Articles

Immune checkpoint inhibitor and kidney transplantation

BJMO - 2019, issue 2, february 2019

Maxime Winant

A 50 years old kidney transplant recipient was diagnosed with spinal cell carcinoma.

He started hemodialysis (1981) for FSGS and he underwent a 3rd renal transplantation in 2013, the other two grafts being lost for chronic rejection. Immunosuppression was progressively diminished for relapsing spinal cell carcinomas since 2013. mTOR-inhibitors were not tolerated by the patient.

In March 2018, the patient developed a lesion suspected of spinal cell carcinoma in the right pre-auricular region that infiltrated the parotid gland and the temporomandibular joint. The 26.04.2018 a right parotidectomy, lymphoadenectomy and resection of external auditory canal were performed. Histology showed pT3N0 epidermoid cell carcinoma. Radiotherapy was started without any beneficial effect on the tumor with PET-CT and MRI showing several osteolytic lesions and meningeal involvement. First line chemotherapy with Cisplatine and 5FU was given with no effect. Anti -PD1 treatment was, then, given as rescue therapy.

This challenging case reflects the difficulties we faced in order to decide the treatment options: if chemotherapy is administered nephrotoxic drugs (such as cisplatine) are mandatory while novel treatment modalities such as immunotherapy may jeopardize the graft viability since immunosuppression is modulated by liberating the PD1-pathway.

The use of immune checkpoint inhibitor in patients with solid organ allografts is relatively unknown but mechanism of action suggests an increased risk of rejection; the literature is poor and contain only a limited number of reported cases.

The recommendations in using checkpoint inhibitors in cancer treatment support immunosuppression minimization in order to enhance the action of these drugs. This, ad to use of cytotoxic T lymphocyte stimulation, is associated in the majority of cases to cell-mediated/humoral rejection. (1)(2)

Our patient is included in a study to benefit from an off label PD-1 inhibitor Cemiplimab. The adverse events of this molecule are similar to other PD-1 inhibitor. (3) We supposed that the risk of rejection is high, but that the neoplastic disease needed an innovative treatment since previous treatments failed.

This case illustrates the complexity to choose a treatment that may improve the survival of a cancer transplanted patient but involve high probability of major events such as transplant rejection.

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