Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use
Traceability

In order to improve the traceability of biological medicinal products, the tradename and the batch number of the administered product should be clearly recorded.

Immune-related adverse reactions

Immune-related adverse reactions, which may be severe or fatal, can occur in patients treated with antibodies blocking the programmed cell death protein-1 / programmed death-ligand 1 (PD-1/PD-L1) pathway, including dostarlimab. While immune-related adverse reactions usually occur during treatment with PD-1/PD-L1 blocking antibodies, symptoms can also manifest after discontinuation of treatment. Immune-related adverse reactions may occur in any organ or tissue and may affect more than one body system simultaneously. Important immune-related adverse reactions listed in this section are not inclusive of all possible severe and fatal immune-related reactions.

Early identification and management of immune-related adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Patients should be monitored for symptoms and signs of immune-related adverse reactions. Haematological and clinical chemistries, including liver, kidney and thyroid function tests, should be evaluated at baseline and periodically during treatment. For suspected immune-related adverse reactions, adequate evaluation including specialty consultation should be ensured.
Based on the severity of the adverse reaction, treatment with dostarlimab should be withheld or permanently discontinued and corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) or other appropriate therapy administered (see below and section 4.2). Upon improvement to grade ≤1, corticosteroid taper should be initiated and continued for 1 month or longer. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Hormone replacement therapy for endocrinopathies should be instituted as warranted.

Treatment with dostarlimab should be permanently discontinued for any grade 3 immune-related adverse reaction that recurs and for any grade 4 immune-related adverse reaction toxicity, except for endocrinopathies that are controlled with replacement hormones and unless otherwise specified in Table 2.

Immune-related pneumonitis
Pneumonitis has been reported in patients receiving dostarlimab (see section 4.8). Patients should be monitored for signs and symptoms of pneumonitis. Suspected pneumonitis should be confirmed with radiographic imaging and other causes excluded. Patients should be managed with dostarlimab treatment modifications and corticosteroids (see section 4.2).

Immune-related colitis
Dostarlimab can cause immune-related colitis (see section 4.8). Patients should be monitored for signs and symptoms of colitis and managed with dostarlimab treatment modifications, anti-diarrhoeal agents and corticosteroids (see section 4.2).

Immune-related hepatitis
Dostarlimab can cause immune-related hepatitis (see section 4.8). Patients should be monitored for changes in liver function periodically as indicated, based on clinical evaluation and managed with dostarlimab treatment modifications and corticosteroids (see section 4.2).

Immune-related endocrinopathies
Immune-related endocrinopathies, including hypothyroidism, hyperthyroidism, thyroiditis, hypophysitis, type 1 diabetes mellitus, diabetic ketoacidosis and adrenal insufficiency, have been reported in patients receiving dostarlimab (see section 4.8).

Hypothyroidism and hyperthyroidism
Immune-related hypothyroidism and hyperthyroidism (including thyroiditis) occurred in patients receiving dostarlimab, and hypothyroidism may follow hyperthyroidism. Patients should be monitored for abnormal thyroid function tests prior to and periodically during treatment and as indicated based on clinical evaluation. Immune-related hypothyroidism and hyperthyroidism (including thyroiditis) should be managed as recommended in section 4.2.

Adrenal insufficiency
Immune-related adrenal insufficiency occurred in patients receiving dostarlimab. Patients should be monitored for clinical signs and symptoms of adrenal insufficiency. For symptomatic adrenal insufficiency, patients should be managed as recommended in section 4.2.

Immune-related nephritis
Dostarlimab can cause immune-related nephritis (see section 4.8). Patients should be monitored for changes in renal function and manage with dostarlimab treatment modifications and corticosteroids (see section 4.2).

Immune-related rash
Immune-related rash has been reported in patients receiving dostarlimab, including pemphigoid (see section 4.8). Patients should be monitored for signs and symptoms of rash. Exfoliative dermatologic conditions should be managed as recommended in section 4.2. Events of Stevens-Johnson Syndrome or toxic epidermal necrolysis have been reported in patients treated with PD-1 inhibitors.
Caution should be used when considering the use of dostarlimab in a patient who has previously experienced a severe or life-threatening skin adverse reaction on prior treatment with other immune-stimulatory anticancer agents.

Immune-related arthralgia
Immune-related arthralgia has been reported in patients receiving dostarlimab (see section 4.8).
Patients should be monitored for signs and symptoms of arthralgia. Suspected immune-related arthralgia should be confirmed and other causes excluded. Patients should be managed with dostarlimab treatment modifications and corticosteroids (see section 4.2).

Other immune-related adverse reactions
Given the mechanism of action of dostarlimab other potential immune-related adverse reactions may occur, including potentially serious events [e.g. myositis, myocarditis, encephalitis, demyelinating neuropathy (including Guillain Barré syndrome), sarcoidosis]. Clinically significant immune-related adverse reactions reported in less than 1 % of patients treated with dostarlimab as monotherapy in clinical studies include encephalitis, autoimmune haemolytic anaemia, pancreatitis, iridocyclitis and uveitis. Patients should be monitored for signs and symptoms of immune-related adverse reactions and managed as described in section 4.2. Solid organ transplant rejection has been reported in the post- marketing setting in patients treated with PD-1 inhibitors. Treatment with dostarlimab may increase the risk of rejection in solid organ transplant recipients. The benefit of treatment with dostarlimab versus the risk of possible organ rejection should be considered in these patients.

Fatal and other serious complications can occur in patients who receive allogeneic haematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1–blocking antibody.
Transplant-related complications include hyperacute graft-versus-host disease (GvHD), acute GvHD, chronic GvHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid- requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1–blocking antibody prior to or after an allogeneic HSCT.

Infusion-related reactions
Dostarlimab can cause infusion-related reactions, which can be severe (see section 4.8). For severe (grade 3) or life-threatening (grade 4) infusion-related reactions, the infusion should be stopped and treatment should be permanently discontinued (see section 4.2).

Patients excluded from clinical studies
Patients with the following status were excluded from the GARNET study: Eastern Cooperative Oncology Group (ECOG) baseline performance score (PS) ≥ 2; uncontrolled central nervous system metastases or carcinomatous meningitis; other malignancies within the last 2 years; immunodeficiency or receiving immunosuppressive therapy within 7 days; active HIV, hepatitis B or hepatitis C infection; active autoimmune disease requiring systemic treatment in the past 2 years excluding replacement therapy; history of interstitial lung disease; or receiving live vaccine within 14 days.

Sodium content

This medicinal product contains less than 1 mmol sodium (23 mg) per 500 mg dose, i.e. essentially 'sodium-free'.

Effects on Driving

4.7    Effects on ability to drive and use machines

JEMPERLI has no or negligible influence on the ability to drive and use machines.