Immune-Related Adverse Events of Checkpoint Inhibitors: Clinical Spectrum and Insights Across Major Malignancies

Abstract

Immune checkpoint inhibitors have transformed the management of solid and haematological malignancies by restoring antitumour T-cell activity through blockade of cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1, and programmed death-ligand 1. The same mechanism that enables tumour control disrupts peripheral immune tolerance, producing a heterogeneous family of toxicities termed immune-related adverse events. These events can affect almost any organ system, follow an unpredictable temporal course, and occasionally prove fatal, most notably in the case of myocarditis and fulminant colitis. This review synthesises the contemporary clinical, mechanistic, and management literature on immune-related adverse events, with particular attention to organ-specific presentations, the influence of underlying malignancy and treatment regimen on toxicity phenotype, and emerging biomarkers of risk. Cutaneous and gastrointestinal toxicities remain the most frequent manifestations, whereas endocrine, pulmonary, hepatic, cardiac, renal, neurological, rheumatological, haematological, and ocular events occur less often but carry disproportionate morbidity and, in selected cases, mortality. Patterns of toxicity differ meaningfully across melanoma, non-small cell lung cancer, renal cell carcinoma, and hepatocellular carcinoma, reflecting both the underlying tumour microenvironment and the specific checkpoint regimen employed. Corticosteroids remain the cornerstone of management, supplemented increasingly by biologic immunosuppressants for steroid-refractory disease, while rechallenge after toxicity resolution is feasible in many but not all circumstances. The relationship between toxicity and antitumour efficacy remains incompletely resolved, complicating decisions around treatment interruption. Advances in gut microbiome profiling, peripheral blood immune signatures, and pharmacovigilance methodology offer promising avenues toward individualised risk stratification. Continued multidisciplinary collaboration, standardised toxicity terminology, and longitudinal outcome data will be essential to refine the safe and durable use of checkpoint blockade across an expanding range of cancer types.