SUN-911 Immunotherapy Use in Adrenocortical Carcinoma with Encouraging Results- a Case Report

Adrenocortical carcinoma (ACC) is a rare cancer with a very poor prognosis with median survival of around 17 months. We present a patient with metastatic ACC in whom the response to PD1 inhibitor pembrolizumab has been promising. Case report: A Caucasian female patient presented at the age of 19 y with weight gain, hypertension, moon facies, supraclavicular fullness and increased hair growth on her upper back. Serum potassium concentration was 2.6 mmol/l, cortisol was 46 mcg/dL (nl = 3-12mcg/dL), and plasma ACTH concentration was < 5 pg/ml (nl = 6-58pg/ml). CT abdomen revealed a 5.4 cm right adrenal mass. For ACTH-independent Cushing’s Syndrome, she underwent right adrenalectomy within 1 week of presentation. Pathology revealed a 6.5 cm ACC with negative margins, with sinusoidal invasion, but no vascular or capsular invasion. Mitosis rate was 15-20/HPF with atypical mitotic figures. Immunohistochemistry showed no loss of expression of mismatch repair gene products associated with microsatellite instability. She was unable to tolerate mitotane. Genetic analysis was negative for TP53 mutation, and she underwent radiation to the adrenal bed within 6 months following adrenalectomy. She remained without biochemical or structural evidence of disease recurrence until 2.5 years following adrenalectomy, when AM cortisol was 6 mcg/dL (nl < 1.8) after 1 mg and after 2 mg of dexamethasone the previous evening. CT scan of the pelvis, abdomen, and chest revealed 5 solid masses scattered within the lungs. The largest of these being 2.3 cm and 2 cm, and the other 3 being approximately 1 cm. Fine needle aspiration biopsy of the lung lesion revealed ACC metastases. Immunotherapy with pembrolizumab 200 mg every 3 weeks was initiated and continued for 2 years, with a side effect being grade 1 diarrhea. At 1 year after initiating pembrolizumab, she developed primary adrenal insufficiency that is being treated with 0.1 mg/d of fludrocortisone and low dose glucocorticoid replacement (hydrocortisone: 10mg in the morning and 5 mg in the evening), to avoid immune suppression. Pulmonary nodules decreased in size to 6 mm over the 2 years of pembrolizumab therapy and remained stable in size 1 year following completion of pembrolizumab therapy at which time the early morning serum cortisol concentration remained undetectable with a plasma ACTH concentration of 1177 pg/ml (nl = 6-50 pg/ml). In summary, this patient with ACC with normal mismatch repair gene expression demonstrated both structural and biochemical responses to 2 years of pembrolizumab therapy. The major side effect has been primary adrenal insufficiency. The biochemical and structural responses have been durable for 1 year after completion of pembrolizumab therapy. Conclusion: This patient with microsatellite stable ACC has had a 36-month response to pembrolizumab.