jemperli

Important safety information

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune‑mediated pneumonitis, immune-mediated colitis, immune‑mediated hepatitis, immune-mediated endocrinopathies, immune-mediated nephritis with renal dysfunction, immune‑mediated dermatologic adverse reactions, and solid organ transplant rejection. Monitor for signs and symptoms of immune‑mediated adverse reactions. Evaluate clinical chemistries, including liver enzymes, creatinine, and thyroid function, at baseline and periodically during treatment. Withhold or permanently discontinue JEMPERLI and administer corticosteroids based on the severity of reaction. ( 2.3 , 5.1 ) • Infusion-related reactions: Interrupt, slow the rate of infusion, or permanently discontinue JEMPERLI based on severity of reaction. ( 2.3 , 5.2 ) • Complications of allogeneic hematopoietic stem cell transplantation (HSCT): Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD‑1/PD-L1–blocking antibody. ( 5.3 ) • Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.4 , 8.1 , 8.3 ) 5.1 Severe and Fatal Immune-Mediated Adverse Reactions JEMPERLI is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance, and inducing immune-mediated adverse reactions. Important immune-mediated adverse reactions listed in WARNINGS AND PRECAUTIONS may not include all possible severe and fatal immune‑mediated reactions. Immune-mediated adverse reactions, which can be severe or fatal, can occur in any organ system or tissue. Immune‑mediated adverse reactions can occur at any time after starting a PD-1/PD-L1–blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1–blocking antibodies, they can also manifest after discontinuation of PD-1/PD-L1–blocking antibodies. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD‑1/PD‑L1–blocking antibodies. Monitor closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function tests at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue JEMPERLI depending on severity [see Dosage and Administration ( 2.3 )] . In general, if JEMPERLI requires interruption or discontinuation, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reaction is not controlled with corticosteroids. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies, dermatologic reactions) are discussed below. Immune-Mediated Pneumonitis JEMPERLI can cause immune-mediated pneumonitis, which can be fatal. In patients treated with other PD-1/PD-L1–blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 2.3% (14/605) of patients receiving JEMPERLI, including Grade 2 (1.3%), Grade 3 (0.8%) and Grade 4 (0.2%) pneumonitis. Pneumonitis led to discontinuation of JEMPERLI in 1.3% of patients. Systemic corticosteroids were required in 79% (11/14) of patients with pneumonitis. Pneumonitis resolved in 11 of the 14 patients. JEMPERLI was withheld for 9 patients. Five patients reinitiated JEMPERLI after symptom improvement; of these, 2 patients had recurrence of pneumonitis. Immune-Mediated Colitis 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 1.3% (8/605) of patients receiving JEMPERLI, including Grade 2 (0.7%) and Grade 3 (0.7%) adverse reactions. Colitis led to discontinuation of JEMPERLI in 1 (0.2%) patient. Systemic corticosteroids were required in 75% (6/8) of patients with colitis. Colitis resolved in 5 of the 8 patients. Of the 4 patients in whom JEMPERLI was withheld for colitis, all reinitiated treatment with JEMPERLI; of these, 1 patient had recurrence of colitis. Immune-Mediated Hepatitis JEMPERLI can cause immune-mediated hepatitis, which can be fatal. Immune-mediated hepatitis occurred in 0.5% (3/605) of patients receiving JEMPERLI, all were Grade 3. Hepatitis led to discontinuation of JEMPERLI in 1 (0.2%) patient. Systemic corticosteroids were required in 2 patients with hepatitis and the events resolved in 2 of the 3 patients. 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 or permanently discontinue JEMPERLI depending on severity [see Dosage and Administration ( 2.3 )] . Adrenal insufficiency occurred in 1.2% (7/605) patients receiving JEMPERLI, including Grade 2 (0.5%) and Grade 3 (0.7%). Adrenal insufficiency resulted in discontinuation in 1 (0.2%) patient and resolved in 4 of the 7 patients. Of the 4 patients in whom JEMPERLI was withheld for adrenal insufficiency, all reinitiated treatment with JEMPERLI. Systemic corticosteroids were required in 5 of the 7 patients with adrenal insufficiency. 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 or permanently discontinue JEMPERLI depending on severity [see Dosage and Administration ( 2.3 )] . JEMPERLI in Combination with Carboplatin and Paclitaxel: Hypophysitis (Grade 3) occurred in 0.4% (1/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Systemic corticosteroids were required, and the event resolved. JEMPERLI was withheld and the patient reinitiated treatment. JEMPERLI as a Single Agent: Hypophysitis (Grade 2) occurred in 0.2% (1/605) of patients receiving JEMPERLI as a single agent. Systemic corticosteroids were required, and the event did not resolve. JEMPERLI was withheld and the patient reinitiated treatment. Thyroid Disorders: JEMPERLI can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate thyroid hormone replacement or medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity [see Dosage and Administration ( 2.3 )] . Thyroiditis: Thyroiditis occurred in 0.5% (3/605) of patients receiving JEMPERLI; all were Grade 2. Systemic corticosteroids were required in 1 of 3 patients and anti-thyroid therapy was required for 2 of 3 patients with thyroiditis. JEMPERLI was withheld for 1 patient and the patient reinitiated treatment. None of…