Info
🌱 來自: Huppert’s Notes
Chimeric-Antigen Receptor (CAR)-T cell therapy🚧 施工中
Chimeric-Antigen Receptor (CAR)-T cell therapy
• Mechanism: T cells are collected from the patient and genetically modified with a chimeric antigen receptor (CAR) to direct the T-cells against the tumor cells.
• Indications:
- B-cell ALL, NHL: CAR directed against CD19
- Multiple myeloma: CAR directed against BCMA (B-cell maturation antigen; a cell surface TNF receptor)
• Toxicities:
- Cytokine Release Syndrome (CRS):
• Pathophysiology: Systemic inflammatory response due to cytokine release after CAR-T therapy
• Clinical features: Fever, fatigue, headache, rash, myalgias, diarrhea. Can have very high fevers (104˚F) and can progress to SIRS with hypotension and multi-organ failure. Confusion, lethargy, and even seizures/cerebral edema can occur 2–5 days after onset of CRS and can be progressive. CRS occurs in approximately 25–50% of patients who receive CAR-T cell therapy for B-ALL; less common for patients who receive CAR-T cell therapy for multiple myeloma.
• Diagnosis: ↑CRP and ferritin, dramatic elevation of IL-6. Degree of IL-6 elevation is associated with severity of CRS. See American Society for Transplantation and Cellular Therapy guidelines for grading severity.
• Treatment: Supportive care to manage SIRS. For severe CRS, consider steroids and/or tocilizumab (monoclonal antibody against IL-6) in consultation with the heme/onc team.
- Neurotoxicity:
• Pathophysiology: Not well understood, also thought to be related to cytokine release after CAR-T therapy. Also called ICANS (immune effector cell-associated neurotoxicity syndrome) or CRES (cytokine release encephalopathy syndrome).
• Clinical features: Wide range of symptoms including headache, tremor, expressive aphasia, impaired attention, seizures, cerebral edema. Usually occurs 4–5 days after CAR-T infusion. Can occur independently of CRS.
• Treatment: Steroids are the mainstay of treatment. Should discuss with heme/onc team.