Carvykti (ciltacabtagene autoleucel)

What Is Carvykti?

CARVYKTI® (also known as ciltacabtagene autoleucel, the generic drug name) or “cilta-cel” for short. Carvykti was approved by the U.S. Food and Drug Administration (FDA) in February 2022 for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM). 

How Is Carvykti Used in Multiple Myeloma?

The FDA approval of Carvykti in February 2022 was based on data from the phase Ib/II CARTITUDE-1 clinical trial. Early, deep, and durable responses were observed in heavily pretreated patients after a single infusion of Carvykti. Of the 61 patients who were evaluated for minimal residual disease (MRD), 92% were MRD-negative at 10-5. Updated results from this clinical trial demonstrated that responses deepened over time. 

In April 2024, the FDA approved an expanded indication for the use of Carvykti® for the treatment of patients with relapsed / refractory multiple myeloma who have received at least 1 prior line of therapy, including:

• an immunomodulatory agent
• a proteasome inhibitor
• an anti-CD38 monoclonal antibody

Carvykti was previously FDA-approved to be used after at least 4 prior lines of therapy.  

The expanded FDA approval is based on data from the CARTITUDE-4 phase III clinical trial. In the Carvykti arm of the study, progression-free survival (PFS) was not reached at 24 months versus progression-free survival 12 months with Pomalyst® (pomalidomide), Velcade, and dexamethasone [PVd]; or Darzalex, Pomalyst, and dexamethasone [DPd] in patients with relapsed and Revlimid-refractory myeloma who received 1 to 3 prior lines of therapy.  

Carvykti is the first B-cell maturation antigen (BCMA)-targeted therapy approved for the treatment of patients with myeloma as early as first relapse. The new approval makes this important chimeric antigen receptor (CAR) T-cell therapy available to patients earlier in their treatment journey.  

Carvykti continues to be studied in earlier-line treatment settings, including in newly diagnosed myeloma. 

How Does Carvykti Work?

Carvykti is an immunotherapy that enhances the immune system. 

The immune system is our body’s natural defense, designed to:  

• destroy infected and malignant (cancerous) cells
• remove cellular debris

The immune system is very complex. It includes white blood cells (WBC), and organs and tissues of the lymphatic system. Myeloma interferes with the normal function of the immune system. 

Carvykti is a BCMA-directed genetically modified CAR T-cell therapy. Carvykti works by recognizing and binding to BCMA, a protein that is found almost universally on myeloma cells. This leads to the destruction of BCMA-expressing cells, thereby eliminating the myeloma cells. (BCMA is found on healthy cells as well.)  

T cells are a type of WBC that originate in the bone marrow but mature in the thymus, a gland beneath the breastbone (sternum). T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on the cell surface. T cells can recognize specific antigens and bind to them to surround and disable pathogens (infectious agents that cause disease). T cells are one of the most important parts of our immune system. These cells recognize myeloma cells as foreign and cancerous.  

Yet, as myeloma grows, the number of T cells is reduced and their function blocked. As a result, myeloma can continue to grow. T cells are needed to recognize myeloma cells as foreign and destroy them. Each dose of Carvykti is customized using the patient’s T cells that are administered as an intravenous (IV) infusion. 

How is Carvykti Given?

Carvykti is currently administered only at certified treatment centers. Carvykti is delivered as a one-time intravenous infusion. It is manufactured for each individual patient using the patient’s own T cells. The treatment process generally takes 2 to 3 months. 

Steps to Carvykti Treatment 

1. Leukapheresis

Much like collecting stem cells for an autologous transplant, the patient’s own T cells are collected by a procedure called apheresis or leukapheresis. Whole blood is drawn from the patient, then passed through a machine that separates the blood into its individual components. The patient’s white blood cells are collected, and the remaining blood components are then immediately re-infused back into the bloodstream of the patient. This process may take 3 to 6 hours. If more T cells need to be collected, the procedure can be repeated. 

2. Modification and manufacturing of T cells

The white blood cells collected during leukapheresis are sent to a manufacturing facility where T cells are separated out. These T cells are genetically modified to make Carvykti. Then, the Carvykti will recognize and attack BCMA on the surface of the myeloma cells. This is done by inserting a gene into the T cells. This gene insertion makes the T cells express a CAR on the cell surface. It then multiplies the T cells in the lab to manufacture millions of cells. Making  Carvykti CAR-T cells takes approximately 4 to 5 weeks from the time cells are received at the manufacturing laboratory. This timeline may vary.  

3. Pre-infusion chemotherapy

While Carvykti is being made, the patient may receive chemotherapy to treat myeloma so that it doesn’t get worse. Then, for the 3 days prior to infusion of Carvykti, the doctor will give the patient "pre-infusion" chemotherapy to help prepare the body to receive infusion of the genetically modified T cells.  

4. Infusion of Carvykti  

After completing "pre-infusion" chemotherapy, and before receiving Carvykti, the patient may be given medicines to help:

• prevent a potential allergic reaction to Carvykti  
• reduce fever (if any)

The healthcare provider will decide which medicines are best for the patient and will provide proper guidance. 

The patient will then receive a one-time infusion of Carvykti T cells through an intravenous catheter (tube). Due to the specialized nature of T-cell therapy, Carvykti must be administered at a certified treatment center. The infusion lasts approximately 30 to 60 minutes. After the infusion of Carvykti, the genetically modified T cells will begin to seek out myeloma cells and attack them. 

4. Monitoring

After infusion of Carvykti, the doctor will monitor the patient for at least 10 days to observe if the treatment is working, and to check for any signs or symptoms of an adverse reaction which may occur. Blood tests will be used to track progress. The patient must stay close to the center where Carvykti treatment was received for at least 4 weeks. A plan for long-term monitoring and follow-up should be discussed with the patient's doctor.

Carvykti and Its Effects on Ability to Drive and Operate Machinery

For at least 8 weeks following Carvykti infusion, the patient may be at risk for:

• temporary memory and coordination problems 
• sleepiness 
• confusion 
• dizziness 
• seizures

Patients should not drive, operate heavy machinery, or engage in any activities that could be dangerous or hazardous if not mentally alert.  

Warnings and Precautions for Myeloma Patients Undergoing Carvykti Treatment

HIV testing and Carvykti use

Having Carvykti in the blood may cause some commercial tests for the human immunodeficiency virus (HIV) to give a false-positive result, even when the patient may be HIV-negative. 

Risk Evaluation and Mitigation Strategy (REMS) 

The FDA requires a Risk Evaluation and Mitigation Strategy (REMS) program if a specific drug or treatment has serious safety concerns. REMS programs support the use of such drugs or treatments and help ensure that the potential benefits outweigh the risks. The FDA has determined that a REMS program is necessary with Carvykti. Therefore, Carvykti is available only through the CARVYKTI REMS program. Visit carvyktirems.com or call 1.844.672.0067 for more information.  

Cytokine release syndrome (CRS)

Cytokines are proteins secreted by cells that can stimulate or inhibit growth/activity in other cells. In patients with myeloma, cytokines are produced in the bone marrow and circulate in the bloodstream. Cytokines are normally released in response to infection.  

Cytokine release syndrome (CRS) is a potentially fatal, uncontrolled immune reaction in which cytokines become highly elevated and trigger an overwhelming immune system response. A “cytokine storm” can seriously damage body tissues and organs.  

CRS has occurred in some patients following treatment with Carvykti in clinical trials, including severe, life-threatening, or fatal reactions. Symptoms of CRS include the following:

• fever 
• difficulty breathing 
• dizziness or lightheadedness 
• nausea 
• headache 
• tachycardia (fast heartbeat) 
• low blood pressure 
• fatigue 

Severe or life-threatening CRS is treated with tocilizumab or tocilizumab together with steroids. It is important to promptly alert the doctor if there is any change in the patient's health or if the patient is not feeling well while receiving treatment with Carvykti. 

Neurologic toxicities 

Immune effector cell-associated neurotoxicity syndrome (ICANS) has occurred in patients following treatment with Carvykti. ICANS often correlates with CRS but it can occur in the absence of CRS. After treatment with Carvykti, ICANS can occur before, during, or after CRS onset, or after CRS resolution. ICANS may be severe, life-threatening, or fatal.  

Symptoms of neurologic side effects include but are not limited to the following:

• confusion 
• disorientation 
• loss of consciousness 
• seizures 
• tremor 
• slower movements 
• changes in personality 
• depression 
• tingling and numbness of hands and feet 
• leg and arm weakness 
• facial numbness 
• difficulty speaking, reading, or writing.  

It is important to promptly alert the doctor if there is any change in the patient's health or if the patient is not feeling well.  

HLH/MAS  

Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) are aggressive and life-threatening inflammatory conditions of excessive immune system activation. Fatal HLH/MAS reactions have occurred in patients following treatment with Carvykti. HLH/MAS can occur with CRS or with neurologic toxicities. It is important to promptly alert the doctor if there is any change in the patient's health or if the patient is not feeling well.  

Cytopenias  

Cytopenia is a condition in which there is a lower-than-normal number of one or more than one of the patient's blood cell types. Prolonged or recurrent cytopenias have occurred following treatment with Carvykti, with bleeding and infection requiring support with growth factors or blood product transfusion. One or more recurrences of cytopenias are possible after partial or complete recovery of cytopenias. Neutropenia, a reduced level of a type of white blood cells called neutrophils, is associated with increased risk of infection. It is important to promptly alert the doctor if the patient develops fever, chills, or any other signs or symptoms of an infection. 

Hypogammaglobulinemia  

Hypogammaglobulinemia is a laboratory diagnosis made when the immune system is not producing enough immunoglobulin G (IgG) in the blood.  

Hypersensitivity reactions  

Hypersensitivity reactions are any undesirable reactions produced by the immune system. These reactions may be uncomfortable, damaging, or fatal. Patients receiving Carvykti must be monitored for hypersensitivity reactions during the infusion of Carvykti and for at least 2 hours after.  

Secondary malignancies  

A secondary malignancy is a new cancer that is unrelated to a pre-existing cancer diagnosis. Secondary cancers that are a consequence of treatment for the initial cancer may occur months or years after the initial treatment. 

Possible Common Side Effects of Carvykti  

The most common nonlaboratory side effects that occurred in more than 20% of myeloma patients who received Carvykti are the following:

• pyrexia (fever) 
• cytokine release syndrome (CRS) 
• hypogammaglobulinemia 
• hypotension 
• musculoskeletal pain 
• fatigue 
• pathogen-unspecified infections
• cough 
• chills 
• diarrhea 
• nausea 
• encephalopathy 
• decreased appetite 
• upper respiratory tract infection 
• headache 
• tachycardia (fast heartbeat) 
• dizziness 
• dyspnea 
• edema 
• viral infections 
• coagulopathy 
• constipation 
• vomiting 

The most common laboratory side effects that occurred in 50% or more of myeloma patients who received Carvykti include the following:  

• thrombocytopenia 
• neutropenia 
• anemia
• aminotransferase (enzyme) elevation 

Hypoalbuminemia 

It is important to promptly alert the doctor if there is any change in the patient's health or if the patient is not feeling well. Patients should inform the entire healthcare team if they received Carvykti, as it may cause side effects that are severe or life-threatening.  

Immediately contact the doctor or get emergency help if the patient experiences any of the following:  

• fever of 100.4°F/38°C or higher 
• chills or shivering 
• fast or irregular heartbeat 
• difficulty breathing 
• shortness of breath 
• very low blood pressure 
• dizziness or lightheadedness 

Effects on the nervous system, which may be subtle and can occur weeks after infusion of Carvykti: 

• feeling confused 
• disoriented 
• less alert 
• difficulty speaking 
• slurred speech 
• memory loss 
• difficulty reading or writing or understanding words 
• loss of coordination affecting movement and balance 
• slower movements 
• changes in handwriting
• personality changes (including a reduced ability to express emotions)
• being less talkative 
• disinterest in activities 
• reduced facial expression 
• tingling, numbness and pain in hands and/or feet 
• difficulty walking, leg and/or arm weakness 
• difficulty breathing
• facial numbness 
• difficulty moving muscles of face and eyes 

Patients should not be given live vaccines for some time before and after Carvykti treatment. Patients should to talk to their doctor if they need any vaccinations. Patients should not donate blood, organs, tissues, or cells for transplantation. 

Support for Carvykti Patients and Their Care Partners 

The MyCARVYKTI™ Patient Support Program, sponsored by Janssen Biotech Inc. and Legend Biotech, is designed to help eligible patients and their care partners with support during treatment. Patients who meet financial and other eligibility requirements, and their care partners, may receive assistance with transportation, lodging, and out-of-pocket costs related to meals and other travel expenses associated with treatment at a certified treatment center. MyCARVYKTI™ Patient Support Specialists are available to help guide eligible patients through the enrollment process and assist with program benefits. Call 1.800.559.7875. 

Additional Resources: 

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

Highlights of Prescribing Information for CARVYKTI™

From Best of 2021 ASH to 2022 COVID-19 Guidance

Updated Results from CARTITUDE-1: Phase 1b/2Study of Ciltacabtagene Autoleucel in Patients with Relapsed Refractory Multiple Myeloma

New Data from CARTITUDE-1 Study Show Continued Deep and Durable Responses of Ciltacabtagene Autoleucel (cilta-cel) in Treatment of Heavily Pretreated Patients with Multiple Myeloma

A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1)