Pembrolizumab-induced severe rejection and graft intolerance syndrome resulting in renal allograft nephrectomy

Introduction

Pembrolizumab is a selective anti-programmed cell death protein-1 (PD-1) humanized monoclonal antibody that inhibits PD-1 activity by binding to the PD-1 receptor that is found on activated T-cells. The goal of the treatment is to allow the immune system to target and destroy cancer cells by preventing cancer cells from binding to PD-1 receptors, leading to decreased tumor growth. The activation of T-cells by pembrolizumab not only leads to the destruction of malignant cells but also attacks the donor alloantigens that are present in a renal transplant, resulting in graft rejection.

Case report

We present a case of a 46-year-old African American female with history of renal transplant who was treated with pembrolizumab for stage IV B endometrial adenocarcinoma and experienced renal transplant rejection and severe graft intolerance syndrome.

Management and outcome: Due to ongoing graft intolerance, a transplant nephrectomy was performed. Allograft pathology was consistent with non-viable kidney with tubulitis, interstitial fibrosis and necrosis consistent with transplant rejection without any evidence of malignancy.

Discussion

As emphasized in our case, there is a very high risk of graft rejection in patients who need to be placed on immunomodulators such as pembrolizumab, so the risk versus benefit needs to be assessed and discussed. Our case is unique because pembrolizumab not only caused graft rejection but also severe graft intolerance syndrome which led to transplant nephrectomy. Further guidelines are needed in renal transplant patients requiring PD-1 inhibitors to establish the ideal treatment plan of immunosuppression management and anti-cancer treatments.