Programmed cell death protein 1 (PD-1) immune checkpoint inhibitors are an effective first line treatment for metastatic melanoma as it has shown to improve overall survival. Organ transplant recipients are at an increase risk of allograft rejection with limited safety and efficacy data as most of these patients were excluded from phase 3 clinical trials.
A 57 years old man received a deceased donor renal allograft for end stage renal disease in 2001. He has been on Tacrolimus and mycophenolate mofetil over the past 13 years with normal renal function. He noticed a rapidly enlarged fungating skin lesion over the right scapula over 3 months. A biopsy confirmed malignant melanoma with no BRAF mutation. Staging CT showed widespread metastases involving the liver and bones. His immunosuppressants were changed to azathioprine and everolimus prior to commencement of pembrolizumab 2mg/kg every 3 weeks.
After two cycles of pembrolizumab, he continued to deteriorate with functional decline and clinically progression of right scapular subcutaneous lesions. Similarly, his renal function worsened rapidly with creatinine > 200 umol/L. Given his poor prognosis and declined haemodialysis, he was transferred to the hospice for best supportive care.
To the best of our knowledge, there has been no case report describing first line PD-1 inhibitor for the management of metastatic melanoma on a renal transplant recipient which subsequent leads to graft rejection and rapid treatment failure. Early evidence has shown a high level of PD-L1 receptor expressed in renal tubules and is responsible for transplant tolerance. Therefore, by blocking with PD-1 inhibitor can accelerate graft failure. Furthermore, there is limited data to help select the appropriate immunosuppressant at the time of initiation of immune checkpoint inhibitor. Recent case reports have document a graft failure following administration of PD-1 inhibitor as compared to successful maintenance of graft with anti-CTLA4 antibody Ipilimumab. Our case highlights the risk of treatment failure and allograft rejection in renal transplant patients treated with anti-PD1 agents. Physician will need to make careful selection of immune checkpoint blockage and discuss risk-benefit with transplant recipients.