CAR T-cell Therapy¶
Chelsie Sievers
Background¶
- Chimeric antigen receptor T cells (CAR-T) are a type of autologous T-cell therapy collected from the patient and genetically modified to contain an extracellular tumor-specific antigen target linked to the internal component of the T-cell receptor.
- Goal: patient's own T-cells can specifically target the tumor cell population.
- FDA approved therapies: Kymriah (CD19), Abecema (BCMA), Breyanzi (CD19), Tecartus (CD19), Yescarta (CD19)
Complications¶
- Cytokine Release Syndrome (CRS)
- Pathophysiology: Supraphysiologic immune cell response with
release of inflammatory cytokines.
- Grade 1: fever ≥100.4, no hypotension, no hypoxia
- Grade 2: fever ≥100.4, hypotension not requiring vasopressors and/or hypoxia requiring < 6L
- Grade 3: fever ≥100.4, hypotension requiring a vasopressor, hypoxia requiring >6L or non-rebreather
- Grade 4: fever ≥100.4, hypotension requiring multiple vasopressors, hypoxia requiring positive pressure
- Work-up: blood and urine cultures (IV abx if needed)
- Treatment: acetaminophen for fever, ICU transfer (grade 1 okay for floor), Tocilizumab 8 mg/kg IV (max 800mg; up to 3 doses in 24 hours, 8 hours apart), Dexamethasone 10 mg IV q 6 hours (grade 3-4).
- Pathophysiology: Supraphysiologic immune cell response with
release of inflammatory cytokines.
- ICANS: Immune Effector Cell-Associated Neurotoxicity Syndrome
- Pathophysiology: high systemic inflammation leaky blood brain
barrier encephalopathy ± cerebral edema.
- Based on ICE score: Orientation: orientation to year, month, city, hospital: 4 points; Naming: ability to name 3 objects (eg, point to clock, pen, button): 3 points; Following commands: ability to follow simple commands (eg, “Show me 2 fingers” or “Close your eyes and stick out your tongue”): 1 point; Writing: ability to write a standard sentence (eg, “Our national bird is the bald eagle”): 1 point; Attention: ability to count backwards from 100 by 10: 1 point.
- Grade 1: ICE score: 7-9
- Grade 2: ICE score: 3-6
- Grade 3: ICE score 0-2
- Grade 4: ICE score 0
- Work-up: neuro consult, fundoscopic exam for papilledema, consider MRI brain w/&w/o contrast, consider EEG, consider non-con CT head if headache/lethargy.
- Treatment: q4hr neuro checks (q1hr if grade >2 → ICU transfer), Keep Na 135-145 with hypertonic saline if necessary (Na 145-150 if grade 4), consider thiamine supplementation 500mg q8hrs, Dexamethasone 10 mg q 6 hours (if seizure give 20mg x 1, then 10mg q6hrs) (grade 2-3), Methylprednisolone 1000 mg IV q 24 x 3 days (grade 4).
Last update:
2022-06-25 02:05:01