Immunotherapy neurological toxicity

 1. Grade the toxicity

2. Triage:  next day evaluation in clinic/ hospital admission/ICU

3. Initial investigations: cultures, inflammatory markers, hormone level, antibodies

4. Medication management: stop the immunotherapy, start steroids, need for antibiotic, antivirals

5. Specialist consultation : Typically if pt is sick to be in a hospital, then consult appropriate specialist

Toxicity grading 

Instrumental ADL ( if these are affected, it is at least grade 2): evaluation in clinic in 24-48 hr

• Shopping, finance, communicating via email or phone, taking medications,  driving, taking public transportation, doing laundry, cleaning hom

Self care ADL ( typically grade 3)à ER or same day evaluatio

• dressing, bathing, hygiene, eating, toileting, cooking, ability to move within the home without assistance or falls

Grade 4 toxicity: severe symptoms

Specialist consultation

Patients should be referred to a specialist when they experience toxicities of grade ≥3, if toxicities of any grade do not respond to steroid treatment, if toxicities require hospitalization or for selected lower-grade toxicities in which diagnosis or management advice is needed, such as neurological and rheumatological toxicities (eg, inflammatory arthritis not interfering with instrumental activities of daily living, mild pain with erythema, or joint swelling).

Neurological toxicity- permanently discontinue immunotherapy. Neurology consultation.

Conditions: Myasthenia gravis, GBS, peripheral neuropathy, autonomic neuropathy, aseptic meningitis, encephalitis, multiple sclerosis like presentation

Myasthenia:

1. Work-up and evaluation: Acetylcholine receptor antibodies. If neg, and with neurology input MuSK and LPR4 antibodies. The absence of antibodies does not rule out the syndrome.
2. Very important to consider 3M syndrome- myasthenia, myocarditis, myositis.
3. Myositis work up-CK, aldolase, ESR, CRP
4. Myocarditis work up- telemetry, EKG, Echo ( can be normal), troponin I and T, cardiac MRI
5. Review and stop medications with known risk of worsening myasthenia: beta-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics
6. MRI brain and spine, LP, paraneoplastic work up

Treatment

1. low dose Steroids: typical dose 1 mg/kg bwt except with myasthenia use lower dose of 0.5 mg/kg bwt

2. IVIG 2 gm/kg bwt daily 5 days or PLEX

3. Plasma exchange (PLEX)

4. Rituximab if refractory to IVIG or PLEX

 Given the high rate of fatality for patients who develop myasthenia gravis (20%) or myocarditis (17%), suspicion of one or more of these irAEs should prompt evaluation for all three.

GBS- Corticosteroids are usually not recommended for idiopathic GBS; however, in ICPi-related forms, a trial is reasonable (methylprednisolone 2 to 4 mg/kg/day), followed by slow steroid taper. Neuro checks. Monitor for autonomic dysfunction. Avoid opiates for pain.

Aseptic meningitis/ Encephalitis: IV acyclovir pending ruling out direct or paraneoplastic malignancy as the cause rather than ICP toxicity.

Uptodate is a great resource.

References: 

https://pmc.ncbi.nlm.nih.gov/articles/PMC9683636/

https://myasthenia.org/wp-content/uploads/Portals/0/MGFA%20Classification.pdf