Immune-related generalised oedema-A new category of adverse events with immune checkpoint inhibitors

Background: Generalised oedema was occasionally reported associated with im-mune checkpoint inhibitors (ICPIs). The purpose of this study is to investigate immune -related generalised oedema (ir-GE) drug related to ICPI, through frequency, clinical and path-ological characteristics, and patient's outcome.Patients and methods: Objectives of the study were to report on ir-GE associated with ICPI to define frequency, associated signs and symptoms, pathological characteristics, severity, and response to corticosteroids. To be included in the study, adult patients had to have ir-GE related to ICPI with certain or likely link, without any other known causes of generalised oedema. The study design was observational, over the period 2014-2020, from pharmacovigi-lance databases in France, including the prospective Registre des Effets Inde acute accent sirables Se acute accent ve`res des Anticorps Monoclonaux Immunomodulateurs en Cance acute accent rologie (REISAMIC) registry. Calculation of the frequency of ir-GE was restricted to the prospective REISAMIC registry.Results: Over 6633 screened patients, 20 had ir-GE confirmed drug related to ICPI. Based on the prospective REISAMIC registry, the frequency of ir-GE was 0.19% of ICPI-treated pa-tients (3 cases out of 1598 screened patients). The 20 patients with ir-GE had a median (range) age of 62 (26-81) years, most frequent tumour types were melanoma (n = 9; 45%) and lung cancer (n = 6; 30%). The most frequent localisations of oedema were peripheral (n = 17; 85%), pleural (n = 13; 65%), and peritoneal (n = 10; 50%). Polyserositis was observed in 11 (55%) patients. The median (range) weight gain per patient was 9 (2-30) kg. Associated signs and symptoms met criteria for capillary leak syndrome (n = 4; 20%), sinusoidal obstruc-tion syndrome/veno-occlusive disease (SOS/VOD) (n = 3; 15%), or subcutaneous autoim-mune syndrome (n = 2; 10%). Corticosteroids were administered to 15 patients; of them, 10 (67%) improved clinically after corticosteroids. Based on CTCAEV5.0, the highest severity of ir-GE was grade >4 in 11 (55%) patients and four (20%) patients died due to ir-GE.Conclusions: Generalised immune system-related oedema is a new category of adverse event with immune checkpoint inhibitors and is often associated with a life-threatening condition. The pathophysiology may in some cases be related to endothelial dysfunctions, such as SOS/VOD or capillary leak syndrome.(c) 2022 Elsevier Ltd. All rights reserved.