Carvykti

What is Carvykti?

Carvykti (ciltacabtagene autoleucel) is a personalized CAR T-cell therapy used to treat relapsed or refractory multiple myeloma (RRMM). It is used in adults whose multiple myeloma has returned or stopped responding to earlier treatments and may be used as early as the first relapse in certain patients.

Carvykti is a one-time infusion using a patient’s own genetically modified T cells to recognize and destroy multiple myeloma cells that express the BCMA protein.

For Carvykti treatment, T cells (a type of white blood cell) are collected from your blood and modified at the manufacturing site. A specialized receptor, called a chimeric antigen receptor (CAR), is added to the surface of the T cells. This enables it to recognize and attack multiple myeloma cells that carry the BCMA protein.

Once modified, the T cells are multiplied and infused back into your body as a personalized immunotherapy. After infusion, these CAR-T cells can seek out and kill BCMA-expressing multiple myeloma cells, helping improve disease control and clinical outcomes.

Carvykti is a BCMA-targeted CAR-T cell therapy.

Who Is Eligible for Carvykti Therapy?

Carvykti is FDA approved for the treatment of adults with relapsed or refractory multiple myeloma who meet all of the following criteria:

• Have multiple myeloma that has returned or stopped responding to treatment
• Have received at least one prior line of therapy
• Have been treated with:
  • A proteasome inhibitor, and
  • An immunomodulatory agent
• Have disease that is refractory to lenalidomide (no longer responds to lenalidomide treatment)

Carvykti may be used as early as the first relapse in appropriate patients when previous therapies have not been effective.

What is the Carvykti treatment process?

The Carvykti CAR T-cell therapy process is:

• T-cell collection: T cells, a type of white blood cell, are collected from your blood through a process called leukapheresis.
• Genetic modification: At a specialized manufacturing facility, a chimeric antigen receptor (CAR) is added to the surface of the T cells.
• Targeting BCMA: This CAR enables the T cells to recognize BCMA (B-cell maturation antigen), a protein found on multiple myeloma cells.
• Cell expansion: The modified CAR T cells are multiplied in the laboratory to create a sufficient number of cells for treatment.
• One-time infusion: The modified T cells are infused back into your body as a personalized immunotherapy.
• Cancer cell attack: After infusion, the CAR-T cells seek out and kill BCMA-expressing multiple myeloma cells, helping improve disease control and clinical outcomes.

How effective is Carvykti for RRMM?

New data from the Phase 3 CARTITUDE-4 study (NCT04181827) demonstrated that Carvykti was more effective than standard therapy.

• At 12 months, the estimated progression-free survival (PFS) rate was 75.9% with Carvykti compared to 49.5% with standard therapy. 
• In addition, 74.0% of patients treated with Carvykti achieved a complete response or better, while only 22.3% of patients on standard therapy reached that level of response. 
• An update to this study at a median follow-up of 33.6 months reported a statistically significant improvement in the overall survival rate with Carvykti compared to standard therapy.

These response rates were assessed by an Independent Review Committee (IRC) using the International Myeloma Working Group (IMWG) criteria.

Boxed Warnings

Carvykti has boxed warnings for cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), Parkinsonism and Guillain-Barré syndrome (GBS), hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), prolonged and/or recurrent cytopenias, immune-effector cell-associated enterocolitis (IEC-EC), and secondary hematological malignancies. 

A boxed warning is the strongest safety-related warning issued by the FDA. 

• Cytokine Release Syndrome (CRS). This includes fatal or life-threatening reactions, that have occurred in patients following treatment with Carvykti. Do not administer this medicine to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
• Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). This may be fatal or life-threatening, and has occurred following treatment with Carvykti, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with Carvykti .  Supportive care and/or corticosteroids should be provided as needed.
• Parkinsonism and Guillain-Barré syndrome and their associated complications have occurred following Carvykti treatment resulting in fatal or life-threatening reactions.
• Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), including fatal and life-threatening reactions, have occurred in patients following treatment with this medicine. HLH/MAS can occur with CRS or neurologic toxicities.
• Prolonged or recurrent cytopenias (low blood cell counts) have occurred after treatment with Carvykti and may be associated with bleeding, infection, and the need for stem cell transplantation to restore blood cell production.
• Immune Effector Cell–associated enterocolitis (IEC-EC), including fatal or life-threatening reactions, has been reported following treatment with Carvykti.
• Secondary blood cancers, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), have occurred after treatment with Carvykti. T-cell malignancies have also been reported following treatment of blood cancers with BCMA- and CD19-directed genetically modified autologous T-cell therapies, including Carvykti. 

Warnings and Precautions

• Prolonged and Recurrent Cytopenias: Cytopenia is low levels of red blood cells (anemia), white blood cells (leukopenia) or platelets (thrombocytopenia). Cytopenia may occur after Carvykti infusion. Prolonged neutropenia has been associated with increased risk of infection. Blood counts should be monitored before and after the infusion.
• Infections: Patients should be monitored for signs and symptoms of infection and receive appropriate treament if necessary.
• Hypogammaglobulinemia (low levels of immunoglobulins):  Your immunoglobulin levels will be monitored and immunoglobulin replacement therapy may be considered if required.
• Hypersensitivity Reactions: Hypersensitivity reactions have occurred. Monitor for hypersensitivity reactions during infusion. ( 5.8)
• Secondary Malignancies: Secondary hematological malignancies, including myelodysplastic syndrome and acute myeloid leukemia, have occurred. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including this medicine. Contact Janssen Biotech, Inc. at 1-800-526-7736, if this occurs.
• Immune-effector cell-associated enterocolitis (IEC-EC): Carvykti can cause serious gastrointestinal side effects, including severe or persistent diarrhea or ruptured bowel, which can be life-threatening and may lead to death. Tell your healthcare provider right away if you develop diarrhea, abdominal pain, weight loss, fever, chills, or any signs or symptoms of an infection. 

Differences in survival rates in the first 10 months were found in a study comparing Carvykti to standard therapy.

• 14% in the Carvykti arm died compared to 12% in the standard therapy arm.
• The increased death rate occurred before and after receiving Carvykti treatment.
• The reasons for death were progression of multiple myeloma and side effects of the treatment. 

However, the FDA has determined that the overall benefit of Carvykti continues to outweigh the potential risks. 

Carvykti side effects

Carvykti common side effects

Carvykti Common side effects may include:

• confusion, cough, trouble breathing, fast or irregular heartbeats, feeling light-headed or very tired;
• headache, dizziness;
• problems with speech;
• low blood cell counts;
• fever, chills, tiredness, or other signs of infection;
• decreased appetite, constipation, nausea, or diarrhea; or
• pain in your joints or muscles.

Serious side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

A serious side effect of Carvykti is called cytokine release syndrome (CRS). Tell your caregivers right away if you have signs of this condition: fever, chills, trouble breathing, severe vomiting or diarrhea, tremors, shaking, fast or irregular heartbeats, feeling light-headed, or feeling very tired. Your caregivers will have medication available to quickly treat CRS if it occurs.

Also, call your doctor at once if you have:

• confusion, loss of consciousness, seizures, problems with speech, reading, or writing, depression
• personality changes, including a reduced ability to express emotions, being less talkative,
  disinterest in activities, and reduced facial expression
• tingling and numbness of hands and feet, leg and arm weakness, facial numbness; or
• low blood cell counts – fever, chills, tiredness, flu-like symptoms, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath
• persistent or severe diarrhea, abdominal pain, and weight loss.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects.

Before taking this medicine

Tell your doctor if you have ever had:

• neurologic problems (such as stroke, seizures, memory loss);
• breathing problems;
• heart problems;
• liver or kidney disease;
• diarrhea;
• recent or active infection; or
• low blood counts.

Pregnancy

Carvykti is not recommended for women who are pregnant or for women of childbearing potential not using contraception. Pregnant women should be advised that there may be risks to the fetus. Pregnancy after this therapy should be discussed with the treating physician.

Women will need pregnancy testing before receiving this medicine. You will also need to use birth control to prevent pregnancy during treatment with this medicine. Tell your doctor if you are pregnant or plan to become pregnant.

Breastfeeding

It may not be safe to breastfeed while using this medicine. Ask your doctor about any risks.

How should I receive Carvykti?

The Carvykti treatment process involves:

1. T-cell collection – A patient’s white blood cells (T cells) are collected via leukapheresis.
2. Genetic modification – The T cells are engineered to express a CAR that recognizes BCMA, a protein highly expressed on multiple myeloma cells.
3. Expansion and conditioning – The modified T cells are multiplied in a lab, while the patient undergoes lymphodepleting chemotherapy to prepare for infusion.
4. One-time infusion – The patient receives an intravenous (IV) infusion of Carvykti.
5. Post-treatment monitoring – Patients are closely monitored for cytokine release syndrome (CRS) and other potential side effects.

Dosing information

Recommended dose: 0.5-1.0×10⁶ CAR-positive viable T cells per kg, with a maximum dose of 1×10⁸ CAR-positive viable T cells per infusion.

Pre-medication required: Acetaminophen and an H1-antihistamine before infusion.

General dosing information:

• Administered intravenously at an authorized facility.
• Patients should stay within 2 hours of the treatment facility for at least 4 weeks post-infusion for monitoring.

What should I avoid after receiving this medicine?

• Do not drive, operate heavy machinery, or do other activities that could be dangerous if you are not mentally alert for at least 8 weeks after you get Carvykti. This is because the treatment can cause memory and coordination problems, sleepiness, confusion, dizziness, seizures, or other neurologic side effects, as discussed by your healthcare provider.
• You must not be given certain vaccines called live vaccines for some time before and after Carvykti treatment. Talk to your healthcare provider if you need to have any vaccinations.
• Do not donate blood, organs, tissues, or cells for transplantation.

What other drugs will affect Carvykti?

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Some commercial Human Immunodeficiency Virus (HIV) tests may incorrectly give you an HIV-positive result while you are receiving treatment with Carvykti.

Carvykti Package Insert

HCPs and patients often use the Carvykti Package Insert (PI) for more detailed information about this medicine. The Carvykti Package Insert contains more detailed information on Indications and Usage, Dosage and Administration, Clinical Pharmacology, Clinical Studies, Drug Interaction, and more. Discuss any medical questions you have with your doctor or other health care provider. This is not all the information you need to know about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

The Package Insert is sometimes called the FDA label, or Carvykti Prescribing Information (PI).

Ingredients

Active ingredient: ciltacabtagene autoleucel

Inactive ingredients: DMSO

Manufacturer Information

Carvykti Manufacturer Janssen Biotech, Inc., Horsham, PA, USA.

Marketing Partner Legend Biotech, Somerset, NJ, USA.

Carvykti Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There is 1 for Carvykti.Carvykti (ciltacabtagene autoleucel) – Janssen Biotech, Inc.

Formulation type	Strength
Bag	0.5 to 1.0×10^6 chimeric antigen receptor (CAR)-positive viable T cells per kg of body weight, with a maximum dose of 1×10^8 CAR-positive viable T cells in one infusion