Tislelizumab: Drug information

For additional information see "Tislelizumab: Patient drug information"

For abbreviations, symbols, and age group definitions show table

Pharmacologic Category

Antineoplastic Agent, Anti-PD-1 Monoclonal Antibody;
Antineoplastic Agent, Immune Checkpoint Inhibitor;
Antineoplastic Agent, Monoclonal Antibody

Dosing: Adult

Esophageal squamous cell carcinoma, unresectable or metastatic

Esophageal squamous cell carcinoma, unresectable or metastatic: IV: 200 mg once every 3 weeks; continue until disease progression or unacceptable toxicity (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Kidney impairment prior to treatment initiation:

Note: Kidney function estimated using Cockcroft-Gault equation.

CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling; however, there are no clinically significant differences in tislelizumab pharmacokinetics.

CrCl 15 to 29 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (effect on tislelizumab pharmacokinetics is unknown).

End-stage kidney disease (CrCl <15 mL/minute): There are no dosage adjustments provided in the manufacturer’s labeling (effect on tislelizumab pharmacokinetics is unknown).

Kidney toxicity during treatment:

Note: If tislelizumab treatment interruption or discontinuation is required, administer systemic corticosteroids (prednisone 1 to 2 mg/kg/day [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions until improvement to grade 1 or lower, then follow with a corticosteroid taper and continue to taper over at least 1 month. Prednisone tapering recommendations when used for immune-mediated adverse reactions associated with immune checkpoint inhibitor therapy may be found in the Prednisone monograph.

Immune-mediated nephritis with kidney dysfunction:

Grade 2 or grade 3 serum creatinine elevation: Withhold tislelizumab; resume tislelizumab after complete or partial (to grade 0 or 1) resolution after corticosteroid taper. Permanently discontinue tislelizumab if no complete or partial resolution within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.

Grade 4 serum creatinine elevation: Permanently discontinue tislelizumab.

Dosing: Hepatic Impairment: Adult

Hepatic impairment prior to treatment initiation:

Mild to moderate impairment (total bilirubin ≤3 times ULN and any AST): There are no dosage adjustments provided in the manufacturer’s labeling; however, there are no clinically significant differences in tislelizumab pharmacokinetics.

Severe impairment (total bilirubin >3 times ULN and any AST): There are no dosage adjustments provided in the manufacturer’s labeling (effect on tislelizumab pharmacokinetics is unknown).

Acute hepatotoxicity during treatment:

Note: If tislelizumab treatment interruption or discontinuation is required, administer systemic corticosteroids (prednisone 1 to 2 mg/kg/day [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions until improvement to grade 1 or lower, then follow with a corticosteroid taper and continue to taper over at least 1 month. Prednisone tapering recommendations when used for immune-mediated adverse reactions associated with immune checkpoint inhibitor therapy may be found in the Prednisone monograph.

Immune-mediated hepatitis without tumor involvement of the liver:

AST or ALT >3 up to 8 times ULN or total bilirubin >1.5 up to 3 times ULN: Withhold tislelizumab treatment. Resume tislelizumab treatment after complete or partial resolution (to grade 0 or 1) of hepatitis after corticosteroid taper. Permanently discontinue tislelizumab if no complete or partial resolution within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.

AST or ALT >8 times ULN or total bilirubin >3 times ULN: Permanently discontinue tislelizumab.

Immune-mediated hepatitis with tumor involvement of the liver: Note: If AST and ALT are ≤ ULN at baseline, follow recommendations for hepatitis without tumor involvement of the liver.

If baseline AST or ALT >1 up to 3 times ULN and increases to >5 up to 10 times ULN or baseline AST or ALT >3 up to 5 times ULN and increases to >8 up to 10 times ULN: Withhold tislelizumab treatment. Resume tislelizumab treatment with complete or partial resolution (to grade 0 or 1) of hepatitis after corticosteroid taper. Permanently discontinue tislelizumab if no complete or partial resolution within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.

AST or ALT increases to >10 times ULN or total bilirubin increases to >3 times ULN: Permanently discontinue tislelizumab.

Addit ional recommendations:

Grade 2 immune-mediated hepatitis: Withhold immune checkpoint inhibitor (ICI); if no improvement within 3 to 5 days after ICI is withheld, consider initiation of corticosteroids (prednisone 0.5 to 1 mg/kg/day or equivalent) (Ref).

Grade 3 or 4 immune-mediated hepatitis: Withhold ICI; initiate corticosteroids (methylprednisolone 1 to 2 mg/kg or equivalent) (Ref). Based on data from a retrospective cohort study in patients with grade 3 or 4 immune-mediated hepatitis, initial treatment with methylprednisolone 1 mg/kg/day demonstrated similar time to ALT normalization (compared with higher methylprednisolone doses), while reducing the potential for corticosteroid-related complications (Ref).

Dosing: Obesity: Adult

American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m²: The dosing in the approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m²experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status (Ref).

Dosing: Adjustment for Toxicity: Adult

Note: No dosage reductions of tislelizumab are recommended.

Immune-mediated adverse reactions (general information): In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies (eg, infection). Institute medical management promptly, including specialty consultation when appropriate. Withhold tislelizumab for severe (grade 3) immune-mediated adverse reactions. Permanently discontinue tislelizumab for life-threatening (grade 4) immune-mediated adverse reactions, recurrent severe (grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or inability to reduce corticosteroid dose to prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating corticosteroids. If tislelizumab treatment interruption or discontinuation is required, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) until improvement to ≤ grade 1; upon improvement to ≤ grade 1, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants if immune-mediated adverse reaction is not controlled with corticosteroid therapy. Systemic corticosteroids may not be necessary for certain adverse reactions. Hormone-replacement therapy may be required for endocrinopathies (if clinically indicated). See table for additional dosage modification guidance.

Additional management recommendations: Consider withholding checkpoint inhibitor therapy for most grade 2 toxicities and resume when symptoms and/or lab values resolve to ≤ grade 1; systemic corticosteroids (initial dose of 0.5 to 1 mg/kg/day prednisone [or equivalent]) may be administered if indicated for grade 2 toxicities (Ref). Refer to guideline for further information regarding management of immune-mediated adverse reactions associated with immune checkpoint inhibitor therapy.

**Tislelizumab Recommended Dosage Modifications for Adverse Reactions^a**
Adverse reaction	Severity	Tislelizumab dosage modification
^a SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; DRESS = drug rash with eosinophilia and systemic symptoms.
^b Prednisone tapering recommendations when used for immune-mediated adverse reactions associated with immune checkpoint inhibitor therapy may be found in the Prednisone monograph.
Immune-mediated adverse reactions
Cardiovascular toxicity: myocarditis	Grade 2, 3, or 4	Permanently discontinue tislelizumab.
Dermatologic toxicity	Mild or moderate nonexfoliative rash	May be managed with topical emollients and/or topical corticosteroids.
	Exfoliative dermatologic conditions: grade 3 or suspected SJS, TEN, or DRESS	Withhold tislelizumab; resume tislelizumab after complete or partial (to grade 0 or 1) resolution after corticosteroid taper.^b Permanently discontinue tislelizumab if no complete or partial resolution within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
	Grade 4 or confirmed SJS, TEN, or DRESS	Permanently discontinue tislelizumab.
Endocrinopathies	Grade 3 or 4	Withhold tislelizumab until clinically stable or permanently discontinue depending on severity.
	Adrenal insufficiency, ≥ grade 2	Withhold tislelizumab (depending on the severity). Initiate symptomatic management (including hormone replacement as clinically indicated).
	Diabetes, type 1	Withhold or permanently discontinue tislelizumab (depending on the severity). Initiate insulin therapy as clinically indicated.
	Hypophysitis	Withhold or discontinue tislelizumab (depending on the severity). Initiate hormone-replacement therapy as clinically indicated.
	Hyperthyroidism/Thyroiditis	Withhold or discontinue tislelizumab (depending on the severity). Initiate medical management as clinically indicated.
	Hypothyroidism	Withhold tislelizumab (depending on the severity). Initiate thyroid hormone-replacement therapy as clinically indicated.
GI toxicity: colitis	Grade 2 or 3	Withhold tislelizumab; resume tislelizumab after complete or partial (to grade 0 or 1) resolution after corticosteroid taper.^b Permanently discontinue tislelizumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
GI toxicity: colitis	Grade 4	Permanently discontinue tislelizumab.
Ocular disorders: Vogt-Koyanagi-Harada-like syndrome		May require systemic corticosteroids to reduce the risk of permanent vision loss.
Pulmonary toxicity: pneumonitis	Grade 2	Withhold tislelizumab; resume tislelizumab after complete or partial (to grade 0 or 1) resolution after corticosteroid taper.^b Permanently discontinue tislelizumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
Pulmonary toxicity: pneumonitis	Recurrent grade 2, 3, or 4	Permanently discontinue tislelizumab.
Other adverse reactions
Infusion-related reactions	Grade 1	Slow tislelizumab infusion rate by 50%.
	Grade 2	Interrupt tislelizumab infusion; resume tislelizumab infusion at 50% of the previous rate if resolved or decreased to grade 1.
	Grade 3 or 4	Stop infusion and permanently discontinue tislelizumab.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.

>10%:

Dermatologic: Skin rash (13%)

Endocrine & metabolic: Decreased serum albumin (33%), decreased serum phosphate (15%), decreased serum potassium (13%), decreased serum sodium (34%), hypothyroidism (13%), increased serum glucose (46%), weight loss (23%)

Gastrointestinal: Abdominal pain (11%), constipation (15%), decreased appetite (16%), diarrhea (13%; grades 3/4: 1%), dysphagia (11%), nausea (14%; grades 3/4: <1%), vomiting (11%; grades 3/4: <1%)

Hematologic & oncologic: Anemia (31%; grades 3/4: 6%), decreased platelet count (11%; grades 3/4: 1%), hemorrhage (12%; grades 3/4: 2%), lymphocytopenia (43%; grades 3/4: 11%)

Hepatic: Increased serum alanine aminotransferase (23%), increased serum alkaline phosphatase (32%), increased serum aspartate aminotransferase (27%), increased serum bilirubin (11%)

Immunologic: Antibody development (15%; neutralizing: 3%)

Nervous system: Fatigue (28%)

Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (13%), musculoskeletal pain (24%)

Respiratory: Cough (22%), pneumonia (16%)

Miscellaneous: Fever (16%)

1% to 10%:

Endocrine & metabolic: Decreased serum glucose (10%)

Gastrointestinal: Esophageal obstruction (serious: ≥2%)

Hematologic & oncologic: Decreased white blood cell count (10%; grades 3/4: <1%)

Respiratory: Pneumonitis (serious: ≥2%)

Frequency not defined:

Cardiovascular: Myocarditis, pericarditis

Dermatologic: Dermatologic disorder

Endocrine & metabolic: Adrenocortical insufficiency, hyperthyroidism, hypophysitis, pituitary insufficiency, thyroiditis

Gastrointestinal: Colitis

Hepatic: Hepatitis

Hypersensitivity: Infusion-related reaction

Neuromuscular & skeletal: Arthritis, myositis, polymyalgia rheumatica

Renal: Nephritis (with renal dysfunction)

Postmarketing: Dermatologic: Exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Warnings/Precautions

Concerns related to adverse effects:

• Adverse reactions (immune-mediated): PD-1/PD-L1 blockers (including tislelizumab) remove immune response inhibition, thus potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Severe and fatal immune-mediated adverse reactions may occur in any organ system or tissue. Reactions generally occur during treatment (may occur at any time after tislelizumab initiation); reactions may also occur after tislelizumab discontinuation. Early identification and management of immune-mediated adverse reactions are necessary to ensure safe use of tislelizumab. If suspected immune-mediated reactions occur, initiate appropriate workup to exclude alternative causes (including infection).

• Dermatologic toxicity: Tislelizumab may cause immune-mediated rash or dermatitis. Severe cutaneous adverse reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms, have occurred with anti-PD-L1/PD-1 monoclonal antibodies; some cases were fatal. Systemic corticosteroids were required in most patients with immune-mediated dermatologic adverse reactions treated with tislelizumab. Dermatologic adverse reactions led to treatment interruption or permanent discontinuation in a small percentage of patients. Immune-mediated dermatologic adverse reactions resolved in approximately one-half of patients, although one-quarter of patients experienced recurrence of dermatologic toxicity upon reinitiation of tislelizumab.

• Endocrinopathies: Tislelizumab is associated with immune-mediated endocrinopathies (which can be fatal).

– Adrenal insufficiency: Tislelizumab may cause adrenal insufficiency; grades 2, 3, and 4 events have been reported. Adrenal insufficiency did not lead to permanent treatment discontinuation. Treatment interruption and systemic corticosteroids were required in most patients with adrenal insufficiency; adrenal insufficiency resolved in less than one-fifth of patients.

– Diabetes mellitus: Type 1 diabetes mellitus has been reported with PD-1 and PD-L1 blocking antibodies (such as tislelizumab).

– Hypophysitis: Tislelizumab may rarely cause immune-mediated hypophysitis. Hypophysitis may present with acute mass effect–associated symptoms such as headache, photophobia, or visual field defects.

– Thyroid disorders: Tislelizumab may cause immune-mediated thyroid disorders. Hyperthyroidism occurred in a small percentage of patients, including rare grade 2 and 3 events. Discontinuation and treatment interruption were required in only a small number of patients. Systemic corticosteroids were sometimes required. Hyperthyroidism resolved in a majority of patients. Hypothyroidism has also occurred, including grades 2 to 4 events. Hypothyroidism may follow hyperthyroidism. Discontinuation due to hypothyroidism was not required, although treatment interruption was required in a small number of patients. Systemic corticosteroids were required in a small percentage of patients with hypothyroidism; all patients required hormone-replacement therapy, with the majority requiring long-term thyroid hormone replacement. Hypothyroidism resolved in approximately one-fourth of patients. Thyroiditis occurred rarely, including grade 2 events; systemic corticosteroids and treatment interruption were rarely necessary for thyroiditis, and thyroiditis resolved in approximately one-fourth of cases. Thyroiditis can present with or without endocrinopathy.

• GI adverse reactions: Tislelizumab may cause immune-mediated colitis, including fatal events. Immune-mediated colitis occurred in a small percentage of patients, including grade 2 and 3 events. Colitis led to permanent discontinuation or treatment interruption in a small number of patients. Systemic corticosteroids were required in all patients with colitis; some patients required alternative immunosuppressive therapy. Colitis resolved in most patients. Some patients requiring treatment interruption for colitis reinitiated tislelizumab, and colitis recurred in a small number of these patients. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis who received anti-PD-L1/PD-1 monoclonal antibodies. Pancreatitis (including increased serum amylase and lipase levels), gastritis, and duodenitis have also been reported.

• Hepatitis: Tislelizumab may cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in a small percentage of patients, including grade 2 and higher events (some fatal). Hepatitis led to permanent discontinuation or treatment interruption in a small percentage of patients. Systemic corticosteroids were required in all patients with hepatitis; some patients required high-dose systemic corticosteroids or additional immunosuppression. Hepatitis resolved in over one-half of patients. Recurrence was observed in less than one-fifth of patients who reinitiated tislelizumab (following symptom improvement).

• Infusion-related reactions: Severe or life-threatening infusion-related reactions have occurred (rarely) in patients receiving tislelizumab.

• Kidney toxicity: Tislelizumab may cause immune-mediated nephritis with kidney dysfunction, including fatalities. Grade 2, 3, and 4 events have occurred in a small number of patients. Nephritis led to treatment interruption or permanent discontinuation rarely. Systemic corticosteroids were required in all patients with nephritis. Nephritis resolved in over half of patients. Some patients requiring treatment interruption for nephritis reinitiated tislelizumab after symptom improvement and rarely experienced recurrence.

• Ocular disorders: Ocular events, including uveitis, iritis, and other ocular inflammatory toxicities have been reported; some cases may be associated with retinal detachment. Various grades of visual impairment (including blindness) may occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome.

• Pneumonitis: Tislelizumab may cause immune-mediated pneumonitis, which may be fatal. In patients who received other anti-PD-L1/PD-1 monoclonal antibodies, the incidence of pneumonitis was higher in patients who received prior thoracic radiation. Grade 2 to 4 events have been observed. Pneumonitis led to permanent discontinuation or treatment interruption in a small percentage of patients. Systemic corticosteroids were required in all patients with pneumonitis. Pneumonitis resolved in approximately one-half of patients. Of the patients who reinitiated tislelizumab (following symptom improvement), some experienced recurrence of pneumonitis.

• Other immune-mediated toxicities: Other clinically significant immune-mediated adverse reactions have been reported rarely with tislelizumab or with other anti-PD-L1/PD-1 monoclonal antibodies (some have been severe or fatal). Events have included meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy, myocarditis, pericarditis, vasculitis, myositis/polymyositis, rhabdomyolysis (and associated sequelae including renal failure), arthritis, polymyalgia rheumatica, hypoparathyroidism, hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia (formerly known as immune thrombocytopenic purpura), solid organ transplant rejection, and other transplant (including corneal graft) rejection.

Disease-related concerns:

• Hematopoietic cell transplant: Fatal and other serious complications may occur in patients who receive allogeneic hematopoietic cell transplant (HCT) before or after treatment with an anti-PD-L1/PD-1 monoclonal antibody. Transplant-related complications included hyperacute graft-versus-host disease (GVHD), acute or chronic GVHD, hepatic veno-occlusive disease (also known as sinusoidal obstruction syndrome) after reduced-intensity conditioning, and steroid-requiring febrile syndrome (with no identified infectious etiology). These complications may occur despite intervening therapy between PD-L1/PD-1 blockade and HCT. Manage early signs/symptoms of transplant-related complications promptly. Assess the risks/benefits of treatment with an anti-PD-L1/PD-1 monoclonal antibody prior to or after an allogenic HCT.

• Myasthenia gravis: Checkpoint inhibitors may worsen or precipitate new myasthenia gravis (MG), especially within the first 16 weeks of treatment; use with caution. Patients with well-controlled MG may be considered for checkpoint inhibitor therapy if MG treatment is maintained (or reinitiated in patients whose MG is in remission), combination therapy (eg, anti-CTLA-4 with anti-PD-a/PD-L1 monoclonal antibodies) is avoided, and respiratory and bulbar function are closely followed. In patients who develop overt MG during checkpoint inhibitor therapy, early aggressive treatment with plasma exchange or IVIG in combination with high-dose corticosteroids may be required (AAN [Narayanaswami 2021]).

Product Availability

Tevimbra: FDA approved March 2024; availability anticipated in 2^nd half of 2024.

Administration: Adult

IV: Infuse the initial dose over 60 minutes; if tolerated, may infuse subsequent doses over 30 minutes. Infuse through an IV line with a sterile, nonpyrogenic, low-protein binding, 0.2 or 0.22 micron inline or add-on filter. Do not infuse other medications through the same IV line. Do not administer as IV push or bolus. Flush IV line following completion of the infusion.

Interrupt or slow the infusion for grade 1 or grade 2 infusion-related reactions; permanently discontinue tislelizumab for grade 3 or 4 infusion-related reactions.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Tevimbra: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761232Orig1s000lbl.pdf#page=19

Use: Labeled Indications

Esophageal squamous cell carcinoma, unresectable or metastatic: Treatment of unresectable or metastatic esophageal squamous cell carcinoma in adults after prior systemic chemotherapy that did not include a PD-1/PD-L1 inhibitor.

Medication Safety Issues

Sound-alike/look-alike issues:

Tislelizumab may be confused with atezolizumab, pembrolizumab, tafasitamab, tisotumab vedotin, teplizumab, tezepelumab, tocilizumab, toripalimab, tremelimumab.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Acetaminophen: May diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy

Antibiotics: May diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy

Corticosteroids (Systemic): May diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Management: Carefully consider the need for corticosteroids, at doses of a prednisone-equivalent of 10 mg or more per day, during the initiation of immune checkpoint inhibitor therapy. Use of corticosteroids to treat immune related adverse events is still recommended Risk D: Consider therapy modification

Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Inhibitors of the Proton Pump (PPIs and PCABs): May diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy

Ketoconazole (Systemic): Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies) may enhance the hepatotoxic effect of Ketoconazole (Systemic). Risk C: Monitor therapy

Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Reproductive Considerations

Verify pregnancy status prior to treatment initiation in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy and for 4 months after the last tislelizumab dose.

Pregnancy Considerations

Tislelizumab is Fc-engineered humanized monoclonal antibody (IgG₄) that may cross the placenta. Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).

Based on the mechanism of action, in utero exposure to tislelizumab may disrupt maternal tolerance to the fetus, increasing the risk of abortion or stillbirth. Based on animal data, maternal use of a PD-1/PD-L1 inhibitor may also result in immune-mediated disorders in the newborn.

The European Society for Medical Oncology (ESMO) has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team) approach (ESMO [Peccatori 2013]).

A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (877-635-4499).

Breastfeeding Considerations

It is not known if tislelizumab is present in breast milk.

Tislelizumab is Fc-engineered humanized monoclonal antibody (IgG₄). Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Anderson 2021).

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 4 months after the last tislelizumab dose.

Monitoring Parameters

Monitor hepatic function (AST, ALT, and total bilirubin; at baseline and periodically during treatment); kidney function (serum creatinine; at baseline and periodically during treatment); thyroid function (at baseline, periodically during treatment and as clinically indicated); monitor blood glucose (for hyperglycemia). Verify pregnancy status (prior to therapy in patients who could become pregnant). Monitor closely for signs/symptoms of immune-mediated adverse reactions, including adrenal insufficiency, diarrhea/colitis (consider initiating or repeating infectious workup in patients with corticosteroid-refractory immune-mediated colitis to exclude alternative causes), dermatologic toxicity, diabetes mellitus, hypophysitis, ocular disorders, thyroid disorders, pneumonitis, and other immune-mediated adverse reactions. Monitor for signs/symptoms of infusion-related reactions. If received/receiving hematopoietic stem cell transplant, monitor closely for early signs/symptoms of transplant-related complications.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]). Obtain baseline ECG, natriuretic peptides, and troponins in all patients; obtain a baseline echocardiogram in high-risk patients; consider serial ECGs and cardiac troponins prior to doses 2, 3, and 4, and if normal, reduce to every 3 doses until completion of therapy; cardiovascular risk assessment every 6 to 12 months in high-risk patients who require long-term (>12 months) therapy, consider cardiovascular risk assessment every 6 to 12 months in all patients requiring long-term therapy (ESC [Lyon 2022]). Refer to a cardiologist when clinically indicated.

Additional suggested monitoring (ASCO [Schneider 2021):

Prior to therapy: CBC with differential, serum chemistries, creatine kinase, comprehensive clinical assessment including performance status, weight, BMI, heart rate, BP, and oxygen saturation; consider chest x-ray, ECG, and CT scan; assess history of autoimmune conditions, organ-specific disease, endocrinopathies, neuropathy, and infectious disease; assess bowel habits, respiratory symptoms, skin (for rash), arthralgias, and neurologic symptoms.

During therapy: Assess BP, weight, heart rate, and oxygen saturation; assess for infections, screen for hyperglycemia/diabetes (polyuria, polydipsia, weight loss); eye exam (including intraocular pressure after 6 weeks), CBC with differential, serum chemistries, and creatine kinase; monitor bone mineral density (with long-term therapy).

Mechanism of Action

Tislelizumab is a recombinant humanized IgG4 kappa monoclonal antibody that inhibits programmed death-1 (PD-1) activity by binding to PD-1 and blocking the interactions with the ligands PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of immune response, including anti-tumor response. PD-1 ligand upregulation may occur in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Blocking PD-1 activity has resulted in decreased tumor growth in animal models.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: V_d: 6.42 L.

Half-life elimination: 24 days.

Excretion: Clearance: 0.153 L/day.

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Tevimbra (tislelizumab) [prescribing information]. San Mateo, CA: BeiGene USA Inc; March 2024.

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Tislelizumab: Drug information