Tisagenlecleucel

Class: CAR-T cell therapy (chimeric antigen receptor T-cell therapy)

Type: Autologous, CD19-directed genetically modified T cells

Mechanism of Action

• Patient’s own T cells are harvested, engineered to express a CAR targeting CD19
• Modified T cells are expanded and reinfused
• Result: T cells recognize and kill CD19+ B cells, including leukemic or lymphoma cells

Indications

• Pediatric and young adult (≤25 years) patients with relapsed/refractory B-cell precursor Acute Lymphoblastic Leukemia (ALL)
• Adults with relapsed/refractory Diffuse Large B-Cell Lymphoma (DLBCL)
• Also approved for Follicular Lymphoma (FL)

Dosing

• Single IV infusion, dose based on weight
  • For ALL:
    • ≤50 kg: 0.2–5.0 × 10⁶ CAR-positive viable T cells/kg
    • 50 kg: 0.1–2.5 × 10⁸ cells total
• Requires lymphodepleting chemotherapy (e.g., fludarabine + cyclophosphamide) prior to infusion

Key Adverse Effects

• Cytokine Release Syndrome (CRS) – most common and serious
• ICANS (Immune effector Cell–Associated Neurotoxicity Syndrome) – confusion, seizures, aphasia
• B-cell aplasia/hypogammaglobulinemia → infection risk
• Prolonged cytopenias
• Infections, TLS, fever, hypotension

Monitoring

• Hospitalize or closely observe for at least 7 days post-infusion
• Monitor:
  • CRS signs (fever, hypotension, hypoxia)
  • Neurologic status (ICANS)
  • CBC, LFTs, renal function, electrolytes
  • CRP, ferritin, IL-6 (if available)

Management of CRS and ICANS

• CRS:
  • Tocilizumab (IL-6 inhibitor) is first-line
  • Corticosteroids if severe or not responsive
• ICANS:
  • Corticosteroids (mainstay); tocilizumab not effective for neurotoxicity

Other Important Notes

• Only available at certified treatment centers (REMS program)
• Long-term monitoring for secondary malignancies and persistent cytopenias
• Patients may require IVIG for hypogammaglobulinemia
• Avoid live vaccines for at least 6 weeks before and after therapy