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Kymriah

tisagenlecleucel
CAR T-Cell Therapy (CD19-targeted) FDA Approved 2017 Novartis
1. Indications and Usage

B-cell precursor acute lymphoblastic leukemia (ALL) — in patients up to 25 years of age with refractory disease, in second or later relapse, or relapse post-transplant; Large B-cell lymphoma — relapsed or refractory after two or more lines of systemic therapy (DLBCL NOS, high-grade B-cell lymphoma, DLBCL arising from FL); Follicular lymphoma (FL) — relapsed or refractory after two or more lines of systemic therapy

2. Dosage and Administration

B-cell ALL (≤50 kg): 0.2-5.0 × 10⁶ CAR-positive viable T cells/kg
B-cell ALL (>50 kg): 0.1-2.5 × 10⁸ total CAR-positive viable T cells
DLBCL: 0.6-6.0 × 10⁸ CAR-positive viable T cells (non-weight-based)
FL: 0.6-6.0 × 10⁸ CAR-positive viable T cells
Lymphodepleting chemo: Fludarabine 30 mg/m² IV × 4 days + cyclophosphamide 500 mg/m² IV × 2 days (or bendamustine 90 mg/m² IV × 2 days)
Pre-medication: Acetaminophen and diphenhydramine 30-60 min prior

3. Dosage Forms and Strengths

Cell suspension for IV infusion in a patient-specific infusion bag(s). Dose varies by indication and weight.

4. Contraindications

Refer to the complete prescribing information for contraindications. Kymriah prescribing should account for patient-specific factors including hypersensitivity to the active ingredient or any excipients.

5. Warnings and Precautions
⚠ Boxed Warning
CYTOKINE RELEASE SYNDROME (CRS): Including fatal or life-threatening reactions. Ensure tocilizumab available prior to infusion. NEUROLOGIC TOXICITIES: Including fatal or life-threatening reactions. Monitor and manage promptly.
  • CRS: ALL: 79% (27% Grade ≥3); DLBCL: 57% (15% Grade ≥3). Median onset: 3 days. Ensure 2 doses tocilizumab available.
  • Neurologic Toxicities: ALL: 39% (13% Grade ≥3); DLBCL: 21% (10% Grade ≥3). Including encephalopathy, confusion, seizures.
  • Infections: 48% in ALL, 34% in DLBCL. Including life-threatening or fatal infections.
  • Prolonged Cytopenias: 32-49% not resolved by Day 28.
  • Hypogammaglobulinemia: 43% in ALL, 15% in DLBCL. Monitor and replace Ig.
  • Secondary Malignancies: Including myeloid neoplasms and T-cell lymphoma.
  • HLH/MAS: Potentially life-threatening.
6. Adverse Reactions
Most Common Adverse Reactions

CRS (57-79%), infections (34-48%), decreased appetite (24-33%), headache (25-37%), encephalopathy (17-34%), hypotension (20-26%), febrile neutropenia (14-35%), tachycardia (14-26%), fatigue (26-29%), nausea (21-26%)

Key Safety Signals

CRS: ALL 79% (27% Grade 3+), DLBCL 57% (15% Grade 3+). Neurotoxicity: ALL 39% (13% Grade 3+). Prolonged cytopenias not resolved by Day 28: 32-49%. Hypogammaglobulinemia: 43% ALL, 15% DLBCL.

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

7. Drug Interactions

Key Safety Signals

CRS: ALL 79% (27% Grade 3+), DLBCL 57% (15% Grade 3+). Neurotoxicity: ALL 39% (13% Grade 3+). Prolonged cytopenias not resolved by Day 28: 32-49%. Hypogammaglobulinemia: 43% ALL, 15% DLBCL.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

8. Use in Specific Populations
Pregnancy

Consult the full prescribing information for pregnancy-related considerations.

Lactation

Refer to prescribing information for lactation guidance.

Pediatric Use

Pediatric safety and efficacy information is detailed in the full label.

Hepatic/Renal Impairment

Dose modifications for organ impairment are specified in the complete prescribing information.

12. Clinical Pharmacology
Mechanism of Action

Tisagenlecleucel is a CD19-directed genetically modified autologous T-cell immunotherapy. Patient T cells are transduced with a lentiviral vector encoding a CAR composed of an anti-CD19 scFv linked to 4-1BB (CD137) costimulatory and CD3-zeta signaling domains. The 4-1BB costimulatory domain enhances T-cell persistence and expansion. Upon binding CD19-positive cells, the CAR T cells activate and eradicate target cells.

Pharmacokinetics

Peak CAR T-cell expansion: median 10 days (ALL), 9 days (DLBCL). Transgene detectable in blood for up to 2 years. Higher peak expansion correlated with response. 4-1BB costimulatory domain promotes long-term T-cell persistence.

14. Clinical Studies

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

Pivotal Clinical Trials
Additional Resources
FDA-Approved Tumor Types

Kymriah has FDA-approved indications across the following cancer types covered on PipelineEvidence:

External Resources
Important Notice: This page is intended as a navigational reference to the FDA-approved prescribing information for Kymriah. It does not replace the full prescribing information. Healthcare professionals should consult the complete package insert available at DailyMed before making prescribing decisions. Patient-specific factors should always guide clinical decision-making.