FDA Approves JEMPERLI (dostarlimab-gxly) for dMMR Endometrial Cancer - Seite 4

• JEMPERLI can cause immune-mediated colitis. Cytomegalovirus infection/reactivation have occurred in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1–blocking antibodies. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.
• Immune-mediated colitis occurred in 1.4% (6/444) of patients, including Grade 3 (0.7%) and Grade 2 (0.7%). Colitis did not lead to discontinuation of JEMPERLI in any patients. Systemic corticosteroids were required in 17% (1/6) of patients with colitis. Colitis resolved in 50% of the 6 patients. Of the 2 patients in whom JEMPERLI was withheld for colitis, both reinitiated JEMPERLI.

Immune-Mediated Hepatitis

• JEMPERLI can cause immune-mediated hepatitis, which can be fatal. Immune-mediated Grade 3 hepatitis occurred in 0.2% (1/444) of patients. Systemic corticosteroids were required, and the event resolved.
  

Immune-Mediated Endocrinopathies

• Adrenal Insufficiency
  • JEMPERLI can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment per institutional guidelines, including hormone replacement as clinically indicated. Withhold JEMPERLI if not clinically stable. Adrenal insufficiency occurred in 0.9% (4/444) of patients, including Grade 3 (0.5%) and Grade 2 (0.5%). Adrenal insufficiency resulted in discontinuation in 1 (0.2%) patient and resolved in 25% of the 4 patients.
• Hypophysitis
  • JEMPERLI can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated. Withhold JEMPERLI if not clinically stable.
• Thyroid Disorders
  • JEMPERLI can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement or medical management of hyperthyroidism as clinically indicated. Withhold JEMPERLI if not clinically stable.
  • Thyroiditis occurred in 0.5% (2/444) of patients; both were Grade 2. Neither event of thyroiditis resolved; there were no discontinuations of JEMPERLI due to thyroiditis.
  • Hypothyroidism occurred in 5.6% (25/444) of patients, all of which were Grade 2. Hypothyroidism did not lead to discontinuation of JEMPERLI and resolved in 40% of the 25 patients. Systemic corticosteroids were not required for any of the 25 patients with hypothyroidism.
  • Hyperthyroidism occurred in 1.8% (8/444) of patients, including Grade 2 (1.6%) and Grade 3 (0.2%). Hyperthyroidism did not lead to discontinuation of JEMPERLI and resolved in 63% of the 8 patients. Systemic corticosteroids were not required for any of the 8 patients with hyperthyroidism.
• Type 1 Diabetes Mellitus, Which Can Present with Diabetic Ketoacidosis
  • JEMPERLI can cause type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.