Edema and serositis as an adverse event in patients with cancer receiving immune checkpoint blockade: Systematic review to evaluate this immune-related adverse event and associated treatment strategies.

Abstract

2649 Background: Immune checkpoint blockade (ICB) is a standard therapeutic option for certain patients with solid tumors, often leading to durable responses. Immune-related adverse events (irAEs) can impact treatment duration and patients' quality of life. The mechanism of irAEs is proposed to be an inflammatory response triggered by blocking immune checkpoints, and nonspecific symptoms like edema and fluid accumulation can occur. We performed a systematic review to summarize reported studies evaluating edema and serositis to explore edema and serositis as an irAE and management strategies. Methods: We performed a database search in Medline, Embase, and Web of Science for studies reporting the incidence and outcome of immune-related generalized edema (irGE) including peripheral edema, capillary leak syndrome, serositis, pleural/peritoneal/pericardial effusion, and anasarca as an irAE among patients with solid tumors treated with ICB. Two independent reviewers analyzed the eligibility of each article. Those that did not report outcomes related to irGE were excluded. The number of patients, cancer type, name and type of ICB, type of irGE, treatment of irGE, and treatment outcome for irGE were extracted from each article to summarize the characteristics of irGE. Results: 662 articles were identified, and 80 studies were included (65 case reports/series, 8 cohort studies, 3 phase 1/2 clinical trials) that described clinical characteristics and treatment outcomes for AEs from 196 patients, and 259 irGE incidences reported. The median age was 62 (Interquartile range: 55-68). 35.9% of cases were female (n=28/78). Commonly reported irGEs were pericardial effusion (n=115, 44.4%), pleural effusion (n=58, 22.4%), peripheral edema (n=40, 15.4%), and ascites (n=19, 7.3%). PD-1 blockade was utilized in 75.8% of cases, followed by PD-L1 blockade (14.9%) and dual ICB (CTLA4 and PD-1 blockade, 4.6%). Common cancers where irGE occurred were: lung cancer (63.9%), malignant melanoma (17.0%), and urothelial carcinoma (3.1%). We classified irGEs into primary irGE (n=84, 42.9%), secondary to other irAEs (n=41, 20.9%), secondary to pseudoprogression (n=14, 7.1%), and cancer progression (n=13, 6.6%). Glucocorticoid was used to manage irGEs in 91 patients (46.4%); 48 cases (24.5%) required the prednisone-equivalent dose of > 1 mg/kg/day. ICB discontinuation was confirmed in 96 cases (49.0%) among which 53 (27.0%) permanently stopped ICB use due to irGEs. Conclusions: irGE is an important irAE among patients with solid tumors receiving ICB. Most cases required glucocorticoid therapy along with discontinuation of ICB, which could result in poorer quality of life and potentially impact outcomes. The pathophysiology, incidence and clinical outcomes of irGE need to be accurately described in further studies.