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Immune-related adverse events from checkpoint inhibitors: An evidence-based management review
Fausto Petrelli1, Lorenzo Dottorini1, Mauro Rossitto1
1Oncology Unit, ASST Bergamo Ovest, Treviglio, BG, Italy.
Immune checkpoint inhibitors (ICIs) improve cancer outcomes but can cause immune‑related adverse events (irAEs) in any organ. Corticosteroids remain first‑line, achieving remission in ∼70-85%: grade 2 toxicities typically use oral prednisone 0.5-1 mg/kg/day, while grade 3-4 require IV methylprednisolone 1-2 mg/kg/day (or pulses for life‑threatening disease). However, 20-40% of severe irAEs are steroid‑refractory and need rapid, organ‑directed escalation-mycophenolate for hepatitis/pneumonitis; infliximab or vedolizumab for colitis; IVIG and plasma exchange for neurologic syndromes; and investigational abatacept for myocarditis, which carries ∼35-50% mortality and demands aggressive multidisciplinary care. Emerging salvage options include JAK inhibitors (≈70.8% response in grade ≥3 refractory cases), extracorporeal photopheresis, and targeted cytokine blockade. Long‑term issues include chronic sequelae (≈40-50%), surveillance, and complex ICI rechallenge decisions, especially in elderly patients and those with autoimmune disease. Prospective trials, standardized monitoring, and predictive biomarkers are urgently needed. As ICIs move into curative-intent settings, optimizing irAE care preserves safety and treatment continuity.
Immune checkpoint inhibitors (ICIs) improve cancer outcomes but can cause immune‑related adverse events (irAEs) in any organ. Corticosteroids remain first‑line, achieving remission in ∼70-85%: grade 2 toxicities typically use oral prednisone 0.5-1 mg/kg/day, while grade 3-4 require IV methylprednisolone 1-2 mg/kg/day (or pulses for life‑threatening disease). However, 20-40% of severe irAEs are steroid‑refractory and need rapid, organ‑directed escalation-mycophenolate for hepatitis/pneumonitis; infliximab or vedolizumab for colitis; IVIG and plasma exchange for neurologic syndromes; and investigational abatacept for myocarditis, which carries ∼35-50% mortality and demands aggressive multidisciplinary care. Emerging salvage options include JAK inhibitors (≈70.8% response in grade ≥3 refractory cases), extracorporeal photopheresis, and targeted cytokine blockade. Long‑term issues include chronic sequelae (≈40-50%), surveillance, and complex ICI rechallenge decisions, especially in elderly patients and those with autoimmune disease. Prospective trials, standardized monitoring, and predictive biomarkers are urgently needed. As ICIs move into curative-intent settings, optimizing irAE care preserves safety and treatment continuity.
