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

• Main Authors: Manon Levy, Juliette Abeillon, Stéphane Dalle, Souad Assaad, Françoise Borson-Chazot, Emmanuel Disse, Gérald Raverot, Christine Cugnet-Anceau
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: Journal of Clinical Medicine
• Subjects: hypophysitis; adrenal insufficiency; immunotherapy; nivolumab; pembrolizumab; programmed cell death 1 protein
• Online Access: https://www.mdpi.com/2077-0383/9/10/3280

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 (<i>n</i> = 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.