamous cell carcinoma

Solid organ transplant recipients carry the highest risk of cutaneous squamous cell carcinoma of any group, and the drug that works for advanced disease is the one they are excluded from receiving, because PD-1 blockade can trigger rejection of the graft. That exclusion is not a footnote: it means the group with the worst disease has no evidence at all.

This phase 1 study at Dana-Farber built a protocol around the problem. Immunosuppression was cross-tapered to a mammalian target of rapamycin inhibitor, and prednisone was pulsed around each cycle at 40 mg daily from the day before through day 3, 20 mg on days 4 to 6 and 10 mg until the day before the next cycle. Cemiplimab 350 mg was then given every three weeks for up to two years.

Twelve patients were treated. No kidney rejection and no graft loss occurred, which was the primary endpoint. A response was seen in five of eleven evaluable patients (46 per cent, 90 per cent confidence interval 22 to 73), two of them lasting beyond a year. Median follow-up was 6.8 months, with a range of 0.7 to 29.8.

The risks were not only immunological. Treatment-related grade 3 or higher adverse events occurred in five patients (42 per cent), including diarrhoea, infection and metabolic disturbance, and one patient died of angioedema and anaphylaxis attributed to the mammalian target of rapamycin inhibitor cross-taper, not to the cemiplimab. Twelve patients is twelve patients. But it is the first prospective evidence that the combination can be given, and the regimen it describes is what a transplant nephrologist and an oncologist can now discuss instead of refusing treatment outright.