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Marked Response of Hypermutated ACTH-Secreting Pituitary Carcinoma to Ipilimumab and Nivolumab

In this case, a 40-year-old female with Cushing’s was being treated at Memorial Sloan Kettering Cancer Center (MSK) in NYC for an aggressive ACTH-secreting pituitary carcinoma.  She had tried several treatments including multiple surgeries, radiation, and chemotherapy.  It had metastasized to her liver, and the pituitary tumor was producing ACTH at extremely high levels – 45,550 pg/mL at its worst, with a normal high level being 50 pg/ml.

Dr. Eliza Geer and her team at MSK had noticed that patients receiving a type of immunotherapy called checkpoint inhibitors for other types of cancers frequently had pituitary inflammation as a side effect of the therapy.  Checkpoint inhibitors work by removing a cancer cell’s “brake” on the immune cell that prevents it from destroying the cancer.  The doctors at MSK postulated that the treatment must be targeting proteins in the pituitary cells, and that made them think that this type of therapy might have some effect on pituitary tumors.  The patient in this case had amazing shrinkage of both her pituitary and liver tumors on the two-drug therapy. 

This is the first reported use of immunotherapy to treat pituitary tumors.  In addition to that result, samples of the patient’s tumors were taken and analyzed for gene mutations: the pituitary tumor before she received chemotherapy, and the liver tumor after chemo.  The liver tumor had many mutations that the pituitary tumor did not.  This led the researchers to consider that the hypermutation of the original tumor cells was perhaps caused by the chemo and that mutated tumors might be more responsive to immunotherapy.

This case has led the team at MSK to embark on a clinical trial in hopes of good response to this type of treatment for pituitary tumors.  The patient is doing better and currently only takes one form of checkpoint inhibitor immunotherapy.  For the full story, some impressive photos of tumors before and after treatment, and an excellent short video about how immunotherapy works, scan the QR code or visit

Lin AL, Jonsson P, Tabar V, Yang TJ, Cuaron J, Beal K, Cohen M, Postow M, Rosenblum M, Shia J, DeAngelis LM, Taylor BS, Young RJ, Geer EB.  Journal of Clinical Endocrinology and Metabolism.  2018 Oct 1;103(10):3925-3930. doi: 10.1210/jc.2018-01347

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