Immune-mediated pneumonitis: Withhold treatment for Grade 2 pneumonitis, & permanently discontinue for Grade 3, Grade 4, or recurrent Grade 2 pneumonitis.
Immune-mediated colitis: Withhold treatment for Grade 2 or 3 colitis, & permanently discontinue for Grade 4 colitis.
Immune-mediated hepatitis (w/o hepatocellular carcinoma): Administer corticosteroids for Grade 2 or greater hepatitis. Withhold if AST or ALT >3 to 5x upper limit of normal (ULN) or total bilirubin >1.5 & up to 3x ULN. Permanently discontinue in patients w/o liver metastases if AST or ALT >5x ULN or total bilirubin >3x ULN. Permanently discontinue in patients w/ liver metastasis & Grade 2 AST or ALT at baseline, w/ an increase in AST or ALT of ≥50% relative to baseline that persists for at least 1 wk. In patients w/ RCC: Withhold both Keytruda & axitinib if ALT or AST ≥3x ULN but <10x ULN w/o concurrent total bilirubin ≥2x ULN, until recovery to Grades 0-1. Consider corticosteroid therapy; or rechallenge w/ a single drug or sequential rechallenge w/ both drugs after recovery. Permanently discontinue both Keytruda & axitinib & consider corticosteroid therapy if ALT or AST ≥10x ULN or >3x ULN w/ concurrent total bilirubin ≥2x ULN.
Immune-mediated endocrinopathies: Withhold treatment for Grade 2 hypophysitis. Withhold or discontinue for Grade 3 or 4 hypophysitis or hyperthyroidism. Administer insulin for type 1 DM, & withhold Keytruda & administer anti-hyperglycemics in patients w/ severe hyperglycemia.
Immune-mediated nephritis & renal dysfunction: Administer corticosteroids for Grade 2 or greater nephritis. Withhold Keytruda for Grade 2, & permanently discontinue for Grade 3 or 4 nephritis.
Immune-mediated skin adverse reactions: Withhold for Grade 3 severe skin reactions or suspected Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). Permanently discontinue for Grade 4 severe skin reactions or confirmed SJS or TEN.
Hematologic toxicity in patient w/ cHL: Withhold treatment for Grade 4 hematologic toxicity until resolution to Grades 0 or 1.
Other immune-mediated adverse reactions: Withhold for any other Grade 2 or 3 treatment-related adverse reaction, based on the severity & type of reaction. Permanently discontinue for Grade 3 (based on severity & type of reaction) or Grade 4 immune-mediated AR; recurrent Grade 2 pneumonitis; recurrent Grade 3 or 4 immune-mediated AR; persistent Grade 2 or 3 AR lasting ≥12 wk after last dose of Keytruda (excluding endocrinopathies controlled w/ hormone replacement therapy).
Infusion-related reactions: Permanently discontinue for Grade 3 or 4 infusion-related reactions. Permanently discontinue if unable to taper corticosteroid dose to <10 mg prednisone or equivalent per day w/in 12 wk after last dose of Keytruda. For the situation of withholding Keytruda, it can be resumed in patients whose AR recover to Grade 1 or less following corticosteroid taper. Closely monitor patients for early evidence of transplant-related complications eg, hyperacute graft versus host disease (GvHD), severe (Grade 3-4) acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, & other immune-mediated AR, & intervene promptly. Risk of GvHD in patients w/ history of allogeneic hematopoietic stem cell transplantation (HSCT). Increased mortality in patients w/ multiple myeloma when Keytruda is combined w/ thalidomide analogue & dexamethasone. Risk of fetal harm. Females of reproductive potential should use effective contraception during treatment & for 4 mth after the last dose. Pregnancy & lactation. Childn.