Tisagenlecleucel (Kymriah)

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

Contraindications

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

Pharmacology

CD19-Directed T-Cell Medication

  • xxx

Metabolism

  • xxx

Administration

Intravenous (IV)

  • xxx

Dose Adjustment

  • Hepatic: xxx
  • Renal: xxx

Use in Pregnancy (see Pregnancy)

  • xxx

Use in Lactation

  • xxx

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

Treatment

  • Supportive Care
  • 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

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]