Immune-related adverse events

Immune checkpoint inhibitors (e.g. ipilimumab, pembrolizumab, nivolumab, avelumab, atezolizumab, durvalumab and cemiplimab) are forms of immunotherapy which work by stimulating the immune system (T-cells) to fight cancer and have been associated with substantial improvements in the prognosis of the disease. These drugs are associated with a unique spectrum of side effects termed 'Immune-related Adverse Events (irAEs)'. Patients receiving these drugs may develop immune-related adverse reactions (irARs) during treatment or several months after the last dose of the drug. Most of these reactions are reversible and managed with interruptions of treatment, administration of corticosteroids and/or supportive care. 

The incidence of irARs has been observed to be higher in patients receiving combination therapy compared with single agent treatment. There has also been substantial growth in the use of immunotherapy as part of cancer treatment in combination with chemotherapy and/or immunostimulatory agents (e.g. monoclonal antibodies) further enhancing the potential for toxicity.

Common side effects of immunotherapy

The following is not an exhaustive list, but some common side effects of immunotherapy include:

• Respiratory problems (pneumonitis) - symptoms may include shortness of breath, chest pain, new or worsening cough.
• Gastrointestinal problems (colitis) - signs and symptoms may include diarrhoea or increased number of bowel movements; stools that are black, tarry, sticky, or have blood or mucus; or severe abdominal pain / tenderness.
• Hepatic problems (hepatitis) - signs and symptoms may include jaundice, nausea and vomiting, abdominal pain, dark urine or bleeding / bruising.
• Endocrinopathies which include hypophysitis, type 1 diabetes mellitus, diabetic ketoacidosis, hypothyroidism and hyperthyroidism. Long term therapy may be necessary in cases of irreversible immune-related endocrinopathies. 
• Renal problems (nephritis).
• Dermatological problems - skin rash (can be severe) and pruritis.
• Cardiac problems (myocarditis) - signs and symptoms such as fatigue, chest pain, shortness of breath, palpitations, peripheral oedema or hypotension should prompt immediate clinical evaluation.
• Rheumatic problems - symptoms may include arthralgia, arthritis, musculoskeletal and back problems.
• Neurological problems - although one of the more rare side effects, there is the potential for significant morbidity and mortality. Patients may present with muscle weakness, blurring of vision, diplopia, limb weakness, headaches, altered cognition or consciousness levels.

Management

The management of any suspected irAR is complex and requires specialist advice from the relevant clinical team. Adequate evaluation must be performed to confirm aetiology or exclude other causes. The approach to the management of specific toxicities is discussed in the individual sections of the West of Scotland guideline for the Management of Immune-related Adverse Events. This is available on the WoSCAN intranet site / Guidelines and Protocols / Supportive Care subsection (link only active if accessing via NHS network). 

Corticosteroid dosing guidance and dose tapering regimens, as well as monitoring and cautionary advice are provided in the full guideline (see link above) on page 25 and in appendices 1 and 2.

Guideline reviewed: June 2023

Page last updated: December 2023