Anti-PD1 and Anti-PDL1-Induced Hypophysitis: A Cohort Study of 17 Patients with Longitudinal Follow-Up

• Published in: Journal of clinical medicine Vol. 9; no. 10; p. 3280
• Main Authors: Levy, Manon, Abeillon, Juliette, Dalle, Stéphane, Assaad, Souad, Borson-Chazot, Françoise, Disse, Emmanuel, Raverot, Gérald, Cugnet-Anceau, Christine
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.10.2020; MDPI
• Subjects: adrenal insufficiency; Apoptosis; Cell death; Clinical medicine; Cohort analysis; Endocrinology; Hormones; Human health and pathology; Hyponatremia; hypophysitis; Immune system; Immunotherapy; Laboratories; Life Sciences; Ligands; Magnetic resonance imaging; Males; Monoclonal antibodies; nivolumab; Patients; pembrolizumab; programmed cell death 1 protein; Radiation therapy; Steroids; Testosterone; Thyroid gland; United States > US; Germany; pembrolizumab; adrenal insufficiency; programmed cell death 1 ligand 1 protein; nivolumab; programmed cell death 1 protein; immunotherapy; hypophysitis
• ISSN: 2077-0383; 2077-0383
• DOI: 10.3390/jcm9103280

Hypophysitis, secondary to programmed cell death 1 protein (PD1) and programmed cell death 1 ligand 1 (PDL1) inhibitors, were thought to be rare, with only a few studies describing more than one case with long-term follow-up. The aim of the present study was to describe the clinical, laboratory, and morphological characteristics of PD1/PDL1 inhibitor-induced hypophysitis, and its long-term course. This cohort study was conducted at the University Hospital of Lyon, France, with longitudinal follow-up of patients. Seventeen cases of PD1/PDL1 inhibitor-induced hypophysitis were included. The median time to onset of hypophysitis was 28 weeks (range: 10–46). At diagnosis, 16 patients complained of fatigue, 12 of nausea or loss of appetite, while headache was rare. We found no imaging pituitary abnormality. All patients presented adrenocorticotropic hormone (ACTH) deficiency; other pituitary deficiencies were less common (n = 7). At last follow-up (median: 13 months), ACTH deficiency persisted in all but one patient and one patient recovered from gonadotropic deficiency. PD1/PDL1 inhibitor-induced hypophysitis is a clinical entity different from those associated to cytotoxic T-lymphocyte antigen-4 (CTLA4) inhibitors, with less obvious clinical and radiological signs, and probably a different mechanism. The paucity of symptoms demonstrates the need for systematic hormonal follow-up for patients receiving PD1/PDL1 inhibitors.