Chimeric antigen receptor T-cell therapy

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Background

  • T cells are retrieved from a patient, genetically modified to add a chimeric antigen receptor (CAR) that is specific to the targetted cancer antigen, and reinfused into the patient following a short course of chemotherapy
  • Used for relapsed or refractory B-cell acute lymphoblastic leukemia and high-grade B-cell lymphoma
Product Indications Target Antigen Survival
Tisagenlecleucel B-ALL and high-grade B-cell lymphoma CD19 76% 1-year OS in B-ALL; 8.3 month median OS in B-cell lymphoma
Axicabtagene ciloleucel high-grade B-cell lymphoma CD19 58% 18-month OS
Brexucabtagene autoleucel mantle cell lymphoma CD19 83% 1-year OS
Idecabtagene vicleucel multiple myeloma B-cell maturation antigen 11.8 month media PFS
Lisocabtagene maraleucal high-grade B-cell lymphoma CD19 18.8 month median OS

Safety

Adverse Effects

  • Prolonged cytopenias and B-cell hypoplasia (causing hypogammaglobulinemia that affects half to two-thirds of patients, some lasting up to 4 years)
  • Loss of immunity to previous vaccinations
    • Start revaccinating about 6 months after infusion

Cytokine Release Syndrome

  • Caused by harmful immune system activation
  • Fever is a defining feature, with hypotension and hypoxia in severe disease
    • Often mimics sepsis
  • May also results in DIC, multiorgan failure, and death
  • Treated with corticosteroids and tocilizumab, an IL-6 inhibitor
  • Usually self-limited

Immune Effector Cell-Associated Neurotoxicity Syndrome

  • ICANS
  • Word-finding difficulty, aphasia, or confusion
  • In severe disease, altered level of consciousness, motor impairment, and cerebral edema
  • Treated with corticosteroids
  • Most cases resolve