Immune-related adverse reactions and treatment modification protocols

Level 4

Grade 3 to 4 or recurrent grade 2

Grade 4

Grade 3 to 4, AST or ALT > 5 times ULN, or TBIL > 3 times ULN

Nephritis

Dermal adverse reactions

Grade 4, Stevens-Johnson syndrome or toxic epidermolysis bullosa

Grade 4

Infusion reactions

Grade 3 to 4

Immune-related adverse reactions Severity Treatment adjustment
reactive capillary hyperplasia Grade 3 Drug suspension
Permanent discontinuation
Pneumonia Grade 2 Suspension of dosing until adverse reactions return to grade 0 to 1
Permanent discontinuation
Diarrhea and colitis Grade 2 or 3 Suspension of dosing until adverse reactions return to grade 0 to 1
Permanent discontinuation
Hepatitis Grade 2 with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) at 3 to 5 times the upper limit of normal (ULN) or total bilirubin (TBIL) at 1.5 to 3 times the ULN Suspend dosing until adverse reactions return to grade 0 to 1
Permanent discontinuation of medication
Grade 2 to 3 elevated blood creatinine Suspension of dosing until adverse reactions return to grade 0 to 1
Grade 4 blood creatinine elevation Permanent discontinuation
Endocrine disease Symptomatic grade 2 to 3 hypothyroidism, grade 2 to 3 hyperthyroidism, grade 2 to 3 pituitary gland inflammation, grade 2 adrenal insufficiency
Grade 3 hyperglycemia or type 1 diabetes mellitus
Suspend dosing until adverse reactions return to grade 0 to 1
Grade 4 hypothyroidism
Grade 4 hyperthyroidism
Grade 4 pituitary gland inflammation
Grade 3 to 4 adrenal insufficiency
Grade 4 hyperglycemia or type 1 diabetes mellitus
Permanent discontinuation of medication
Grade 3 Suspension of dosing until adverse reactions return to grade 0 to 1
Permanent discontinuation of medication
Thrombocytopenia Grade 3 Suspension of dosing until adverse reactions return to grade 0 to 1
Permanent discontinuation
Other immune-related adverse reactions Grade 3 to 4 elevated blood amylase or elevated lipase
Grade 2 to 3 pancreatitis
Grade 2 myocarditis
Grade 2 to 3 first occurrence of other immune-related adverse reactions
Suspension of dosing until adverse reactions return to grade 0 to 1
Grade 4 pancreatitis or recurrent pancreatitis of any grade
Grade 3 to 4 myocarditis
Grade 3 to 4 encephalitis
Grade 4 first occurrence of other immune-related adverse reactions
Permanent discontinuation
Recurrence or persistent adverse reactions Recurrence grade 3 to 4 (except endocrine disease)
Grade 2 to 3 adverse reactions within 12 weeks of last dose
Not improved to grade 0 to 1 (except endocrine disease)
Failure to reduce glucocorticoids to a prednisone equivalent dose of ≤10 mg/d within 12 weeks of final dosing
Permanent discontinuation
Grade 2 Reduce titration rate or suspend dosing, consider resuming when symptoms resolve and observe closely
Permanent discontinuation of medication