Retrospective multicohort study of multi-organ immune-related adverse events for immune checkpoint inhibitors and their prognostic implications

Understanding co-occurrence patterns and prognostic implications of immune-related adverse events (irAEs) is crucial for immunotherapy management. Previous studies have been limited by sample size and generalizability. In a retrospective study in two cohorts of patients receiving immune checkpoint inhibitors in the USA, positive pairwise correlations of irAEs were commonly observed. Co-occurring irAEs were decomposed into seven factors across organs, revealing seven distinct patient clusters (endocrine, cutaneous, respiratory, gastrointestinal, hepatic, musculoskeletal, and neurological. Patient clusters that predominantly had endocrine and cutaneous irAEs had favorable overall survival outcomes at a 6-months landmark timepoint, while the cluster with respiratory irAEs had onfavorable survival outcomes, and the other clusters had neutral surival outcomes. The authors conclude that identifying the irAE cluster to which a patient belongs can provide valuable clinical information for prognosticating outcomes of immunotherapy.