NAV

Lisocabtagene maraleucel

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
Poor quality drug data slowing you down?
Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.
Download eBook
Poor quality drug data slowing you down?
Download eBook

Pharmacology

Indication

Lisocabtagene maraleucel is 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.10,11

Under accelerated approval, it is also indicated to treat adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least two prior lines of therapy including, a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor.10

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofGrade 3b follicular lymphoma•••••••••••••••••••••••••••
Treatment ofHigh-grade b-cell lymphoma•••••••••••••••••••••••••••
Treatment ofPrimary mediastinal large b-cell lymphomas•••••••••••••••••••••••••••
Treatment ofRefractory chronic lymphocytic leukemia (cll)••••••••••••••••••••••••••• ••••••• •••• • •••••• •••••••• • ••••••• •••••••••• •• ••••• ••• ••••• •••••••• •••••••••• •••••••••• ••••••• •••• • •••••• •••••••• •••••• ••••• •••••••••
Treatment ofRefractory diffuse large b cell lymphoma•••••••••••••••••••••• •• ••••• •• •••••••• •••••••••••••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
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

TargetActionsOrganism
UB-lymphocyte antigen CD19
binder
Humans
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 outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
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.
DrugInteraction
Integrate drug-drug
interactions in your software
AmbroxolThe risk or severity of methemoglobinemia can be increased when Lisocabtagene maraleucel is combined with Ambroxol.
ArticaineThe risk or severity of methemoglobinemia can be increased when Lisocabtagene maraleucel is combined with Articaine.
BenzocaineThe risk or severity of methemoglobinemia can be increased when Lisocabtagene maraleucel is combined with Benzocaine.
Benzyl alcoholThe risk or severity of methemoglobinemia can be increased when Lisocabtagene maraleucel is combined with Benzyl alcohol.
BupivacaineThe 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 regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
International/Other Brands
Breyanzi (Bristol Myers Squibb)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BreyanziSuspension120000000 cellsIntravenousBristol Myers SquibbNot applicableNot applicableCanada flag
Breyanzi35550000 cells/mlIntravenousBristol Myers Squibb Pharma Eeig2022-05-04Not applicableEU flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
BreyanziLisocabtagene maraleucel (50000000 1/5mL) + Lisocabtagene maraleucel (50000000 1/5mL)Injection, suspension; KitIntravenousJuno Therapeutics, Inc.2021-02-05Not applicableUS flag
BreyanziLisocabtagene maraleucel (50000000 1/5mL) + Lisocabtagene maraleucel (50000000 1/5mL)Injection, suspension; KitIntravenousJuno Therapeutics, Inc.2021-02-05Not applicableUS flag

Categories

Drug Categories
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
7K2YOJ14X0
CAS number
Not Available

References

General References
  1. 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]
  2. Davies AM, Sutton BJ: Human IgG4: a structural perspective. Immunol Rev. 2015 Nov;268(1):139-59. doi: 10.1111/imr.12349. [Article]
  3. 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]
  4. 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]
  5. 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]
  6. 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]
  7. 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]
  8. 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]
  9. FDA Press Announcements: FDA approves lisocabtagene maraleucel for relapsed or refractory large B-cell lymphoma [Link]
  10. FDA Approved Drug Products: Breyanzi (Lisocabtagene Maraleucel) Intravenous Infusion [Link]
  11. EMA Approved Drug Products: Breyanzi (lisocabtagene maraleucel) intravenous infusion [Link]
  12. 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]
  13. Health Canada Approved Drug Products: BREYANZI (lisocabtagene maraleucel) Intravenous Infusion [Link]
RxNav
2479136
Wikipedia
Lisocabtagene_maraleucel

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Not Yet RecruitingTreatmentRelapsed or Refractory Follicular Lymphoma1
3WithdrawnTreatmentB-Cell Chronic Lymphocytic Leukemia1
2Active Not RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentB-Cell Lymphoma / Diffuse Large B-Cell Lymphoma (DLBCL) / Immune System Disorders / Immunoproliferative Disorders / Lymphatic Disorders / Lymphoma / Lymphoproliferative Disorders / Neoplasm / Neoplasms by Histologic Type / Non-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentB-Cell Lymphoma / Diffuse Large B-Cell Lymphoma (DLBCL) / Non-Hodgkin's Lymphoma (NHL)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, suspension; kitIntravenous
SuspensionIntravenous120000000 cells
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Details1. B-lymphocyte antigen CD19
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
Curator comments
Binding to CD19 induces the activity of the CAR T-cell to lyse the targeted cell.
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
References
  1. FDA Approved Drug Products: Breyanzi (Lisocabtagene Maraleucel) Intravenous Infusion [Link]

Drug created at February 09, 2021 22:44 / Updated at April 08, 2024 21:18