Lisocabtagene maraleucel
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Identification
- Summary
Lisocabtagene maraleucel is a CAR T-cell therapy for treatment resistant or more severe B-cell lymphomas.
- Brand Names
- Breyanzi
- Generic Name
- Lisocabtagene maraleucel
- DrugBank Accession Number
- DB16582
- Background
Lisocabtagene maraleucel is a chimeric antigen receptor (CAR) T-cell therapy, similar to brexucabtagene autoleucel and axicabtagene ciloleucel.8,10 Lisocabtagene maraleucel is a genetically modified autologous T-cell therapy that targets CD19, the B-lymphocyte surface antigen B4.10
CAR T-cell therapy has changed the treatment of B-cell lymphomas, significantly increasing survival rates over standard therapy.8 However, data on the efficacy of CAR T-cell therapies on less severe forms of B-cell lymphoma are lacking.8 Despite the adverse reactions, the majority of patients given lisocabtagene maraleucel reported an overall increase in quality of life over a 1 year period.8
Lisocabtagene maraleucel was granted FDA approval on 5 February 2021 9 and EC approval on 5 April 2022.12 It was later granted Health Canada approval on 6 May 2022.13
- Type
- Biotech
- Groups
- Approved
- Biologic Classification
- Cell transplant therapies
Autologous cell transplant - Synonyms
- liso-cel
- Lisocabtagene maraleucel
- External IDs
- JCAR-017
- JCAR017
Pharmacology
- Indication
Lisocabtagene maraleucel is indicated to treat adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who meet one of the following criteria:10,11
- refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy
- refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age
- relapsed or refractory disease after 2 or more lines of systemic therapy
It is also indicated in several other cancers, including in:10
- adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received ≥2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor
- adult patients with relapsed or refractory follicular lymphoma (FL) who have received 2 or more prior lines of systemic therapy
- adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least 2 prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Refractory chronic lymphocytic leukemia (cll) •••••••••••• ••••• •••••••••• ••••••• •••• • •••••• •••••••• • ••••••• •••••••••• •• ••••• ••• ••••• •••••••• •••••••••• •••••••••• ••••••• •••• • •••••• •••••••• •••••• ••••• ••••••••• •••••••••• Treatment of Refractory diffuse large b cell lymphoma •••••••••••• ••••• ••••• •• ••••• •• •••••••• ••••••• •••••••••• Treatment of Refractory follicular lymphoma •••••••••••• ••••• •• ••••• ••• ••••• •••••••• ••••••••• •••••••••• Treatment of Refractory grade 3b follicular lymphoma •••••••••••• ••••• •••••••••• Treatment of Refractory large b-cell lymphoma •••••••••••• ••••• ••••• •• ••••• •• •••••••• ••••••• •••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Lisocabtagene maraleucel is a CAR T-cell therapy indicated to treat adults with relapsed or refractory large B-cell lymphoma after ≥2 systemic therapies, diffuse large B-cell lymphoma, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and grade 3B follicular lymphoma.10 It has a long duration of action as it is detected in patients up to a year after infusion.10 Patients should be counselled regarding the risk of cytokine release syndrome, false-positive HIV tests, effects on their ability to drive, hypersensitivity, infection, cytopenia, hyogammaglobulinemia, and secondary malignancies.10
- Mechanism of action
Lisocabtagene maraleucel is chimeric antigen receptor (CAR) T-cell therapy that targets CD19, also known as the B-lymphocyte surface antigen B4.10 The CAR is composed of an FMC63 monoclonal antibody single chain variable fragment, IgG4 hinge region, CD28 transmembrane domain, 4-1BB costimulatory domain, and CD3ζ activation domain.10 FMC63 is an IgG2a mouse monoclonal antibody that targets CD19.1 The IgG4 hinge region can interact with Fcγ receptors to modulate the response of hematopoietic cells.2,3 The CD28 transmembrane domain can stimulate the activity or tolerance of T-cells.4 4-1BB enhances cytotoxic T-cell activity as well as the production of interferon-γ.5 The CD23ζ cytoplasmic domain mediates T-cell activation by CD2, a T-cell surface adhesion molecule.6
Target Actions Organism AB-lymphocyte antigen CD19 binderHumans - Absorption
Lisocabtagene maraleucel reaches a median Cmax of 23928.2 copies/µg with a median AUC of 213730 copies*day/µg.7 The median time to peak expansion of T-cells was 12 days.7,10
Compared to non-responders, patients with a partial or complete response showed a 3.55-fold increase in Cmax and a 2.72-fold increase in AUC.7 Compared to non-responders, patients with a higher baseline tumor burden showed a 2.46-fold increase in Cmax, patients with cytokine release syndrome showed a 2.29-fold increase, and patients with neurological events showed a 3.34-fold increase.7
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Data regarding overdoses of lisocabtagene maraleucel are not readily available.10 Patients experiencing an overdose may be experience and increased risk and severity of severe infections, severe and prolonged cytopenia, hypogammaglobulinemia, cytokine release syndrome, and neurological toxicities.10 In the event of an overdose, initiate symptomatic and supportive measures.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- 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 Lisocabtagene maraleucel is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Lisocabtagene maraleucel is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Lisocabtagene maraleucel is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Lisocabtagene maraleucel is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when Lisocabtagene maraleucel 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.
- International/Other Brands
- Breyanzi (Bristol Myers Squibb)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Breyanzi 35550000 cells/ml Intravenous Bristol Myers Squibb Pharma Eeig 2022-05-04 Not applicable EU Breyanzi Suspension 120000000 cells Intravenous Bristol Myers Squibb Not applicable Not applicable Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Breyanzi Lisocabtagene maraleucel (50000000 1/5mL) + Lisocabtagene maraleucel (50000000 1/5mL) Injection, suspension; Kit Intravenous Juno Therapeutics, Inc. 2021-02-05 Not applicable US Breyanzi Lisocabtagene maraleucel (50000000 1/5mL) + Lisocabtagene maraleucel (50000000 1/5mL) Injection, suspension; Kit Intravenous Juno Therapeutics, Inc. 2021-02-05 Not applicable US
Categories
- ATC Codes
- L01XL08 — Lisocabtagene maraleucel
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 7K2YOJ14X0
- CAS number
- Not Available
References
- General References
- Zola H, MacArdle PJ, Bradford T, Weedon H, Yasui H, Kurosawa Y: Preparation and characterization of a chimeric CD19 monoclonal antibody. Immunol Cell Biol. 1991 Dec;69 ( Pt 6):411-22. doi: 10.1038/icb.1991.58. [Article]
- Davies AM, Sutton BJ: Human IgG4: a structural perspective. Immunol Rev. 2015 Nov;268(1):139-59. doi: 10.1111/imr.12349. [Article]
- Nimmerjahn F, Ravetch JV: Fcgamma receptors as regulators of immune responses. Nat Rev Immunol. 2008 Jan;8(1):34-47. doi: 10.1038/nri2206. [Article]
- Leddon SA, Fettis MM, Abramo K, Kelly R, Oleksyn D, Miller J: The CD28 Transmembrane Domain Contains an Essential Dimerization Motif. Front Immunol. 2020 Jul 16;11:1519. doi: 10.3389/fimmu.2020.01519. eCollection 2020. [Article]
- Vinay DS, Kwon BS: 4-1BB (CD137), an inducible costimulatory receptor, as a specific target for cancer therapy. BMB Rep. 2014 Mar;47(3):122-9. doi: 10.5483/bmbrep.2014.47.3.283. [Article]
- Howard FD, Moingeon P, Moebius U, McConkey DJ, Yandava B, Gennert TE, Reinherz EL: The CD3 zeta cytoplasmic domain mediates CD2-induced T cell activation. J Exp Med. 1992 Jul 1;176(1):139-45. doi: 10.1084/jem.176.1.139. [Article]
- Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, Mehta A, Purev E, Maloney DG, Andreadis C, Sehgal A, Solomon SR, Ghosh N, Albertson TM, Garcia J, Kostic A, Mallaney M, Ogasawara K, Newhall K, Kim Y, Li D, Siddiqi T: Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020 Sep 19;396(10254):839-852. doi: 10.1016/S0140-6736(20)31366-0. Epub 2020 Sep 1. [Article]
- Vitale C, Strati P: CAR T-Cell Therapy for B-Cell non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia: Clinical Trials and Real-World Experiences. Front Oncol. 2020 May 27;10:849. doi: 10.3389/fonc.2020.00849. eCollection 2020. [Article]
- FDA Press Announcements: FDA approves lisocabtagene maraleucel for relapsed or refractory large B-cell lymphoma [Link]
- FDA Approved Drug Products: Breyanzi (Lisocabtagene Maraleucel) Intravenous Infusion [Link]
- EMA Approved Drug Products: Breyanzi (lisocabtagene maraleucel) intravenous infusion [Link]
- Bristol Myers Squibb News: Bristol Myers Squibb Receives European Commission Approval for CAR T Cell Therapy Breyanzi (lisocabtagene maraleucel) for Certain Forms of Relapsed or Refractory Large B-cell Lymphoma [Link]
- Health Canada Approved Drug Products: BREYANZI (lisocabtagene maraleucel) Intravenous Infusion [Link]
- External Links
- 2479136
- Wikipedia
- Lisocabtagene_maraleucel
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Not Available Acute Lymphoblastic Leukemia (ALL) / Large B Cell Lymphoma 1 somestatus stop reason just information to hide Not Available Available Not Available Diffuse Large B-Cell Lymphoma (DLBCL) 1 somestatus stop reason just information to hide Not Available Recruiting Not Available Chronic Lymphocytic Leukemia / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL) 1 somestatus stop reason just information to hide 3 Not Yet Recruiting Treatment Relapsed or Refractory Follicular Lymphoma 1 somestatus stop reason just information to hide 3 Withdrawn Treatment B-Cell Chronic Lymphocytic Leukemia 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, suspension; kit Intravenous Suspension Intravenous 120000000 cells - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- Curator comments
- Binding to CD19 induces the activity of the CAR T-cell to lyse the targeted cell.
- General Function
- Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B-cell responses to antigens (PubMed:1373518, PubMed:16672701, PubMed:2463100). Activates signaling pathways that lead to the activation of phosphatidylinositol 3-kinase and the mobilization of intracellular Ca(2+) stores (PubMed:12387743, PubMed:16672701, PubMed:9317126, PubMed:9382888). Is not required for early steps during B cell differentiation in the blood marrow (PubMed:9317126). Required for normal differentiation of B-1 cells (By similarity). Required for normal B cell differentiation and proliferation in response to antigen challenges (PubMed:1373518, PubMed:2463100). Required for normal levels of serum immunoglobulins, and for production of high-affinity antibodies in response to antigen challenge (PubMed:12387743, PubMed:16672701, PubMed:9317126)
- Specific Function
- Not Available
- Gene Name
- CD19
- Uniprot ID
- P15391
- Uniprot Name
- B-lymphocyte antigen CD19
- Molecular Weight
- 61127.985 Da
References
- FDA Approved Drug Products: Breyanzi (Lisocabtagene Maraleucel) Intravenous Infusion [Link]
Drug created at February 09, 2021 22:44 / Updated at October 11, 2024 22:08