Immune-Related Adverse Events (irAEs) 
Definition: ...

Immune-Related Adverse Events (irAEs) 

Definition: systemic autoimmune or inflammatory events due to immune system activation by ICIs

Risk factors:

 • Combination immunotherapy (anti-CTLA-4+anti-PD-1): associated w/ earlier, higher incidence, and ↑severity; significantly less with anti-PD1 compared with anti-CTLA-4

 • No predictors of who will develop irAEs. Patients with pre-existing autoimmune disease can flare (see above).

Timing: Highly variable based on organ system involved, drug target, monotherapy vs combination. Can present over weeks to years.

Clinical presentation: Dermatologic toxicity (rash, vitiligo), hepatitis, thyroiditis, colitis, myocarditis, pneumonitis, DM1, neurotoxicity (aseptic meningitis, encephalitis, transverse myelitis, neuropathy/mononeuritis, GBS, myasthenia), arthralgias>arthritis, Sicca syndrome. See below for organ-specific details.

Treatment: Absence of prospective data, treatment recommendations based on expert consensus, see ASCO guidelines.

 • Systemic glucocorticoids (PO, IV) are first-line.

    o Other immunosuppressive agents are used in treatmentrefractory cases (infliximab [except hepatitis], MMF, tacrolimus, MTX

    o ATG, IVIG/plasmapheresis in autoAb-mediated/neurologic irAEs)

 • Can continue therapy with close monitoring for Grade 1 toxicities; hold for Grade 2, consider resuming if back to Grade 1

 • Grade 3 irAE (defined for each irAE) typically requires holding immunotherapy, generally rechallenge is not advised

 • Grade 4 irAE warrant permanent discontinuation of immunotherapy (except in endocrinopathies controlled with hormone replacement); in some cases, change to different agent may be safe

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