Tisagenlecleucel
Identification
- Summary
Tisagenlecleucel is a CAR T cell therapy for relapsed or refractory large B-cell lymphoma and diffuse large B-cell lymphoma.
- Brand Names
- Kymriah
- Generic Name
- Tisagenlecleucel
- DrugBank Accession Number
- DB13881
- Background
Tisagenlecleucel is a CD19-directed genetically modified autologous T cell immunotherapy, or a CAR-T cell therapy for B-cell acute lymphoblastic leukemia. It was granted approval by FDA in August 2017 under the market name Kymriah. Tisagenlecleucel is an immunocellular therapy that involves autologous T cells that are collected from each individual patient and genetically engineered to express a specific protein called a chimeric antigen receptor (CAR) that specifically target CD19 antigens. Modified T cells are infused back into the patient's body. These CD19-directed chimeric antigen receptors (CD19 CAR-T cells) direct the T cells to target and kill leukemia cells that express CD19 on the cell surface.
In a multicenter clinical trial involving pediatric and young adult patients with relapsed or refractory B-cell precursor ALL, the overall remission rate within three months of treatment was 83 percent.4
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Cell transplant therapies
Autologous cell transplant - Synonyms
- Adoptive immunotherapy agent CTL019
- CAR.CD19-Redirected T cells
- Tisagenlecleucel
- Tisagenlecleucel-T
- External IDs
- CART-19
- CART19
- CTL-019
- CTL019
Pharmacology
- Indication
Tisagenlecleucel is indicated for use in individuals aged 25 years and younger with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.5
It is also used to treat adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.5
Tisagenlecleucel is also indicated in adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.5
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Refractory diffuse large b cell lymphoma (dlbcl) •••••••••••• ••••• ••••• •• ••••• •• •••••••• ••••••• •••••••••• •••••••••• Treatment of Refractory follicular lymphoma •••••••••••• ••••• ••••• •• ••••• •• •••••••• ••••••• •••••••••• •••••••••• Treatment of Relapsed diffuse large b-cell lymphoma (dlbcl) •••••••••••• ••••• ••••• •• ••••• •• •••••••• ••••••• •••••••••• •••••••••• Treatment of Relapsed follicular lymphoma •••••••••••• ••••• ••••• •• ••••• •• •••••••• ••••••• •••••••••• •••••••••• Treatment of Refractory b-cell precursor acute lymphoblastic leukemia •••••••••••• ••••••••••• •••••• ••••••••• •••••••••• •••••••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Tisagenlecleucel demonstrates efficacy in re-inducing remission in patients with refractory B-cell precursor acute lymphoblastic leukemia. The sole purpose of the therapy is to eliminate CD19-expressing malignant and normal cells with specificity and increased chance of remission.
- Mechanism of action
Tisagenlecleucel is a CD19-directed genetically modified autologous T cell immunotherapy that involves genetically modified autologous T cells isolated from each individual patient. The reprogramming of the patient's T cells uses a lentiviral vector to encode an anti-CD19 chimeric antigen receptor (CAR). The CAR is comprised of a murine single-chain antibody fragment (scFv) specific for CD19, followed by a CD8 hinge and transmembrane region that is fused to the intracellular signaling domains from 4-1BB (CD137) and CD3 zeta.5 These intracellular costimulatory signaling domains increase the expansion, longer-term persistence and potency of CAR T cells1,3; the CD3 zeta component is critical for initiating T-cell activation and antitumor activity, while 4-1BB enhances the expansion and persistence of tisagenlecleucel.5,2 Upon binding to CD19-expressing cells, the CAR transmits a signal to promote T-cell expansion, activation, target cell elimination, and persistence of the tisagenlecleucel cells.5
Target Actions Organism AB-lymphocyte antigen CD19 antibodyHumans - Absorption
In pediatric and young adult relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) patients receiving tisagenlecleucel infusion, the mean peak plasma concentration was approximately 34,700 copies/mcg with a median time of 9.91 days to reach this value (Tmax).5
- Volume of distribution
The drug is found to be distributed in the blood as well as the bone marrow. Blood to bone marrow partitioning suggested that tisagenlecleucel distribution in bone marrow was 44% of that present in blood at Day 28 while at Months 3 and 6 tisagenlecleucel distributed at 67% and 69%, respectively, indicating high distribution to bone marrow.5
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
The mean half life was 16.8 days in pediatric and young adult relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) patients.5
- Clearance
Not Available
- Adverse Effects
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- Toxicity
Genotoxicity assay, carcinogenicitiy assay, and studies assesssing the effect of drug on fertility have not been conducted for tisagenlecleucel. According to in vitro T cell expansion studies involving transduced T cells from healthy donors and patients, there is no evidence of transformation and immortality.5
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAmbroxol The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Bupivacaine. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Kymriah Injection, suspension 60000000 1/1 Intravenous Novartis Pharmaceuticals Corporation 2018-05-01 Not applicable US Kymriah 300600000 cells Intravenous Novartis Europharm Limited 2020-12-16 Not applicable EU Kymriah Injection, suspension 2000000 1/1 Intravenous Novartis Pharmaceuticals Corporation 2017-08-30 Not applicable US Kymriah Suspension 600000000 cells Intravenous Novartis 2019-05-24 Not applicable Canada
Categories
- ATC Codes
- L01XL04 — Tisagenlecleucel
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Antineoplastic and Immunomodulating Agents
- Antineoplastic cell and gene therapy
- Cancer immunotherapy
- CD19 Receptor Interactions
- CD19-directed Chimeric Antigen Receptor
- Genetically-modified Autologous T Cells
- Immunotherapy
- Membrane Proteins
- Proteins
- Receptors, Antigen
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- Q6C9WHR03O
- CAS number
- 1823078-37-0
References
- General References
- Tasian SK, Gardner RA: CD19-redirected chimeric antigen receptor-modified T cells: a promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL). Ther Adv Hematol. 2015 Oct;6(5):228-41. doi: 10.1177/2040620715588916. [Article]
- Wei G, Ding L, Wang J, Hu Y, Huang H: Advances of CD19-directed chimeric antigen receptor-modified T cells in refractory/relapsed acute lymphoblastic leukemia. Exp Hematol Oncol. 2017 Apr 14;6:10. doi: 10.1186/s40164-017-0070-9. eCollection 2017. [Article]
- Davila ML, Brentjens RJ: CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia. Clin Adv Hematol Oncol. 2016 Oct;14(10):802-808. [Article]
- FDA Press Announcements: FDA approval brings first gene therapy to the United States [Link]
- FDA Approved Drug Products: Kymriah (tisagenlecleucel) suspension for intravenous infusion [Link]
- External Links
- PubChem Substance
- 347911451
- 1986438
- Wikipedia
- Tisagenlecleucel
- FDA label
- Download (222 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Non-Hodgkin's Lymphoma (NHL) 1 3 Completed Treatment Acute Lymphoblastic Leukaemias (ALL) 1 3 Recruiting Treatment B-cell Acute Lymphoblastic Leukemia / Diffuse Large B-Cell Lymphoma (DLBCL) 1 3 Recruiting Treatment Follicular Lymphoma ( FL) 1 3 Withdrawn Treatment Acute Lymphoblastic Leukaemias (ALL) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, suspension Intravenous 2000000 1/1 Injection, suspension Intravenous 300600.000 cells Injection, suspension Intravenous 60000000 1/1 Suspension Intravenous 600000000 cells - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antibody
- General Function
- Receptor signaling protein activity
- Specific Function
- Assembles with the antigen receptor of B-lymphocytes in order to decrease the threshold for antigen receptor-dependent stimulation.
- Gene Name
- CD19
- Uniprot ID
- P15391
- Uniprot Name
- B-lymphocyte antigen CD19
- Molecular Weight
- 61127.985 Da
Drug created at September 01, 2017 18:43 / Updated at July 02, 2022 14:09