Association of peripheral edema with immune checkpoint inhibitors: A systematic review.

187 Background: Immune checkpoint inhibitors (ICIs) are widely used to treat patients with cancer but immune-related adverse events occasionally disrupt treatments and affect their quality of life. Peripheral edema from ICI therapy appears rare but can occur due to increased peripheral vascular permeability. Thus, we aimed to report the incidence and outcomes of peripheral edema from ICIs. Methods: Medline, Embase, and Web of Science were searched to identify phase 3 randomized controlled trials (RCTs) reporting the incidence of peripheral edema in patients treated with ICIs. We calculated the incident rate of peripheral edema based on treatment patterns (monotherapy and combination therapy) and ICI subtypes (PD-1, PD-L1, and CTLA-4 inhibitors). We also performed a systematic review to identify articles reporting treatment outcomes of peripheral edema from ICIs. Results: Overall, 60 RCTs comprising 22,590 patients were identified for the incidence analysis. Treatment-related peripheral edema (Grade 1-5) occurred in 2.8% from ICI monotherapy (n = 195/6969; PD-1 inhibitors: 2.2% [n = 104/4694], PD-L1: 3.7% [n = 58/1557], CTLA-4: 4.6% [n = 33/718]), 5.0% (n = 112/2257) from ICI with chemotherapy, and 8.7% (n = 205/2349) from ICI with molecular-targeted therapy. Grade 3-5 treatment-related peripheral edema occurred in 0.3% of patients treated with ICI monotherapy (Table). For treatment outcomes of peripheral edema, a systematic review identified 19 studies (17 case reports/series,1 phase 1/2 clinical trial, 1 pharmacovigilance study) comprising 40 patients with immune-related peripheral edema. In total, 82.5% (n = 33/40) of cases received glucocorticoid treatment, and 55.0% (n = 22/40) required a high dose (≥ 1 mg/kg/day) of prednisone. ICI was discontinued in 77.5% (n = 31/40) due to peripheral edema (permanent discontinuation in 35% [n = 14/40]). Conclusions: Peripheral edema occasionally occurs in patients treated with ICIs but its occurrence often requires glucocorticoid administration, which may impact cancer treatment outcomes. [Table: see text]