What are the side effects of tislelizumab and how should they be monitored and managed?

Side Effects of Tislelizumab

Tislelizumab causes grade 3 or higher adverse events in approximately 54% of patients when combined with chemotherapy, with the most common serious effects being hematologic toxicities (decreased neutrophil and platelet counts, anemia, neutropenia) and immune-related adverse events occurring in 31% of patients. 1

Common Adverse Events (All Grades)

Hematologic Toxicities

• Anemia is the most frequently reported adverse event, occurring in 23% of patients 2
• Decreased neutrophil counts and neutropenia are common grade 3-4 events when tislelizumab is combined with chemotherapy 1
• Decreased platelet counts represent another major hematologic toxicity in combination therapy 1
• Thrombocytopenia may occur and requires monitoring 2

Hepatic Toxicities

• Increased aspartate aminotransferase (AST) occurs in 22% of patients 2
• Increased alanine aminotransferase (ALT) is commonly observed 2
• Hepatic injury can be fatal in rare cases 3

Constitutional Symptoms

• Fatigue is one of the most common adverse effects reported 3, 2
• These symptoms are generally grade 1-2 in severity 2

Immune-Related Adverse Events (irAEs)

Incidence and Timing

• 31% of patients experience immune-related adverse events when tislelizumab is combined with chemotherapy, compared to 12% with placebo plus chemotherapy 1
• irAEs typically occur within weeks to 3 months after initiation, though first onset can occur up to 1 year after discontinuation 1

Endocrine irAEs

• Hypothyroidism is one of the most frequently noted immune-mediated adverse events 4
• Endocrine toxicities generally have a median onset of 28.6 weeks (range 19.1-38.1 weeks) for grade 3-4 events 1

Pulmonary irAEs

• Pneumonitis is a frequently reported immune-mediated adverse event requiring vigilant monitoring 4
• Pulmonary toxicities have a median onset of 6.7 weeks for grade 3-4 events 1

Metabolic irAEs

• Hyperglycemia is among the most frequently noted immune-mediated adverse events 4

Dermatologic irAEs

• Skin reactions including rash and pruritus can occur, typically within the first few weeks of treatment 1
• Grade 3-4 skin reactions are rare (<3% with PD-1 monotherapy) 1

Gastrointestinal irAEs

• Colitis can occur as an immune-related adverse event 1
• Gastrointestinal toxicities have a median onset of 26.3 weeks (range 13.1-57.0 weeks) for grade 3-4 events 1

Hepatic irAEs

• Hepatitis may develop as an immune-mediated complication 1
• Hepatic toxicities have a median onset of 7.4 weeks (range 2.1-48.0 weeks) for grade 3-4 events 1

Renal irAEs

• Nephritis is a consideration, particularly in patients with a single kidney 1
• Renal toxicities have a median onset of 50.9 weeks for grade 3-4 events 1

Serious and Life-Threatening Adverse Events

Severe Hypersensitivity Reactions

• Anaphylactic shock can occur even on first exposure to tislelizumab, requiring immediate recognition and intervention 5
• Life-threatening hypersensitivity reactions including serum sickness, angioedema, urticaria, and bronchospasm have been reported 6
• Close monitoring during initial infusions with resuscitation measures immediately available is essential 5

Serious Infections

• Respiratory infection or failure represents one of the most fatal events associated with tislelizumab 3
• Bacterial and viral infections including gastroenteritis, cellulitis, pneumonia, abscess, and sepsis can occur 6
• The rate of serious infections is approximately 3.5% with tislelizumab treatment 6

Treatment-Related Deaths

• Fatal events occur in 3.2-4.2% of patients receiving tislelizumab plus chemotherapy 4
• Deaths are most commonly related to respiratory infection/failure and hepatic injury 3

Serious Treatment-Related Adverse Events

• 23% of patients experience serious treatment-related adverse events in the tislelizumab arm compared to 15% with placebo 1

Management Principles

General Monitoring Strategy

• Monitor white blood cell counts during treatment to detect lymphopenia 6
• Monitor liver enzymes during treatment to identify hepatotoxicity early 6
• Evaluate for concurrent irAEs when any immune-related symptom develops, as fever or other symptoms may signal multi-organ involvement 1, 7

Grade-Based Management Algorithm

For Grade 1-2 irAEs:

• Continue tislelizumab with close monitoring 1
• Some clinicians recommend holding therapy for worrisome grade 2 toxicities (diarrhea, arthritis, dyspnea, hepatitis) 1

For Grade 3 irAEs (excluding stable endocrinopathies on replacement):

• Hold therapy immediately 1
• Start oral high-dose steroids and taper over 4-6 weeks once symptoms resolve 1
• 72% of experts recommend this approach for clinically significant grade 3 irAEs 1

For Grade 4 or Life-Threatening Events:

• Permanently discontinue tislelizumab 1
• Hospitalize patient for specialized care 1
• Initiate aggressive symptomatic treatment including high-dose corticosteroids 1

Specific Toxicity Thresholds for Discontinuation

• Discontinue if ALT or AST >5 times upper limit of normal 6
• Discontinue if bilirubin >3 times upper limit of normal 6
• Discontinue if prolonged severe lymphopenia (<500 cells/mcL lasting ≥1 week) 6
• Discontinue if severe hypersensitivity reactions occur 6

Infection Management

• Use of tislelizumab is not recommended in patients with active serious infection or chronic infection (other than localized skin infections) 6
• Monitor for signs and symptoms of infection during and after treatment 6
• If serious infection develops, treat appropriately and discontinue tislelizumab 6

Critical Pitfalls and Caveats

Delayed Onset Recognition

• irAEs can develop up to 1 year after treatment discontinuation, requiring extended vigilance beyond the treatment period 1
• The unpredictable timing of immune-related toxicities differs from traditional chemotherapy side effects 1

Diagnostic Challenges

• Rule out infection, other drug effects, and systemic diseases before attributing symptoms to tislelizumab 1
• Tissue biopsy may be needed for grade 3-4 toxicities when diagnostic doubt exists 1

Combination Therapy Considerations

• Hematologic toxicities are significantly more common when tislelizumab is combined with chemotherapy versus monotherapy 1
• The incidence of grade ≥3 adverse events increases from individual agent rates to 54% in combination regimens 1

Patient Education Requirements

• Educate patients about immune-related side effects and the importance of promptly reporting symptoms 7
• Patients must understand that symptoms can occur weeks to months after treatment initiation or even after discontinuation 1

Vaccination Timing

• Administer all age-appropriate vaccinations prior to starting tislelizumab 6
• Inactivated or mRNA vaccinations are not recommended within 2 weeks prior to treatment, during treatment, or 6 weeks after completion 6
• Live-attenuated vaccinations are not recommended within 8 weeks prior to treatment, during treatment, or up to 52 weeks after treatment 6