Thyroid atrophy and pancreatic involution after cancer Immunotherapy

Introduction

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.

Publication History

Article published online:
19 March 2020