Immunotherapy-Related Adverse Events (irAEs)

#med

Cutaneous irAEs:

UTD
Most common adverse events associated with Immune Checkpoint Inhibitor (ICI) therapy
- Occurring in up to 50 percent of patients treated with monotherapy and 70 percent of patients treated with combination therapy.
Most commonly as inflammatory skin reactions (eg: maculopapular (picture 2A), lichenoid, psoriasiform (picture 4), eczematous reactions (picture 3))

UTD
Prevalence:
- Overall = ~5%
- PD1/PDL1 = ~3%
- ICI combination that includes an anti-CTLA-4 antibody = ~10%

Thyroid:
- Thyroid function should be monitored prior to each dose of an ICI.
- Autoimmune thyroid disease can be manifested as primary hypothyroidism secondary to a destructive thyroiditis or as hyperthyroidism associated with Graves disease.
Hypophysitis:
- Presents w/ pan-hypopituitarism (deficits of ACTH, TSH, FSH/LH, Growth hormone, prolactin)
- Laboratory workup needed to distinguish this from primary adrenal insufficiency/primary hypothyroid
- The diagnosis of hypophysitis is often supported radiographically by enhancement and swelling of the pituitary gland on magnetic resonance imaging of the brain
Adrenal insufficiency:
- 2/2 autoimmune adrenalitis
- Rare, reported in 0.7 percent of patients treated in randomized clinical trials
DM1:
- Rare, occurring in 0.2-0.9% of cases
- In contrast to other immune-related adverse events, treatment with glucocorticoids or other immunosuppressive agents is not effective in these patients, due to the almost complete destruction of the pancreatic beta cells by immunotherapy

Case series suggest that neurotoxicity occurs in approximately 1 to 14 percent of patients, with the highest rates associated with the use of combined immunotherapy using nivolumab plus ipilimumab
Neurologic complications associated with more severe toxicity include Guillain-Barré syndrome and myasthenia gravis. In some cases, myasthenia gravis may co-occur with inflammatory myositis and myocarditis and is associated with high fatality rates