Table IV.

Schematic treatment algorithm for management of pneumonitis, endocrinopathy and renal injury occurring as adverse events during anticancer immunotherapy.

A, Pneumonitis.
Severity of symptoms	Description	Management and follow-up
Grade 1	Asymptomatic; radiographic changes only	Continue ICPI
		Clinical or diagnostic observation
Grade 2	Symptomatic (mild to moderate new symptoms)	Delay ICPI 1 mg/kg/day methylprednisolone or PO equivalent Consider bronchoscopy and lung biopsy
Grade 3–4	Severe symptoms; worsening hypoxia; life-threatening	Discontinue ICPI 2–4 mg/kg/day methylprednisolone or i.v. equivalent Consider bronchoscopy and lung biopsy If symptoms are not improving within 48 h or are worsening: Consider alternative immunosuppressive therapy (such as mycophenolate mofetil, cyclophosphamide or infliximab)
B, Endocrinopathy.
Severity of symptoms	Description	Management and follow-up
Grade 1	Asymptomatic	Continue ICPI
		Hormone replacement
Grade 2	Symptomatic endocrinopathy	Delay ICPI
		1–2 mg/kg/day methylprednisolone i.v. or PO equivalent
Grade 3–4	Symptomatic endocrinopathy requiring urgent medical intervention, interfering with ADL. Grade 4: Life-threatening consequences (such as adrenal crisis)	Delay or discontinue ICPI 2 mg/kg/day methylprednisolone i.v. or equivalent If suspicion of adrenal crisis: stress dose of steroids with mineralocorticoid activity
C, Renal injury.
Severity of symptoms	Description	Management and follow-up
Grade 1	Creatinine 1.5× ULN	Continue ICPI
		Creatinine monitoring
Grade 2–3	Creatinine >1.5 to 6× ULN	Delay ICPI
		0.5–1 mg/kg/day methylprednisolone i.v. or equivalent
Grade 4	Creatinine >6× ULN	Discontinue ICPI
		1–2 mg/kg/day methylprednisolone i.v. or equivalent

ICPI, immune checkpoint inhibitors; ADL, activities of daily living; ULN, upper limit of normal; PO, per os; i.v., intravenous.