Cycle length: Every three weeks, OR every six weeks. Duration of therapy: Until disease progression or unacceptable toxicity. |
Drug | Dose and route | Administration | Given on days |
Pembrolizumab | 200 mg IV | Dilute in NS or D5W¶ to a final concentration between 1 and 10 mg/mL and infuse over 30 minutes through an 0.2- to 5-micron sterile, nonpyrogenic, low-protein-binding inline or add-on filter. | Day 1, every three weeks |
OR |
Pembrolizumab | 400 mg IV | Dilute in NS or D5W¶ to a final concentration between 1 and 10 mg/mL and infuse over 30 minutes through a 0.2- to 5-micron sterile, nonpyrogenic, low-protein-binding inline or add-on filter. | Day 1, every six 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 pembrolizumab in patients with an underlying autoimmune disorder.[2] Pembrolizumab 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 pembrolizumab.
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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 United States Prescribing Information,[1] must be dispensed with this medication.
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Monitoring parameters: |
- CBC with differential and platelet count every three weeks prior to each new cycle of treatment.
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- Assess electrolytes (including glucose) and liver and renal function tests every three weeks prior to each new cycle of treatment. Assess thyroid function tests prior to initiation of therapy and every one to two cycles during treatment, and/or as clinically indicated.
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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 United States Prescribing Information.[1]
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- While immune-mediated toxicities generally occur during treatment with pembrolizumab, 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 at least every three weeks during therapy.
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- No dosage reductions of pembrolizumab 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 pembrolizumab 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 pembrolizumab-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 pembrolizumab,[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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