Indications

Acute Lymphoblastic Leukemia (see xxxx)

Clinical Efficacy

• ELIANA Trial of Tisagenlecleucel in Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (ALL (NEJM, 2018) [MEDLINE]
  • In this global study of CAR T-cell therapy, a single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B-cell ALL, with transient high-grade toxic effects

B-Cell Lymphoma (see Lymphoma)

Clinical Efficacy

• JULIET Trial of Tisagenlecleucel in B-Cell Lymphoma (NEJM, 2019) [MEDLINE]
  • In this Trial in Relapsed or refractory diffuse large B-cell lymphoma in adults, high rates of durable responses were produced with the use of tisagenlecleucel

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Contraindications

• Graft vs Host Disease (GVHD) (see xxxx)

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Pharmacology

CD19-Directed T-Cell Medication

• xxx

Metabolism

• xxx

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Administration

Intravenous (IV)

• xxx

Dose Adjustment

• Hepatic: xxx
• Renal: xxx

Use in Pregnancy (see Pregnancy)

• xxx

Use in Lactation

• xxx

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Adverse Effects

Cytokine Release Syndrome (see Cytokine Release Syndrome)

Epidemiology

• Median Time to Onset: 3 days (range: 1-22 days)
• Risk Factors
  • Active Inflammatory Processes
  • High Pre-Infusion Tumor Burden (>50% Blasts in BIne Marrow)
  • Infection

Clinical

• Cardiovascular Manifestations
  • Hypotension (see Hypotension)
• Gastrointestinal Manifestations
  • Diarrhea (see Diarrhea)
• Pulmonary Manifestations
  • Dyspnea (see Dyspnea)
  • Hypoxemia/Acute Respiratory Failure (see Hypoxemia and Respiratory Failure)
  • Pulmonary Infiltrates (see xxxx)
• Other Manifestations
  • Fever (see Fever)

Treatment

• Supportive Care
  • Intravenous Fluids (see Normal Saline)
  • Vasopressors
  • Respiratory Support with Invasive Mechanical Ventilation (see Invasive Mechanical Ventilation-General)
• Tocilizumab (XXXXXXXXXXXX) (see Tocilizumab)
  • First-Line Treatment
  • Maximum of 4 Doses
• Corticosteroids (see Corticosteroids)
  • Since Corticosteroids May Compromise the Clinical Effectiveness of Treatment (Due to Their Lympholytic Effect), Corticosteroids are Generally Reserved as Second-Line Therapy of Life-Threatening Reactions
  • XXXX

Neurologic Adverse Effects

Epidemiology

• Most Neurologic Toxicity Occurs within 8 wks of Treatment
• May Occur with/without Cytokine Release Syndrome

Clinical

• Anxiety (see Anxiety)
  • Less Common Neurologic Manifestation
• Aphasia (see Aphasia)
  • Less Common Neurologic Manifestation
• Dizziness (see Dizziness)
  • Less Common Neurologic Manifestation
• Encephalopathy/Delirium (see Delirium)
  • Less Common Neurologic Manifestation
• Headache (see Headache)
  • Less Common Neurologic Manifestation
• Seizures (see Seizures)
  • Less Common Neurologic Manifestation

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References

• ELIANA Trial. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018 Feb 1;378(5):439-448. doi: 10.1056/NEJMoa1709866 [MEDLINE]
• JULIET Trial. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2019 Jan 3;380(1):45-56. doi: 10.1056/NEJMoa1804980 [MEDLINE]
• Patient-reported quality of life after tisagenlecleucel infusion in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: a global, single-arm, phase 2 trial. Lancet Oncol. 2019 Dec;20(12):1710-1718. doi: 10.1016/S1470-2045(19)30493-0 [MEDLINE]
• Real-world evidence of tisagenlecleucel for pediatric acute lymphoblastic leukemia and non-Hodgkin lymphoma. Blood Adv. 2020 Nov 10;4(21):5414-5424. doi: 10.1182/bloodadvances.2020003092 [MEDLINE]