Ciltacabtagene autoleucel (Carvykti) Uses, Dose, MOA, Side effects

Ciltacabtagene autoleucel, sold under the brand name Carvykti by Janssen Pharmaceutical companies, is a type of cancer treatment known as a chimeric antigen receptor (CAR) T-cell therapy.

It is used to treat certain types of cancer, specifically relapsed or refractory mantle cell lymphoma (MCL) in adults.

CAR T-cell therapy involves extracting T-cells (a type of immune cell) from a patient’s blood, genetically modifying them in a laboratory to produce special receptors called CARs that can recognize and attack cancer cells, and then infusing the modified cells back into the patient’s bloodstream.

The modified T-cells can then target and kill cancer cells that express a specific protein on their surface, such as CD19 or CD22.

Ciltacabtagene autoleucel specifically targets CD19-expressing cells and has been shown to be effective in clinical trials for the treatment of relapsed or refractory mantle cell lymphoma in adults.

However, it can also cause serious side effects, including cytokine release syndrome, which is a potentially life-threatening immune reaction.

Ciltacabtagene autoleucel (Carvykti) FDA-Approved Indications:

Ciltacabtagene autoleucel (Carvykti) has been approved for the treatment of the following cancers:

• The treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least one prior line of therapy.
• The treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy, 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.

On 28th February 2022, the FDA approved Ciltacabtagene autoleucel (Carvykti) for the treatment of refractory multiple myeloma who have not responded to at least four FDA-approved treatments of multiple myeloma including [Ref]:

• a proteasome inhibitor (Bortezomib)
• an immunomodulatory agent, and
• anti-CD38 monoclonal antibody

Ciltacabtagene autoleucel (Carvykti) Dose:

The recommended dose of Carvykti is as follows:

For the treatment of relapsed or refractory MCL:

• A single infusion of Carvykti at a target dose of 0.75 to 1.0 x 10^6 CAR-positive viable T cells per kilogram of body weight, up to a maximum of 2 x 10^8 CAR-positive viable T cells.

For the treatment of relapsed or refractory LBCL:

• A single infusion of Carvykti at a target dose of 0.5 to 1.0 x 10^6 CAR-positive viable T cells per kilogram of body weight, up to a maximum of 2.0 x 10^8 CAR-positive viable T cells.

For the treatment of relapsed or refractory multiple myeloma [Ref]:

• A single infusion of Carvykti at a target dose of 0.5 to 1.0 x 10^6 CAR-positive viable T cells per kilogram of body weight, up to a maximum of 1.0 x 10^8 CAR-positive viable T cells.

It is important to start Carvykti treatment 2 to 4 days after a lymphocyte-depleting regimen. Patients may need to be premedicated before the infusion.

How to pre-medicate before Carvykti infusion?

1. Antipyretics: acetaminophen and/or non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, to help reduce fever and flu-like symptoms.
2. Antihistamines: diphenhydramine or other H1 receptor antagonists, to help reduce the risk of allergic reactions.
3. Corticosteroids: dexamethasone or other corticosteroids, to help reduce the risk of infusion-related reactions and CRS.
4. Prophylactic antibiotics: such as sulfamethoxazole/trimethoprim or fluoroquinolones, to help reduce the risk of bacterial infections.
5. Intravenous (IV) fluids: to help prevent dehydration and support the patient’s blood pressure during and after the infusion.

Ciltacabtagene autoleucel (Carvykti) has not been studied in pregnant women, children, and advanced kidney and liver disease.

Ciltacabtagene autoleucel (Carvykti) Contraindications:

The prescribing information for Ciltacabtagene autoleucel (Carvykti) lists the following contraindications:

• Patients with a history of severe hypersensitivity reaction to the active substance (Ciltacabtagene autoleucel) or any of the excipients.
• Patients with an active systemic infection.
• Patients with a history of progressive multifocal leukoencephalopathy (PML).
• Patients with active central nervous system (CNS) involvement by malignancy.
• Patients with a history of allogeneic hematopoietic stem cell transplant (HSCT).
• Patients with a known history of the human immunodeficiency virus (HIV) or active hepatitis B or C infection.

Ciltacabtagene autoleucel (Carvykti Side effects:

Ciltacabtagene autoleucel (Carvykti) Mechanism of action (MOA):

Ciltacabtagene autoleucel (Carvykti) is a chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy involves the genetic modification of a patient’s own T-cells to express a CAR that recognizes and binds to a specific antigen on the surface of cancer cells.

Once the CAR T-cells are infused back into the patient, they multiply and attack the cancer cells expressing the target antigen.

The CAR construct used in Carvykti targets the CD19 antigen, which is expressed on the surface of B-cells, including malignant B-cells in certain hematologic malignancies such as mantle cell lymphoma (MCL), large B-cell lymphoma (LBCL), and Multiple Myeloma.

The CAR consists of an extracellular domain that recognizes CD19, a transmembrane domain, and an intracellular domain that activates the T-cell signaling pathway, leading to the destruction of CD19-expressing cancer cells.

In summary, Carvykti works by genetically modifying a patient’s own T-cells to express a CAR that recognizes and binds to the CD19 antigen on the surface of cancer cells, leading to the destruction of CD19-expressing cancer cells.

How costly is Ciltacabtagene autoleucel (Carvykti)?

The cost of Ciltacabtagene autoleucel (Carvykti) varies depending on several factors such as the patient’s insurance coverage, the specific treatment regimen, and the healthcare provider administering the therapy.

However, as of February 2023, the list price for Carvykti in the United States is approximately $400,000 for a single treatment course.

In Conclusion:

As a relatively new gene therapy, there are still several aspects of Ciltacabtagene autoleucel (Carvykti) that are less known or still being studied. Some of these include:

The long-term durability of response:

• While Carvykti has demonstrated high response rates and durable remissions in some patients with certain hematologic malignancies, it is still unclear how long these responses will last in the long term.

Potential for late effects:

• Due to the nature of CAR T-cell therapy, there is a potential for long-term effects that may not be immediately apparent. Further studies are needed to fully understand the potential long-term effects of Carvykti.

Optimal timing and sequencing of therapy:

• It is still unclear what the optimal timing and sequencing of Carvykti and other treatment modalities may be for certain patients with hematologic malignancies.

Effectiveness in other cancer types:

• While Carvykti has shown promising results in certain hematologic malignancies, it is still being studied for its potential efficacy in other types of cancer.

Overall, while Carvykti represents a promising new treatment option for certain patients with relapsed or refractory hematologic malignancies, there is still much to be learned about its long-term efficacy and safety.