Grade 3 diarrhoea or colitis OPDIVO+ipilimumab Permanently discontinue treatment Grade 4 diarrhoea or colitis Permanently discontinue treatment Immunerelated hepatitis Grade 2 elevation in aspartate Withhold dose(s) until laboratory values aminotransferase (AST), alanine return to baseline and management with aminotransferase (ALT), or total bilirubin corticosteroids, if needed, is complete Grade 3 or 4 elevation in AST, ALT, or Permanently discontinue treatment total bilirubin Immunerelated nephritis Grade 2 or 3 creatinine elevation Withhold dose(s) until creatinine returns and renal dysfunction to baseline and management with corticosteroids is complete Grade 4 creatinine elevation Permanently discontinue treatment Symptomatic Grade 2 or 3 Withhold dose(s) until symptoms resolve hypothyroidism, hyperthyroidism, and management with corticosteroids (if hypophysitis needed for symptoms of acute inflammation) is complete. OPDIVO Grade 2 adrenal insufficiency should be continued in the presence of 3 diabetes hormone replacement therapya as long as no symptoms are present Immunerelated endocrinopathies Grade 4 hypothyroidism Grade 4 hyperthyroidism Permanently discontinue treatment Grade 4 hypophysitis 3 or 4 adrenal insufficiency Grade 4 diabetes Grade 3 rash Withhold dose(s) until symptoms resolve and management with corticosteroids is Immune-related rash and complete severe skin reactions Permanently discontinue treatment Grade 4 rash New onset moderate or severe neurologic Withhold dose(s) until symptoms resolve signs or symptoms and management with corticosteroids is Encephalitis complete Permanently discontinue treatment Immune-related encephalitis Other adverse reactions Other Grade 3 adverse reaction Withhold dose(s) until symptoms resolve First occurrence and management with corticosteroids is complete Recurrence of same Grade 3 adverse Permanently discontinue reactions Life-threatening or Grade 4 adverse reaction Inability to reduce corticosteroid dose to 10 mg prednisone or equivalent per day
Grade 3 diarrhoea or colitis OPDIVO+ipilimumab Permanently discontinue treatment Grade 4 diarrhoea or colitis Permanently discontinue treatment Immunerelated hepatitis Grade 2 elevation in aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin Withhold dose(s) until laboratory values return to baseline and management with corticosteroids, if needed, is complete Grade 3 or 4 elevation in AST, ALT, or total bilirubin Permanently discontinue treatment Immunerelated nephritis and renal dysfunction Grade 2 or 3 creatinine elevation Withhold dose(s) until creatinine returns to baseline and management with corticosteroids is complete Grade 4 creatinine elevation Permanently discontinue treatment Immunerelated endocrinopathies Symptomatic Grade 2 or 3 hypothyroidism, hyperthyroidism, hypophysitis Grade 2 adrenal insufficiency 3 diabetes Grade 4 hypothyroidism Grade 4 hyperthyroidism Grade 4 hypophysitis 3 or 4 adrenal insufficiency Grade 4 diabetes Withhold dose(s) until symptoms resolve and management with corticosteroids (if needed for symptoms of acute inflammation) is complete. OPDIVO should be continued in the presence of hormone replacement therapya as long as no symptoms are present Permanently discontinue treatment Immune-related rash and severe skin reactions Grade 3 rash Grade 4 rash Withhold dose(s) until symptoms resolve and management with corticosteroids is complete Permanently discontinue treatment Encephalitis New onset moderate or severe neurologic signs or symptoms Immune-related encephalitis Withhold dose(s) until symptoms resolve and management with corticosteroids is complete Permanently discontinue treatment Other adverse reactions Other Grade 3 adverse reaction First occurrence Withhold dose(s) until symptoms resolve and management with corticosteroids is complete Recurrence of same Grade 3 adverse reactions Permanently discontinue Life-threatening or Grade 4 adverse reaction Inability to reduce corticosteroid dose to 10 mg prednisone or equivalent per day
auspar-nivolumab-160823-pi.docx