Rapid Acute Rejection with Cortical Necrosis after First-Dose Cemiplimab in a Living Donor Kidney Transplant

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Introduction: Transplant recipients (TR) have an increased risk of squamous cell carcinoma (SCC) 65-250 times that of general population. There are few treatment options for advanced SCC in the setting of immunosuppression (IS) which has carcinogenic effect. Cemiplimab (CMP) is a checkpoint inhibitor (CPI) directed at PD-1 which has had promising responses in advanced SCC, but its use has also been associated with acute rejection. However, a recent prospective study using CPM showed safe use in TR with sirolimus (SRL). Case Description: A 71-year-old male, CKD/V due to IgA nephropathy received a living donor TR. He has a history of BCC treated with Moh's surgery 5 months (Ms) pretransplant. He received basiliximab induction and maintained on a standard IS of tacrolimus (TAC), mycophenolate (MMF), and prednisone. Creatinine (Cr) settled at 1.4 mg/dL. 5 Ms post-transplant (PTx), 15 spots of actinic keratoses were treated with cryotherapy. A month later, he had neutropenia, so MMF was changed to everolimus. By 8 Ms PTx, he had CMV disease so everolimus was held kept him on prednisone and TAC. He had 2 biopsies at 2 and 9 Ms PTx which showed no rejection. A year PTx, he developed DSA treated with IVIG. Then, he was diagnosed with multiple BCC and SCC involving his face, ear, and hands. He had multiple facial surgeries to control his SCC but the lesions progressed. 19 Ms PTx, CMP was given as salvage therapy for advanced SCC. TAC was switched to SRL while Cr was 1.3 mg/dL. 1 week after the first dose of CMP, he experienced fever and malaise with rise in Cr to 3 mg/dl. He was admitted with oliguria and Cr of 4.7 mg/dL and treated with IV steroid then biopsy showed acute cortical necrosis and vascular inflammation. The patient started on dialysis. Discussion: Until recently, TR were excluded from CPI's treatment for the risk of organ rejection. A recent prospective study reported favorable outcomes for 12 subjects who used CMP for the treatment for advanced SCC along with SRL with no rejection at 6 months. Our patient suffered from a rapid aggressive acute rejection at 1 week after first dose of CMP that resulted in cortical necrosis and graft loss. This is the first case of rapid renal allograft loss due to acute rejection and cortical necrosis after the CMP reported in literature.

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