Capillary leak syndrome with immune checkpoint inhibitors and anti-cancer targeted therapy agents: Not that common

Capillary leak syndrome (CLS) is a rare condition typically presenting with profound hypotension, edema, and hemoconcentration. While there are some known, yet rare causes of CLS described, there is very limited data available with use of monoclonal antibodies and immune checkpoint inhibitors. This study aimed to look for the reported side effect of CLS with the use of targeted monoclonal antibodies and immune checkpoint inhibitors (ICI). FDA adverse event reporting system (FAERS) database was searched from first quarter 2010 to fourth quarter 2021 for targeted monoclonal antibodies and ICI. Other literature search including PubMed and case reports/series were also performed. Only 22 cases of CLS with novel anti-cancer treatments were reported in FAERS. Anti-CD20 was the most common class with nine cases of CLS with Rituximab. Six cases with ICI and four cases of CLS with anti-VEGF therapy were also documented. PubMed search showed anti-programmed cell death protein 1 (anti-PD1) as the most common class associated with CLS with five reported cases. CLS is a known complication of anticancer agents such as gemcitabine, clofarabine, cyclophosphamide, platinum-based therapy, colony stimulating factors, and CAR-T therapy, however CLS is not that common with newer monoclonal antibodies and ICIs. This study demonstrates that clinicians need to be aware of this rare fatal side effect of these drugs.