Immunotherapy-induced isolated ACTH deficiency in cancer therapy.

Abstract

Central adrenal insufficiency (AI) due to isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) has been recently associated with immune checkpoint inhibitor (ICI) therapy. Our aim was to analyze the prevalence, clinical characteristics, and therapeutic outcomes in cancer patients with IAD induced by ICI therapy. A retrospective and multicenter study was performed. From a total of 4447 cancer patients treated with ICI antibodies, 37 (0.8%) (23 men (62.2%), mean age 64.7 ± 8.3 years (range 46-79 years)) were diagnosed with IAD. The tumor most frequently related to IAD was lung cancer (n = 20, 54.1%), followed by melanoma (n = 8, 21.6%). The most common ICI antibody inhibitors reported were nivolumab (n = 18, 48.6%), pembrolizumab (n = 16, 43.2%), and ipilimumab (n = 8, 21.6%). About half of the patients (n = 19, 51.4%) had other immune-related adverse events, mainly endocrine adverse effects (n = 10, 27.0%). IAD was diagnosed at a median time of 7.0 months (IQR, 5-12) after starting immunotherapy. The main reported symptom at presentation was fatigue (97.3%), followed by anorexia (81.8%) and general malaise (81.1%). Mean follow-up time since IAD diagnosis was 15.2 ± 12.5 months (range 0.3-55 months). At last visit, all patients continued with hormonal deficiency of ACTH. Median overall survival since IAD diagnosis was 6.0 months. In conclusion, IAD is a rare but a well-established complication associated with ICI therapy in cancer patients. It develops around 7 months after starting the treatment, mainly anti-PD1 antibodies. Recovery of the corticotropic axis function should not be expected.

• Authors: Pedro Iglesias, Inmaculada Peiró, Betina Biagetti, Miguel Paja-Fano, Diana Ariadel Cobo, Carlos García Gómez, Manuel Mateu-Salat, Idoia Genua, Margarita Majem, Mariona Riudavets, Javier Gavira, Cristina Lamas, Antía Fernández Pombo, Fernando Guerrero-Pérez, Carles Villabona, José Manuel Cabezas Agrícola, Susan M Webb, Juan J Díez
• Journal: Endocrine-related cancer (Endocr Relat Cancer) Vol. 28 Issue 12 Pg. 783-792 (10 27 2021) ISSN: 1479-6821 [Electronic] England
• PMID: 34609950 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Ipilimumab
• Nivolumab
• Adrenocorticotropic Hormone

Topics

• Adrenocorticotropic Hormone (deficiency)
• Aged
• Endocrine System Diseases
• Genetic Diseases, Inborn
• Humans
• Hypoglycemia
• Immunotherapy (adverse effects)
• Ipilimumab (adverse effects)
• Male
• Melanoma (drug therapy)
• Middle Aged
• Nivolumab (adverse effects)
• Retrospective Studies