How to manage Nivolumab (nivolumab)-induced fever?

Management of Nivolumab-Induced Fever

For nivolumab-induced fever, management should be based on fever severity, with mild fever (<38.5°C) managed with antipyretics while continuing therapy, moderate fever (38.5-40°C) requiring temporary treatment interruption, and severe fever (>40°C) necessitating immediate nivolumab discontinuation and corticosteroid therapy. 1

Grading and Initial Management

• Grade 1 (mild fever <38.5°C):

  • Continue nivolumab therapy with close monitoring
  • Administer acetaminophen as needed for symptom relief 1
  • Monitor for development of additional immune-related adverse events (irAEs) 1

• Grade 2 (moderate fever 38.5-40°C):

  • Temporarily withhold nivolumab until fever resolves
  • Administer antipyretics on a scheduled basis
  • Rule out infection with appropriate cultures and imaging
  • Monitor renal function, liver enzymes, and complete blood count to detect early signs of other irAEs 1

• Grade 3-4 (severe fever >40°C or fever with complications):

  • Immediately withhold nivolumab
  • Initiate high-dose corticosteroids
  • Consider hospitalization for monitoring and supportive care 1

Evaluation for Concurrent Immune-Related Adverse Events

• Fever may be the first sign of a more serious immune-mediated reaction, requiring thorough evaluation for:

  • Pneumonitis - assess for cough, dyspnea, or respiratory symptoms 1, 2
  • Encephalitis - monitor for altered mental status, confusion, or neurological symptoms 1, 3
  • Immune thrombocytopenia - check complete blood count 1, 4
  • Cytokine release syndrome - watch for hypotension, hypoxemia, or multi-organ dysfunction 1, 5

• Be vigilant for fever accompanied by specific organ-related symptoms that may indicate serious irAEs 1

Management of Recurrent Fever

• Consider premedication with antipyretics for subsequent nivolumab doses if fever recurs 1
• Evaluate for permanent discontinuation of nivolumab if fever recurs despite premedication, especially if accompanied by other significant irAEs 1
• After resolution of fever, closely monitor for recurrence when restarting nivolumab or tapering steroids 1

Special Considerations

• Patients with pre-existing autoimmune conditions may be at higher risk for developing fever and other irAEs 1
• Consider prophylactic antibiotics in patients requiring prolonged immunosuppression with corticosteroids 1
• Document the reaction thoroughly to guide management of future nivolumab doses 1

Patient Education

• Educate patients about possible immune-related side effects, including fever 1
• Emphasize the importance of promptly reporting fever or any new symptoms 1
• Inform patients that fever may signal the onset of conditions such as immune-mediated nephritis, thrombocytopenia, or encephalitis 1

Clinical Pearls and Pitfalls

• Fever following nivolumab administration can rapidly progress to more serious conditions like cytokine release syndrome if not properly managed 5
• Non-infectious fever is a common side effect of immune checkpoint inhibitors and should prompt evaluation for underlying immune-related adverse events 6
• Hyponatremia may accompany fever in patients receiving nivolumab, potentially due to volume depletion or endocrinopathies 6
• The incidence of infusion reactions with PD-1/PD-L1 inhibitors is generally low (<1% of adverse events) but can increase significantly when combined with other therapies 1