Pembrolizumab

A 19-year-old woman with metastatic, unresectable adrenocortical carcinoma developed grade 3 immune-related hepatitis following a single dose of pembrolizumab, which was administered as salvage therapy after disease progression on prior treatments. The woman initially presented with severe hypertension, hypokalaemia and clinical features of Cushing syndrome. Imaging identified a large left adrenal mass encasing a major vessel, et al. left renal lesion, et al. right ovarian teratoma and multiple pulmonary micronodules. 18-FDG-PET demonstrated hypermetabolism in the adrenal mass, lung nodules and teratoma. Biochemical evaluation confirmed adrenocorticotropin-independent Cushing syndrome and elevated adrenal androgens. History included prior treatment with mitotane and metyrapone, followed by eight cycles of etoposide-doxorubicin-cisplatin plus mitotane. Despite these therapies, the disease progressed. Adrenal biopsy showed high tumour-infiltrating lymphocytes, low tumour mutation burden, low programmed death-ligand 1 expression and microsatellite stability. Germline testing revealed a TP53 pathogenic variant, consistent with Li-Fraumeni syndrome. She received a single dose of pembrolizumab [route and dosage not stated]. Shortly after, she developed grade 3 immune-related hepatitis, resulting in prolonged hospitalisation and discontinuation of both pembrolizumab and mitotane. The woman required cessation of pembrolizumab and mitotane, and received treatment for hepatitis during her hospital stay. No formal rechallenge was performed. At three months, imaging showed significant regression of the adrenal mass, stable renal and ovarian lesions and resolution of lung nodules. She subsequently underwent complete surgical resection and achieved full remission. At over one year of follow-up, she remains disease free. …