What are the precautions for Tevimbra (Tislelizumab-jsgr)

In the clinical study of Tevimbra (Tislelizumab-jsgr) in the treatment of unresectable or metastatic esophageal squamous cell carcinoma (ESCC) treated with systemic chemotherapy, warnings and precautions such as serious and fatal immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic HSCT, and embryo-fetal toxicity have emerged. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity.

1. Serious and fatal immune-mediated adverse reactions: Tevimbra is a monoclonal antibody, which belongs to a class of drugs that bind programmed death receptor-1 (PD-1) or PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby releasing the suppression of immune responses, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions may be serious or fatal and may occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment with PD-1/PD-L1 blocking antibodies. These include immune-mediated pneumonia, colitis, endocrine diseases, nephritis with renal insufficiency, adverse skin reactions, etc.

Although immune-mediated adverse reactions usually occur during treatment withPD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also occur after discontinuation of PD-1/PD-L1 blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of potential immune-mediated adverse reactions. Liver enzymes, creatinine, and thyroid function were assessed at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate testing to rule out alternative causes, including infection. Establish medical management promptly, including appropriate professional consultation.

2. Infusion-related reactions: can lead to serious or life-threatening infusion-related reactions. Monitor patients for signs and symptoms of infusion-related reactions. For mild (Grade 1) infusion, slow the infusion rate; for moderate (Grade 2) infusion-related reactions, interrupt the infusion. For serious (Grade 3) or life-threatening (Grade 4) infusion-related reactions, discontinue the infusion and permanently discontinue Tevimbra.

3. AllogeneicComplications of HSCT: Patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after receiving PD-1/PD-L1 blocking antibody therapy may develop fatal and other serious complications. Transplantation-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 a clear infectious cause). These complications may occur despite therapeutic intervention between PD-1/PD-L1 blockade and allogeneic HSCT.

Follow patients closely to look for evidence of transplant-related complications and intervene promptly. Consider allogeneicThe pros and cons of using PD-1/PD-L1 blocking antibody therapy before or after HSCT.

4. Embryo-fetal toxicity:

Based on its mechanism of action,Tevimbra can cause harm to the fetus when used by pregnant women. Animal studies have shown that inhibition of the PD-1/PD-L1 pathway can lead to an increased risk of immune-mediated rejection in the developing fetus, leading to fetal death. Inform women of the potential risk to the fetus. Advise females of reproductive potential to use an effective method of contraception during treatment with Tevimbra and for 4 months after the last dose.

Reference: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=08ef1e3e-496f-4b0b-94ee-fbba3cc1985a##