Avelumab

Adrenal insufficiency may occur. The median time to onset was 2.5 months (range: 1 day to 8 months). In clinical studies, all patients received corticosteroid therapy for adrenal insufficiency; in patients who received high-dose corticosteroids, the median duration of high-dose systemic corticosteroid therapy was 1 day (range: 1 day to 24 days). Monitor for signs/symptoms of adrenal insufficiency both during and after treatment. Administer corticosteroids as appropriate. Withhold avelumab for severe (grade 3) or life-threatening (grade 4) toxicity.

Type 1 diabetes mellitus has occurred (including diabetic ketoacidosis). Monitor closely for hyperglycemia and other signs/symptoms of diabetes. Insulin or other anti-hyperglycemic therapy may be required; if severe hyperglycemia is observed, administer antihyperglycemics or insulin and withhold avelumab treatment until glucose control has been accomplished.

Immune-mediated colitis has occurred. The median time to onset of colitis was 2.1 months (range: 2 days to 11 months) and the median duration was 6 weeks (range: 1 day to over 14 months). In many patients, colitis was managed with high-dose systemic corticosteroids for a median duration of 19 days (range: 1 day to 2.3 months), followed by a corticosteroid taper. More than two-thirds of patients with colitis experienced resolution. May require treatment interruption, systemic corticosteroid therapy, and/or permanent discontinuation. Monitor for signs and symptoms of colitis; administer systemic corticosteroids (prednisone initial dose of 1 to 2 mg/kg/day [or equivalent] followed by a taper) for grade 2 or higher colitis.

Immune-mediated hepatitis has occurred, including fatal cases. The median onset for hepatitis was 3.2 months (range: 7 days to 15 months); the median duration was 2.5 months (range: 1 day to over 7 months). Hepatitis resolved in approximately half of the patients. Administer corticosteroids (prednisone initial dose of 1 to 2 mg/kg/day [or equivalent] followed by a taper for grade 2 or higher hepatitis), and withhold or discontinue therapy based on the severity of liver enzyme elevations. Systemic corticosteroids were used to manage immune-mediated hepatitis; the median duration of high-dose corticosteroid therapy was 14 days (range: 1 day to 2.5 months). Monitor for liver function changes. May require treatment interruption, systemic corticosteroids (for grade 2 or higher toxicity), and/or permanent discontinuation.

Infusion-related reactions (including severe and life-threatening cases) have occurred. Prior to the initial four infusions, premedicate with an antihistamine and acetaminophen. Monitor for signs/symptoms of a reaction (eg, pyrexia, chills, wheezing, flushing, hypotension, dyspnea, back pain, abdominal pain, urticaria). Some infusion-related reactions occurred after completion of the infusion. Interrupt or slow the rate of infusion for mild or moderate infusion-related reactions. Stop infusion and permanently discontinue for severe (grade 3) or life-threatening (grade 4) infusion-related reactions.

Immune-mediated nephritis has occurred. Grade 2 or higher nephritis should be managed with systemic corticosteroids (prednisone initial dose of 1 to 2 mg/kg/day [or equivalent], followed by a taper). Monitor serum creatinine at baseline and periodically during therapy. May require treatment interruption, systemic corticosteroids (for grade 2 or higher toxicity), and/or permanent discontinuation.

Immune-mediated pneumonitis has been observed, including fatal cases. The median time to development was 2.5 months (range: 3 days to 11 months) and the median duration was 7 weeks (range: 4 days to over 4 months). Pneumonitis was managed with systemic corticosteroids; the median duration of initial corticosteroid therapy was 8 days (range: 1 day to 2.3 months) followed by a corticosteroid taper. Pneumonitis resolved in approximately half of the affected patients. May require treatment interruption, corticosteroid therapy (prednisone initial dose of 1 to 2 mg/kg /day [or equivalent] followed by a taper, for grade 2 or higher pneumonitis), and/or permanent discontinuation. Monitor for signs and symptoms of pneumonitis; if pneumonitis is suspected, evaluate with radiographic imaging; administer systemic corticosteroids for grade 2 or higher pneumonitis.

Immune-mediated hyperthyroidism, hypothyroidism, and thyroiditis have occurred; and may develop at any time during avelumab treatment. The median onset for immune-mediated thyroid disorders was 2.8 months (range: 2 weeks to 13 months). Monitor for changes in thyroid function (at baseline, periodically during treatment, and as clinically indicated) and for signs/symptoms of thyroid disorders. Administer medical management for hyperthyroidism as appropriate; may require treatment interruption and/or permanent discontinuation. Manage hypothyroidism with replacement therapy. Immune-mediated thyroid disorders may require treatment interruption.

Other clinically relevant immune-mediated disorders have been observed rarely with avelumab use and may affect any organ system (may be fatal), including myocarditis, myositis, psoriasis, arthritis, exfoliative dermatitis, erythema multiforme, pemphigoid, hypopituitarism, uveitis, Guillain-Barré syndrome, and systemic inflammatory response. May occur during treatment or following discontinuation. Other immune-mediated disorders have been observed with other similar medications (same class), including bullous dermatitis, Stevens Johnson syndrome/toxic epidermal necrolysis, pancreatitis, rhabdomyolysis, myasthenia gravis, histiocytic necrotizing lymphadenitis, demyelination, vasculitis, hemolytic anemia, hypophysitis, iritis, and encephalitis. If an immune-mediated adverse event is suspected, evaluate appropriately to confirm or exclude other causes; based on severity of reaction, withhold treatment and administer systemic corticosteroids and (if appropriate) hormone replacement therapy. Upon resolution to grade 0 or 1, initiate corticosteroid taper. When reaction remains at grade 1 or less during taper may reinitiate avelumab. Discontinue permanently for severe grade 3 immune-mediated adverse event that is recurrent and for life-threatening reactions. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.