Capillary leak syndrome – rare complication of therapy with immune checkpoint inhibitor

Immune checkpoint inhibitors are relatively new and effective agents for treatment of malignant tumors, widely used to combat neoplasms of various locations. Nevertheless, these drugs can cause unwanted immune-mediated phenomena, one of which is capillary leak syndrome. Capillary leak syndrome is characterized by leakage of the liquid part of the plasma from the vascular lumen and is complicated by development of generalized edematous syndrome and hypovolemic shock. Although this complication is rare, it is associated with high risk of fatal outcome, and currently there are no established diagnostic and therapeutic approaches. The aim of our review was to present modern data on capillary leak syndrome caused by immune checkpoint inhibitors. We performed a search and comparative analysis of articles describing this complication. In the PubMed / Medline, Scopus, Web of Science, Google Scholar, and eLibrary databases, 30 clinical case descriptions from 2019 to 2025 were found, 25 of which were included in the review. Development of this complication was most often associated with the use of pembrolizumab (44 %). The median time to development was 12.7 weeks. In one patient, the complication developed against the background of tumor progression. Peripheral edema was described in 96 % of patients. Pleural effusion was the 2nd most common clinical manifestation (68 %). For the management of the complication, 1st-line systemic glucocorticoids were used in 80 % of patients, and they were effective in approximately one third of cases. 13 patients received 2nd-line immunosuppressants, mostly intravenous immunoglobulin. The mortality rate during follow-up was 28 %. With accumulating clinical experience of immune checkpoint inhibitor use, the spectrum and frequency of associated adverse events, including capillary leak syndrome, are expected to grow. This underscores the need to develop diagnostic and therapeutic strategies for this adverse reaction.