Prevalence of hypophysitis in a cohort of patients with metastatic melanoma and prostate cancer treated with ipilimumab

Brilli, Lucia; Danielli, Riccardo; Ciuoli, Cristina; Calabrò, Luana; Giacomo, Anna Maria Di; Cerase, Alfonso; Paffetti, Patrizia; Sestini, Fausta; Porcelli, Brunetta; Maio, Michele; Pacini, Furio

doi:10.1007/s12020-017-1289-2

Cited by 40 publications

(30 citation statements)

References 12 publications

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“…However, their use is associated with broad immunological adverse events, such as enterocolitis, hypophysitis, and pancreatitis [1, 2, 3, 4]. Notably, enterocolitis has been reported in up to approximately 8$ of patients who have received ipilimumab [5].…”

Section: Discussionmentioning

confidence: 99%

Severe Gastritis after Administration of Nivolumab and Ipilimumab

et al. 2018

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Immune checkpoint inhibitors such as ipilimumab, a cytotoxic T-lymphocyte-associated antigen-4 inhibitor, have been widely used for advanced malignancies. As these inhibitors improve antitumor immunity via T-cell modulation, immune-mediated adverse events associated with T-cell activation, such as colitis, might occur. Herein, we describe a 75-year-old Japanese woman with metastatic malignant melanoma who developed hemorrhagic gastritis after ipilimumab treatment. There was no macroscopic or clinical improvement of gastritis after proton pump inhibitor treatment. However, her condition improved after approximately 3 weeks of corticosteroid therapy and Helicobacter pylori eradication. This case suggests a potential association between severe gastritis and immune checkpoint inhibitor treatment. Although several reports have mentioned ipilimumab-associated colitis, gastritis is considered to be rare. In the present case, H. pylori-associated gastritis might have been exacerbated by the T-cell modulation effect of ipilimumab. To date, no report has clarified the mechanism by which ipilimumab modifies H. pylori infection. The present treatment course provides a helpful perspective for similar cases.

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Section: Discussionmentioning

confidence: 99%

Severe Gastritis after Administration of Nivolumab and Ipilimumab

et al. 2018

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“…Hepatitis and hypophysitis are also adverse events related to immunotherapy (14)(15)(16). Hypothetically, activation of the immune system could result in increased 18 F-FDG activity in the spleen.…”

Section: Discussionmentioning

confidence: 99%

¹⁸F-FDG PET/CT Can Predict Development of Thyroiditis Due to Immunotherapy for Lung Cancer

Eshghi

Garland

Nia

et al. 2018

J. Nucl. Med. Technol.

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Our primary purpose was to determine whether increased F-FDG uptake in the thyroid gland predicts development of thyroiditis with subsequent hypothyroidism in patients undergoing immunotherapy with nivolumab for lung cancer. Secondarily, we determined whetherF-FDG uptake in the thyroid gland correlates with number of administered cycles of nivolumab. Retrospective chart review over 2 y found 18 lung cancer patients treated with nivolumab who underwentF-FDG PET/CT before and during therapy. SUV, SUV, and total lesion glycolysis of the thyroid gland were measured. SUVs were also measured for the pituitary gland, liver, and spleen. Patients underwent monthly thyroid testing. PET/CT parameters were analyzed by unpaired testing for differences between 2 groups (patients who developed hypothyroidism and those who did not). Correlation between development of thyroiditis and number of cycles of nivolumab was also tested. Six of 18 patients developed hypothyroidism. The test comparing the 2 groups demonstrated significant differences in SUV ( = 0.04), SUV ( = 0.04), and total lesion glycolysis ( = 0.02) of the thyroid gland. Two of 4 patients who developed thyroiditis and had increased F-FDG uptake in the thyroid gland had a normal TSH level at the time of follow-upF-FDG PET/CT. Patients who developed thyroiditis with subsequent hypothyroidism stayed longer on therapy (10.6 cycles) than patients without thyroiditis (7.6 cycles), but the trend was not statistically significant. No significant difference in PET/CT parameters was observed for pituitary gland, liver, or spleen. F-FDG PET/CT can predict the development of thyroiditis with subsequent hypothyroidism before laboratory testing. Further study is required to confirm the positive trend between thyroiditis and duration of therapy.

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“…Hence, normal imaging of the pituitary does not ex-clude its diagnosis [27]. Corticotropic, thyrotropic and gonadotropic functions are mostly affected, but long term failure of the corticotropic axis is paramount [10,25,112]. High-dose glucocorticoids are proposed for those with mass effect symptoms, such as severe headache or visual-field disturbance [27,113,114].…”

Section: Hypophysitismentioning

confidence: 99%

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2019

Horm Metab Res

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Monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4), programed cell death 1 (PD-1), or its ligand (PD-L1) have become the mainstay for advanced malignancies. The incidence of endocrine adverse events provoked by these immune checkpoint inhibitors (ICI) is based on data from randomized controlled trials, which have their drawbacks. PubMed was searched through August 22nd, 2017, by 2 reviewers independently (J.d.F. and C.E.A.). Early phase I/II, phase III experimental trials, prospective and retrospective observational studies were included. The weighted incidence and risk ratio were estimated for hypophysitis, primary thyroid disease, primary adrenal insufficiency, and diabetes mellitus. Their management is discussed in a systematic review. A total of 101 studies involving 19 922 patients were included. Ipilimumab-treated patients experienced hypophysitis in 5.6 % (95 % CI, 3.9-8.1), which was higher than nivolumab (0.

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Prevalence of hypophysitis in a cohort of patients with metastatic melanoma and prostate cancer treated with ipilimumab

Cited by 40 publications

References 12 publications

Severe Gastritis after Administration of Nivolumab and Ipilimumab

Severe Gastritis after Administration of Nivolumab and Ipilimumab

¹⁸F-FDG PET/CT Can Predict Development of Thyroiditis Due to Immunotherapy for Lung Cancer

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Prevalence of hypophysitis in a cohort of patients with metastatic melanoma and prostate cancer treated with ipilimumab

Cited by 40 publications

References 12 publications

Severe Gastritis after Administration of Nivolumab and Ipilimumab

Severe Gastritis after Administration of Nivolumab and Ipilimumab

18F-FDG PET/CT Can Predict Development of Thyroiditis Due to Immunotherapy for Lung Cancer

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¹⁸F-FDG PET/CT Can Predict Development of Thyroiditis Due to Immunotherapy for Lung Cancer