Management of Atezolizumab-Induced Immune-Mediated Encephalitis
High-dose corticosteroids should be initiated immediately upon suspicion of atezolizumab-induced immune-mediated encephalitis, with methylprednisolone 1-4 mg/kg/day for moderate cases or pulse-dose methylprednisolone (1g daily for 5 days) for severe cases. 1
Diagnosis
Early recognition is critical for successful management. Key diagnostic steps include:
Rule out other causes of neurological symptoms:
- CNS progression of cancer
- Seizure activity
- Infection
- Metabolic derangement 1
Neurological consultation is mandatory for all grade 2 or higher neurologic immune-related adverse events 1
Diagnostic workup:
- MRI of the brain with and without contrast
- CSF analysis including:
- Cell count (may show lymphocytic pleocytosis)
- Protein (often elevated)
- Glucose
- Cytology (to rule out leptomeningeal metastasis)
- PCR for infectious causes 1
- EEG to rule out seizure activity 1
- Consider autoimmune encephalitis and paraneoplastic antibody panels 1
Clinical Presentation
Patients with atezolizumab-induced encephalitis typically present with:
Most cases occur within 2-3 weeks after treatment initiation, with several reported cases developing symptoms around days 13-17 after the first dose of atezolizumab 2, 3, 5.
Treatment Algorithm
Grade 1 (Mild Symptoms):
- Close observation
- May continue checkpoint inhibitor therapy under careful monitoring 1
Grade 2 (Moderate Symptoms):
- Hold atezolizumab therapy
- Start corticosteroids: methylprednisolone 1-2 mg/kg/day 1
- Monitor for improvement
Grade 3-4 (Severe Symptoms):
- Permanently discontinue atezolizumab 1
- Initiate high-dose corticosteroids:
- Consider escalation therapy if inadequate response:
- Monitor response with repeat CSF analysis and clinical assessment 2
Treatment Duration and Follow-up
- Continue steroid treatment until clinical improvement is observed
- Taper steroids gradually over several weeks to prevent relapse
- Monitor for neurological improvement daily
- Repeat CSF analysis to confirm normalization of parameters (typically within 10-14 days) 2
- Schedule follow-up neurological assessments after discharge
Prognosis
With prompt recognition and appropriate treatment, most patients with atezolizumab-induced encephalitis have favorable outcomes:
- Symptoms typically begin to improve within days of starting high-dose steroids 2, 3
- Complete resolution without neurological sequelae is possible with timely intervention 2
- CSF parameters usually normalize within 2 weeks 2
Important Considerations and Pitfalls
- Delay in treatment beyond 48 hours after symptom onset may lead to poorer outcomes 6
- Normal brain imaging does not rule out immune-mediated encephalitis, as MRI may show no abnormalities in some cases 2
- CSF findings may include elevated protein with normal or mildly elevated cell count 5
- Elevated IL-6 levels in CSF may reflect the severity of encephalitis and can be used as a marker 2
- Immunocompromised patients may have more subtle presentations and require prolonged treatment 1
- Consider screening for other immune-mediated adverse events, as they may occur concurrently
Prevention of Recurrence
- Permanent discontinuation of atezolizumab and other PD-L1/PD-1 inhibitors is recommended after severe immune-mediated encephalitis 1
- Consider alternative cancer treatment strategies in consultation with the oncology team
By following this management approach, clinicians can effectively address atezolizumab-induced immune-mediated encephalitis and minimize the risk of long-term neurological sequelae.