This is a new type of cancer treatment for certain malignancies where a patient’s blood undergoes apheresis to isolate the T-cells. These undergo gene insertion to express Chimeric Antigen Receptors for the specified target cancer. Cells are propagated in vitro then infused back into the patient where they target and kill the cancer cells.

Key complications: CRS and ICANS

CRS – Cytokine Release Syndrome

• Clinical features
  • Fever & flu-like symptoms
    • Fever >38oC (required for Dx)
    • Chills, rigors, headaches
    • Myalgias
    • Nausea, vomiting, diarrhoea
  • Cardiac features
    • Sinus tachycardia
    • Arrhythmias – AF, VT
    • Shock – distributive due to SIRS
    • Shock – cardiogenic due to new-onset cardiomyopathy
  • Respiratory features
    • resp failure sometimes necessitating intubation
  • Renal
    • AKI
  • Skin
    • Skin rashes may be seen
  • Haematological
    • DIC
    • HLH (Haemophagocytic Lymphohistiocytosis)
      • Occurs in underlying DLBCL or B-ALL
      • Ferritin profoundly elevated
      • Hepatomegaly and/or splenomegaly
      • Cytopaenias
      • Persistent fevers
      • Hyperfibrinolysis (low fib, high d-dimer)
      • Hypertriglyceridaemia
      • Haemophagocytosis on biopsy (Bone Marrow)
      • Failure to respond to standard CRS therapy
• Treatment
  • Dexamethasone 10mg Q6h (crosses BBB)
    • if refractory –> Pulsed methylprednisolone 1g Daily x3
  • Tocilizumab (doesn’t cross BBB)
  • Avoid GM-CSF – may exacerbate CRS
  • General Rx of shock in this patient cohort
    • Vasopressors / Inotropes
    • Broad spectrum antibiotics
    • Consider antifungals
    • Paracetamol for fever
  • super-refractory CRS:
    • Anakinra or Ruxolitinib
    • consider HLH as a DDx (but Rx is still with anakinra/ ruxolitinib)
      • Etoposide last resort – kills the T cells

ICANS – Immune-effector-Cell-Associated Neurotoxicity Syndrome

• Clinical features
  • Fluctuating symptoms
  • Language
    • Dysgraphia +/- expressive dysphasia
    • Expressive aphasia progressing to global aphasia very suggestive of ICANS
  • Motor
    • Tremor
    • Fine motor impairment
    • Asterixis
    • Myoclonus
    • Focal or generalised weakness may occur
  • Consciousness
    • Altered
    • Classic: “encephalopathy with preserved alertness”
  • Headache +/- meningism
  • Seizures (including status)
  • Rarely clinical features of cerebral oedema
• Management
  • As for CRS, but HOLD THE TOCILIZUMAB
    • does not cross BBB
    • inhibits IL-6
    • IL-6 may spill over into brain
    • may worsen ICANS
  • Seizure prevention
    • Withhold medications which lower seizure threshold
    • Levetiracetam
  • High dose thiamine
  • Generic treatment of raised ICP if present