Cycle length: Every two weeks, OR every four weeks.
Duration of therapy: Until disease progression or unacceptable toxicity. |
| Drug | Dose and route | Administration | Given on days |
| Nivolumab | 240 mg IV | Dilute with either NS or D5W¶ to a final concentration between 1 and 10 mg/mL; total infusion volume should not exceed 160 mL. Infuse over 30 minutes through an IV line containing a sterile, nonpyrogenic, low-protein binding inline filter (pore size of 0.2 to 1.2 micrometer). | Day 1, every two weeks |
| ORΔ |
| Nivolumab | 480 mg IV | Dilute with either NS or D5W¶ to a final concentration between 1 and 10 mg/mL; total infusion volume should not exceed 160 mL. Infuse over 30 minutes through an IV line containing a sterile, nonpyrogenic, low-protein binding inline filter (pore size of 0.2 to 1.2 micrometer). | Day 1, every four weeks |
| Pretreatment considerations: |
| Immune status | - Anti-PD-1 monoclonal antibodies generate an immune response that may aggravate underlying autoimmune disorders or prior immune-related adverse events. There are only limited data on the safety and efficacy of checkpoint inhibitors such as nivolumab in patients with an underlying autoimmune disorder.[2] Nivolumab should be used with extreme caution in such individuals.
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| Emesis risk | - Minimal.
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Prophylaxis for infusion reactions | - There is no standard premedication regimen for nivolumab.
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| Infection prophylaxis | - Primary prophylaxis with G-CSF is not indicated (estimated risk of febrile neutropenia is <5%).
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| Dose adjustment for baseline liver or renal dysfunction | |
| Thyroid function tests | - Assess baseline thyroid function tests (TSH, FT4) prior to initiation of therapy.
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| Regulatory issues | - An FDA-approved patient medication guide, which is available with the US Prescribing Information,[1] must be dispensed with this medication.
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| Monitoring parameters: |
- CBC with differential and platelet count prior to each new cycle of treatment.
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- Assess electrolytes (including glucose) and liver, renal, and thyroid function tests every two or four weeks or prior to each new cycle of treatment.
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- Monitor for fatigue, colitis, hepatotoxicity, hypophysitis, adrenal insufficiency, hypo- or hyperthyroidism, nephrotoxicity, pneumonitis, hyperglycemia, and skin rash. Many other clinically relevant immune-mediated toxicities have been observed, which may involve any organ system or tissue, and may be severe or fatal.
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- Monitor for infusion reactions during treatment. Interrupt infusion and permanently discontinue for severe or life-threatening infusion-related reactions, as indicated in the US Prescribing Information.[1]
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- While immune-mediated toxicities generally occur during treatment with nivolumab, adverse reactions, including infusion-related reactions, may also develop weeks to months after therapy discontinuation.
- Refer to UpToDate topics on toxicities associated with checkpoint inhibitor immunotherapy.
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| Suggested dose modifications for toxicity: |
- All patients should be closely monitored and evaluated for immune-mediated adverse effects prior to each dose.
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- No dosage reductions of nivolumab are recommended; treatment is withheld or discontinued to manage toxicities.
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- In general, if an immune-mediated adverse event is suspected, evaluate appropriately to confirm or exclude other causes. Based on the type and severity of the reaction, withhold treatment and administer systemic glucocorticoids. Upon resolution to ≤grade 1, initiate glucocorticoid taper. Immune-mediated adverse reactions that do not resolve with systemic glucocorticoids may be managed with other systemic immunosuppressants (based on limited data). Discontinue nivolumab permanently for any grade 4 or recurrent grade 3 immune-mediated adverse event or one that is life threatening, grade 3 pneumonitis, AST/ALT elevation >8 times ULN, total bilirubin elevation >3 times ULN in patients with no hepatic tumor involvement, AST/ALT elevation to >10 times ULN for hepatitis with hepatic tumor involvement, grade ≥2 myocarditis, grade 3 neurologic toxicity, suspected exfoliative dermatologic condition, severe (grade 3) or life-threatening (grade 4) infusion reactions, or if there is an inability to reduce glucocorticoid dose to 10 mg or less of prednisone equivalent per day within 12 weeks of initiating glucocorticoids.[1]
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- Most nivolumab-associated rashes can be managed with topical corticosteroid creams.
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- Guidelines for managing specific toxicities, including immune-mediated adverse events, are available in the United States Prescribing Information for nivolumab,[1] from ASCO,[3] from the MASCC,[4] from the NCCN,[5] and from the SITC.[6]
- Refer to UpToDate topics on toxicities associated with checkpoint inhibitor immunotherapy.
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