Identification
- Summary
Ciltacabtagene autoleucel is a BCMA-directed CAR T-cell therapy used in the treatment of relapsed or refractory multiple myeloma in previously treated patients.
- Brand Names
- Carvykti
- Generic Name
- Ciltacabtagene autoleucel
- DrugBank Accession Number
- DB16738
- Background
Multiple myeloma is a malignancy involving the plasma cells of the bone marrow. It is a rare malignancy, with an estimated yearly incidence of 6.5 people per 100,000,4 and is variable in its presentation - some patients may remain entirely asymptomatic, while others may experience a range of symptoms including bone pain, hematologic abnormalities, and end-organ damage.4 There have been a number of treatments developed for multiple myeloma (e.g. daratumumab), although none are curative.1
B-cell maturation antigen (BCMA) is a transmembrane glycoprotein member of the tumor necrosis factor receptor superfamily 17 (TNFRSF17) which is used as a biomarker for multiple myeloma.1 While normally expressed on plasma blasts and plasma cells, BCMA is widely expressed on malignant plasma cells and most multiple myeloma cell lines, making it a choice target in the development of immunotherapies against multiple myeloma.1
Ciltacabtagene autoleucel (Carvykti, Jannsen Biotech Inc.) is a BCMA-directed genetically modified autologous T-cell immunotherapy.2 Patient T-cells are reprogrammed with a transgene encoding a specific chimeric antigen receptor (CAR) which features two BCMA-targeting single-domain antibodies.2 Re-infusion of these modified T-cells leads to the targeted elimination of malignant plasma cells, on which BCMA is highly expressed.1 Carvykti was first approved by the FDA in February 2022 for the treatment of relapsed or refractory multiple myeloma in treatment-experienced patients.3
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Cell transplant therapies
Autologous cell transplant - Synonyms
- Autologous bi-epitope BCMA-targeted CAR T-cells
- Ciltacabtagene autoleucel
- External IDs
- JNJ-68284528
- LCAR-B38M CAR-T cells
Pharmacology
- Indication
Ciltacabtagene autoleucel is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma after ≥4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.2
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 multiple myeloma •••••••••••• ••••• •••••••• •••••••••••••••• ••••• •••••••••• •••••••• •••••••••• ••••••••• •••••••••• •••••••• ••••••••• •••••••••• •••••••• ••••••••• •••••••••• •••••••••• Treatment of Relapsed multiple myeloma •••••••••••• ••••• •••••••• •••••••••••••••• ••••• •••••••••• •••••••• •••••••••• ••••••••• •••••••••• •••••••• ••••••••• •••••••••• •••••••• ••••••••• •••••••••• •••••••••• - Contraindications & Blackbox Warnings
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Treatment with ciltacabtagene autoleucel comprises a single infusion of a dose range between 0.5-1.0x106 CAR-positive viable T-cells per kilogram of body weight.2
Patients receiving treatment with ciltacabtagene autoleucel are required to undergo monitoring through a Risk Evaluation and Mitigation Strategy (REMS) called the Carvykti REMS.2 There are a number of potentially serious adverse reactions related to ciltacabtagene autoleucel therapy which require close monitoring and intervention. Cytokine Release Syndrome (CRS), which may be fatal, may be mitigated with the use of tocilizumab and/or corticosteroids.2 Similarly, significant neurologic toxicities (including Immune Effector Cell-Associated Neurotoxicity Syndrome [ICANS]) may occur and can be treated with supportive care and/or corticosteroid therapy as required.2 Serious hematologic adverse effects - including hemophagocytic lymphohistiocytosis (HLH), macrophage activation syndrome (MAS), and various recurrent/prolonged cytopenias - have also been observed in patients following treatment with ciltacabtagene autoleucel.2
- Mechanism of action
Ciltacabtagene autoleucel is a chimeric antigen receptor (CAR) T-cell therapy in which genetically modified autologous T-cells are reprogrammed to target B-cell maturation antigen (BCMA), a biomarker of multiple myeloma.2 Patient peripheral blood mononuclear cells are obtained via leukapheresis, after which they are enriched for T-cells and genetically modified ex vivo to express a CAR comprising an anti-BCMA targeting domain consisting of two single-domain anti-BCMA antibodies linked to a 4-1BB costimulatory domain and a CD3-zeta signaling domain.2
The genetically modified CAR T-cells are then expanded, washed, and cryopreserved for shipping back to the patient. When the product is infused back into the patient, the anti-BCMA CAR T-cells are able to recognize and eliminate BCMA-expressing target cells, including malignant plasma cells involved in multiple myeloma.2
Target Actions Organism ATumor necrosis factor receptor superfamily member 17 binderHumans - Absorption
Following a single infusion of a median dose of 0.71x106 CAR positive viable T cells/kg, the median Cmax and AUC0-28d were 47806 copies/µg genomic DNA and 371569 copies*day/µg genomic DNA.2 The median Tmax was 12.7 days.2
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
The median half-life of ciltacabtagene autoleucel following a single infusion of a median dose of 0.71x106 CAR positive viable T cells/kg was 15.3 days.2
- 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
Not Available
- 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 Ciltacabtagene autoleucel is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Ciltacabtagene autoleucel is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Ciltacabtagene autoleucel is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Ciltacabtagene autoleucel is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when Ciltacabtagene autoleucel is combined with Bupivacaine. - Food Interactions
- Not Available
Products
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- Carvykti (Janssen Biotech, Inc.)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Carvykti Suspension 100000000 cells / bag Intravenous Janssen Pharmaceuticals Not applicable Not applicable Canada 
Carvykti Injection, suspension 100000000 1/1 Intravenous Janssen Biotech, Inc 2022-02-28 Not applicable US 
Carvykti Injection 51600000 cells Intravenous Janssen Cilag International Nv 2022-06-21 Not applicable EU 
Categories
- ATC Codes
- L01XL05 — Ciltacabtagene autoleucel
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Humans
Chemical Identifiers
- UNII
- 0L1F17908Q
- CAS number
- Not Available
References
- General References
- Nobari ST, Nojadeh JN, Talebi M: B-cell maturation antigen targeting strategies in multiple myeloma treatment, advantages and disadvantages. J Transl Med. 2022 Feb 10;20(1):82. doi: 10.1186/s12967-022-03285-y. [Article]
- FDA Approved Drug Products: Carvykti (ciltacabtagene autoleucel) suspension for intravenous infusion [Link]
- Johnson & Johnson: U.S. FDA Approves CARVYKTI™ (ciltacabtagene autoleucel), Janssen’s First Cell Therapy, a BCMA-Directed CAR-T Immunotherapy for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma [Link]
- National Organization for Rare Disorders: Multiple Myeloma [Link]
- External Links
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Recruiting Other Multiple Myeloma (MM) 1 3 Active Not Recruiting Treatment Multiple Myeloma (MM) 1 3 Recruiting Treatment Multiple Myeloma (MM) 2 2 Active Not Recruiting Treatment Multiple Myeloma (MM) 1 2 Completed Treatment Multiple Myeloma (MM) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 51600000 cells Injection, suspension Intravenous 100000000 1/1 Suspension Intravenous 100000000 cells / bag - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- Receptor for TNFSF13B/BLyS/BAFF and TNFSF13/APRIL. Promotes B-cell survival and plays a role in the regulation of humoral immunity. Activates NF-kappa-B and JNK.
- Specific Function
- Signaling receptor activity
- Gene Name
- TNFRSF17
- Uniprot ID
- Q02223
- Uniprot Name
- Tumor necrosis factor receptor superfamily member 17
- Molecular Weight
- 20165.065 Da
References
- FDA Approved Drug Products: Carvykti (ciltacabtagene autoleucel) suspension for intravenous infusion [Link]
Drug created at November 03, 2021 15:06 / Updated at March 05, 2022 01:02