Management of Immune-Related Adverse Events in Cancer Therapy

Immune checkpoint inhibitors have transformed the treatment landscape for many malignancies by releasing the brakes on T-cell activity. However, this immunological unleashing can lead to off-target inflammation in diverse tissues, termed immune-related adverse events (irAEs). Clinical manifestations range from mild dermatitis or colitis to life-threatening myocarditis or pneumonitis, with onset varying from weeks to months after therapy initiation and, in some cases, even after treatment cessation. Effective management hinges on early recognition through systematic monitoring, grading of severity, and prompt intervention. Mild irAEs may be managed with symptomatic care and temporary treatment delay, whereas moderate to severe events often require systemic corticosteroids followed by careful tapering. Organ-specific algorithms guide the use of additional immunosuppressive agents—such as tumour necrosis factor-alpha antagonists for steroid-refractory colitis or mycophenolate mofetil for hepatitis—while preserving antitumour efficacy. Multidisciplinary collaboration among oncologists, organ specialists and nursing teams underpins successful outcomes. Emerging strategies include biomarker-driven risk stratification, patient education initiatives to promote early reporting of symptoms, and telemedicine platforms to facilitate remote monitoring. Balancing the therapeutic benefits of checkpoint blockade against the potential for irAEs remains a central challenge in personalised cancer immunotherapy.

Research from Nature Portfolio

Recent studies have dissected the complex biology and clinical management of irAEs, emphasising areas of ongoing debate and research opportunity. Investigators have mapped the spectrum of organ involvement and highlighted variability in onset, severity and resolution across different checkpoint targets. Crucial knowledge gaps have been identified in predicting which patients will develop severe irAEs and in optimising the timing and dosing of immunosuppression to limit toxicity without compromising antitumour responses. Controversies around rechallenge with checkpoint inhibitors after high-grade events have spurred calls for prospective trials to establish evidence-based rechallenge protocols. Novel frameworks have been proposed for integrating real-world data into adaptive management pathways, with the aim of refining clinical decision-making and individualising irAE prevention and treatment.

Management of Immune-Related Adverse Events in Cancer Therapy publication trend

The graph below shows the total number of articles in management of immune-related adverse events in cancer therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Immune-related adverse event (irAE): an unintended inflammatory reaction in normal tissues triggered by immune checkpoint blockade.

Immune checkpoint inhibitor (ICI): a monoclonal antibody that blocks regulatory molecules on T cells, enhancing antitumour immunity.

Cytotoxic T-lymphocyte antigen 4 (CTLA-4): a checkpoint receptor on T cells whose blockade promotes early T-cell activation.

Programme death-1 (PD-1)/PD-L1 pathway: an inhibitory axis between T cells and tumour cells or antigen-presenting cells; its inhibition sustains peripheral T-cell activity.

Cytokine-release syndrome (CRS): a systemic inflammatory response characterised by fever, hypotension and elevated cytokines, sometimes seen with immunotherapies.

Pseudoprogression: a transient radiological increase in tumour burden due to immune infiltration rather than true disease growth.

References

1. Patterns of toxicity burden for FDA-approved immune checkpoint inhibitors in the United States. Journal of Experimental & Clinical Cancer Research (2023).
2. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. Journal for ImmunoTherapy of Cancer (2017).
3. Delayed immune-related events (DIRE) after discontinuation of immunotherapy: diagnostic hazard of autoimmunity at a distance. Journal for ImmunoTherapy of Cancer (2019).
4. Incidence rates of immune-related adverse events and their correlation with response in advanced solid tumours treated with NIVO or NIVO+IPI: a systematic review and meta-analysis. Journal for ImmunoTherapy of Cancer (2019).
5. Immune-related adverse events and the balancing act of immunotherapy. Nature Communications (2022).