CAR T-cell Therapy

Chelsie Sievers

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Background

• Chimeric antigen receptor T cells (CAR-T) are a type of autologous T-cell therapy collected from the pt and genetically modified to contain an extracellular tumor-specific antigen target linked to the internal component of the T-cell receptor.
• Goal: Pt'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
  • Pathophysiology: Supraphysiologic immune cell response with release of inflammatory cytokines.
  • Grading
    • 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:
    • ICU transfer (grade 1 okay for floor)
    • Acetaminophen for fever
    • 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)
• Immune effector cell-associated neurotoxicity syndrome: ICANS
  • Pathophysiology: high systemic inflammation -> leaky blood brain barrier -> encephalopathy ± cerebral edema
  • Grading
    • Based on ICE score: Orientation: orientation to year, month, city, hospital (4 points); Naming: ability to name 3 objects (e.g. point to clock, pen, button) (3 points); following commands: ability to follow simple commands (e.g. “Show me 2 fingers” or “Close your eyes and stick out your tongue”) (1 point); writing: ability to write a standard sentence (e.g. “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/and 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 q8hr
    • Steroids
      • Grade 2-3: dexamethasone 10 mg q 6 hours (if seizure give 20mg x 1, then 10mg q6hrs)
      • Grade 4: methylprednisolone 1000 mg IV q 24 x 3 days