Hypophysitis Caused by Ipilimumab in Cancer Patients: Hormone Replacement or Immunosuppressive Therapy

Abstract

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.

18F-FDG PET/CT and Melanoma: Staging, Immune Modulation and Mutation-Targeted Therapy Assessment, and Prognosis

“…Immunomodulation therapy, which potentiates T lymphocytes, is known to produce a high rate (up to 70%) of adverse immune-related reactions, including colitis, dermatitis, hypophysitis, arthritis, and thyroiditis (Fig. 6), which can lead to false findings on FDG PET [47, [76][77][78][79][80][81][82]. Moreover, melanoma treated with ipilimumab will commonly progress before the documented response [52], further complicating assessments of therapy response.…”

“…7-9). The preponderance of published data regarding the utility of FDG PET and FDG PET/CT for monitoring treatment response to immunomodulation therapy are case reports that illustrate radiologic features of the immunerelated adverse reactions and highlight the challenges of monitoring immunomodulation therapy response with FDG PET/CT [77,[79][80][81][82][83][84][85][86][87][88]. Lyall et al [86] reported on a 52-year-old woman whose course of ipilimumab was cancelled after she developed watery diarrhea, sweats, and chills.…”

Ipilimumab‐induced hypophysitis in melanoma patients: an Australian case series

“…Immunosuppressive glucocorticoids may be indicated, however, if vision is compromised . Failure to appreciate the lack of benefit of high‐dose glucocorticoid therapy in reversing hypophysitis may also result in an adrenal crisis when glucocorticoid therapy is (inappropriately) withdrawn . Thus, our cases suggest that immunosuppressive glucocorticoid therapy may not be necessary, and may only be required for patients with visual disturbance due to pituitary enlargement.…”

Autoimmune hypophysitis: a study of natural course

“…Hypophysitis has been reported in up to 17% melanoma cases treated with ipilimumab. 5 With the increasing use of ipilimumab in the treatment of melanoma, addition of these iatrogenic autoimmune hypophysitis cases may further increase the incidence of autoimmune hypophysistis.…”