Grading Toxicity (Overall)
- Asymptomatic or mild symptoms; clinical or diagnostic observation only (headache, fatigue)
- Moderate symptoms; limiting age-appropriate instrumental ADLs (headache, fatigue)
- Severe or medically significant symptoms; limiting self-care ADL (sepsis, severe ataxia)
- Urgent intervention required (sepsis, severe ataxia)
Management
Overall Strategy:
- Ipilimumab to be withheld for any symptomatic hypophysitis and discontinued for symptomatic reactions persisting ≥6 weeks or for inability to reduce steroid dose to ≤7.5 mg prednisone or equivalent per day
- Nivolumab to be withheld for Grade 2/3 hypophysitis and discontinued for Grade 4 hypophysitis. Pembrolizumab to be withheld for Grade 2 hypophysitis and withheld or discontinued for Grade 3/4 hypophysitis
- 1 mg/kg methylprednisolone (or equivalent) IV to be given daily
- If given during acute phase, may reverse inflammatory process
- To be followed with prednisone 1-2 mg/kg daily with gradual tapering over at least 4 weeks
- Long-term supplementation of affected hormones is often required
- Secondary hypothyroidism requiring levothyroxine replacement
- Secondary hypoadrenalism requiring replacement hydrocortisone
- Typical dose: 20 mg qAM and 10 mg qPM
- Assess risk of opportunistic infection based on duration of steroid taper (and consider prophylaxis if needed)
- Collaborative management approach with endocrinology (particularly if permanent loss of organ function)
Nursing Implementation:
- ACTH and thyroid panel should be checked at baseline and prior to each dose of ipilimumab
- Ensure that MRI is ordered with pituitary cuts or via pituitary protocol
- Anticipate treatment with corticosteroid and immunotherapy hold
- Review proper administration of steroid
- Take with food
- Take in AM
- Educate patient regarding possibility of permanent loss of organ function (pituitary; possibly others if involved [thyroid, adrenal glands])
- Sick-day instructions, vaccinations, etc
*Steroid taper instructions/calendar as a guide but not an absolute
- Taper should consider patient’s current symptom profile
- Close follow-up in person or by phone, based on individual need & symptomatology
- Anti-acid therapy daily as gastric ulcer prevention while on steroids
- Review steroid medication side effects: mood changes (anger, reactive, hyperaware, euphoric, mania), increased appetite, interrupted sleep, oral thrush, fluid retention
- Be alert to recurring symptoms as steroids taper down & report them (taper may need to be adjusted)
Long-term high-dose steroids:
- Consider antimicrobial prophylaxis (sulfamethoxazole/trimethoprim double dose M/W/F; single dose if used daily) or alternative if sulfa-allergic (e.g., atovaquone [Mepron®] 1500 mg po daily)
- Consider additional antiviral and antifungal coverage
- Avoid alcohol/acetaminophen or other hepatoxins
RED FLAGS:
- Symptoms of adrenal insufficiency
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