Tisagenlecleucel — Drug Monograph
Brand names: Kymriah
Drug class: Other
Mechanism of Action
Tisagenlecleucel is an autologous CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy. Patient T cells are harvested via leukapheresis, then genetically engineered ex vivo to express a CAR containing an anti-CD19 scFv fused to 4-1BB and CD3ζ signaling domains. Upon reinfusion, the CAR-T cells recognize and bind CD19 on malignant B cells, triggering T-cell activation, proliferation, and cytolytic killing. The 4-1BB costimulatory domain promotes sustained in vivo persistence and memory formation. Lymphodepletion with fludarabine and cyclophosphamide prior to infusion enhances…
FDA Indications
- Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in patients up to 25 years of age (FDA approved August 2017)
- Relapsed or refractory large B-cell lymphoma (DLBCL, high-grade B-cell lymphoma, DLBCL arising from follicular lymphoma) after two or more lines of systemic therapy in adults (FDA approved May 2018)
Common Side Effects
- Pyrexia
- Cytokine release syndrome (any grade)
- Hypotension
- Nausea and vomiting
- Fatigue
- Headache
- Decreased appetite
- Febrile neutropenia
- Diarrhea
- Hypoxia
Clinical Pearl
Approximately 1-month manufacturing lead time requires early referral planning. Bridging therapy may be required for aggressive disease. B-cell aplasia is a surrogate for ongoing CAR-T activity but necessitates indefinite IVIG replacement. Tocilizumab should be available at bedside before infusion begins.
Related Therapies & Mechanisms
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