Thyroid atrophy and pancreatic involution after cancer Immunotherapy.

Haupt, Fabian; Prosch, Helmut; Ebner, Lukas (2020). Thyroid atrophy and pancreatic involution after cancer Immunotherapy. RöFo. Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 192(7), pp. 688-690. Thieme 10.1055/a-1108-1934

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During the past decade, immunotherapy gained significant importance in the therapy of metastatic cancer. Immunotherapy has been first established in metastatic melanoma, a disease where no promising therapeutic option was previously available. Following the positive trial results, T-cell targeted immunotherapies have been established as a main foundation in therapy of systemic metastatic melanoma in clinical guidelines.

State-of-the-art immunotherapies comprise monoclonal antibodies, acting as checkpoint inhibitors blocking T-cell surface receptors, acting as negative regulators for T-cell activity. This maintains and/or reactivates cytotoxic T-cell activity.

Initial trials with Ipilimumab, targeting Cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) have shown an increased overall survival (OS) in patients with metastatic melanoma, but also drug related adverse events, potentially leading to the death of patients (14 of 643 patients, 2.2 %); approximately half (n = 7) of those incidents are immunotherapy-related (predominantly colitis with sepsis and/or perforation, apart from hepatic or neurological complications) (Hodi, F. S. et al. Improved survival with ipilimumab in patients with metastatic melanoma. The New England journal of medicine 363, 711–723, doi:10.1056/NEJMoa1003466 (2010).

Nivolumab, targeting the programmed death 1 (PD-1) surface protein is another promising check point inhibitor, with a remarkable impact on OS and progression free survival (PFS). A larger phase 3 trial has shown, has shown a better recurrence-free survival and far less adverse events (14.4 vs. 45.9 %) for Nivolumab, compared to CTLA-4 inhibitor Ipilimumab (Weber J. et al. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. N Engl J Med 2017; 377: 1824–1835).

We report a case of a 72 year old male patient with metastatic melanoma, who underwent a combined immunotherapy with Ipilimumab and Nivolumab, as well as a maintenance therapy with Nivolumab alone – leading to a stable remission of the metastatic disease – who developed thyroid atrophy with confirmed hypothyreosis, pancreatic atrophy with aggravation of a pre-existing diabetes and an immobilizing polyarthritis.

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