Hypophysitis caused by ipilimumab in cancer patients: hormone replacement or immunosuppressive therapy

• Published in: Experimental and clinical endocrinology & diabetes Vol. 121; no. 10; p. 581
• Main Authors: Lammert, A, Schneider, H J, Bergmann, T, Benck, U, Krämer, B K, Gärtner, R, Metzner, C, Schöfl, C, Berking, C
• Format: Journal Article
• Language: English
• Published: Germany 01-11-2013
• Subjects: Adrenal Cortex Hormones - adverse effects; Adrenal Cortex Hormones - therapeutic use; Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Female; Hormone Replacement Therapy - adverse effects; Humans; Immunosuppression - adverse effects; Ipilimumab; Melanoma - diagnostic imaging; Melanoma - drug therapy; Middle Aged; Neoplasm Metastasis; Pituitary Diseases - chemically induced; Pituitary Diseases - diagnostic imaging; Radiography
• ISSN: 1439-3646
• DOI: 10.1055/s-0033-1355337

Ipilimumab is besides the BRAF inhibitor vemurafenib the first officially approved medical treatment for metastatic melanoma, which results in improved survival. Ipilimumab leads to a release of a CTLA4-mediated inhibition of T-cell immunoreactions. Therefore, patients may also suffer from immune-related adverse events affecting different organs, which are typically treated by high-dose corticosteroids. Ipilimumab-induced hypophysitis (iH) has been reported in up to 17% of melanoma patients in clinical trials.Here we present 5 patients with metastatic melanoma and 2 patients with prostate cancer who developed hypophysitis after ipilimumab therapy. Patients were treated by high-dose corticosteroid therapy resulting in the resolution of local inflammation but not of pituitary deficiencies. Partial or complete hypopituitarism remained in all patients. Pharmacotherapy with high-dose corticosteroids caused complications in 5 patients, necessitating hospitalization in 4. 2 of the 3 patients with progressive disease died, while 3 patients had stable disease and 1 patient showed tumor regression after discontinuation of ipilimumab.In summary, with regard to safety and simplicity of hormonal substitution therapy we have to scrutinize high-dose corticosteroid therapy, though it only improves inflammation but not neuro-endocrine function and may cause further morbidity. Regression of the tumor depends on the ipilimumab-mediated immune events, in which high-dose and long-term corticosteroid therapy for iH appears to be counter-intuitive. Herein, we discuss screening and the diagnostic as well as therapeutic management of iH in metastatic cancer patients from an endocrinologic perspective.