Consequences of adverse events in cancer immunotherapy combinations - a comprehensive real-world analysis

Immune checkpoint inhibitors (ICIs) are pivotal in systemic anticancer therapy. The aim of the study was to investigate incidence, severity and consequences of immune-related adverse events (irAEs) in ICI combinations by comparing different adverse events classification systems.

A retrospective multicentre cohort study included patients treated with ICI combinations. IrAEs were assessed by CTCAE v.5, NCC MERP index and SITC consensus for chronic irAEs.

Among 612 patients, 244 (40%) experienced 354 irAEs, in total 58 irAEs per 100 patients varying between treatments. Higher incidence was observed for autoimmune disease, thoracic radiotherapy, melanoma, dual ICI and ICI/TKI. Severe irAEs occurred in 147 patients, leading to treatment discontinuation and hospitalization in half of the patients. Chronic irAEs were common, with 64% persisting beyond three months after ICI discontinuation, 22% of these resolved (median 135 steroid days, 154 days to resolution). Common chronic toxicities included endocrine, pulmonary or rheumatic irAEs. Fatal irAEs affected 16 patients, primarily from pneumonitis, colitis or hepatitis.

NCC MERP better captured clinical consequences compared to CTCAE, while SITC criteria uniquely identified long-term irAEs. Severe and chronic irAEs were frequent, emphasizing the need for improved communication about irAE management and prospective studies with revised toxicity definitions.ClinicalTrials.govIDNCT06476158.