Ciltacabtagene autoleucel (Carvykti)

Brexucabtagene autoleucel: sihl-tuh-KAB-tuh-jeen aw-toh-LOO-sel

Carvykti: car-VIHK-tee

Multiple myeloma

Carvykti is approved for:

• patients with multiple myeloma who were previously treated with at least four different types of therapy (including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody [e.g., daratumumab (Darzalex) or isatuximab-irfc (Sarclisa)]), but their cancer either did not respond to treatment (refractory) or has since returned (relapsed).

Limitations of Use

Carvykti REMS program: Due to the risk of potentially serious side effects, Carvykti is currently only available through a Risk Evaluation and Mitigation Strategy (REMS) program. Hospitals or clinics that dispense Carvykti require certification for the program, ensuring proper monitoring and management of side effects associated with the drug. 
Age: The safety and efficacy of Carvykti have not been established in patients under 18 years of age.
Fertility/Pregnancy/Breastfeeding:The effects of Carvykti on female and male fertility are not known. Carvykti is not recommended for women who are pregnant, and may pose a risk to a developing fetus. Male and female patients are advised to use effective contraception for at least 1 year after receiving Carvykti. The risks associated with Carvykti in a breastfed child are not known. During or after treatment with Carvykti, patients are advised to consult with their doctors to weigh the potential risks and benefits of breastfeeding for their child. 
Effects on the ability to drive and use machines:Patients are advised to refrain from driving, engaging in hazardous occupations or activities, and operating heavy machinery for at least 8 weeks after receiving Carvykti.
Live virus vaccination: Vaccination with live virus vaccines (e.g., chickenpox, measles/mumps/rubella [MMR]) is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during Carvykti treatment, and until immune recovery following treatment with Carvykti.

T cell therapy

• CAR T cell therapy

Target:

• BCMA molecule on plasma cells

Carvykti is made from the patient’s own T cells (a type of white blood cell). In order to make Carvykti, blood is collected from the patient’s vein in a process called leukapheresis. During this process, the white blood cells (including T cells) are separated from the collected blood, and the rest of the blood is returned to the patient. This process usually takes 3 to 6 hours and may need to be repeated. The collected white blood cells are then sent to a specialized manufacturing facility where the patient’s T cells are genetically modified in such a way that they make a protein on their surface called a chimeric antigen receptor (CAR). The modified T cells (“CAR T cells”) are multiplied to create millions of CAR T cells. In addition to T cells, Carvykti may also contain natural killer cells. The multiplied CAR T cell product is then delivered back to the patient through a tube in the vein. The entire process, from leukapheresis to treatment administration, takes about 1-2 months.

Once inside the body, the CAR molecules on the surfaces of the modified CAR T cells can attach to a protein called BCMA on the surface of the cancer cells. When a CAR attaches to BCMA, the T cells recognize the cancer cells and kill them.

Before receiving Carvykti, patients are treated with a 3-day course of chemotherapy (cyclophosphamide and fludarabine) to reduce the number of white blood cells in the patient’s blood. This is done to make room for the CAR T cells and ensure that they have the space and resources to survive in the patient’s blood. Two to 4 days after the completion of this chemotherapy regimen, Carvykti is administered through a tube in the vein (intravenous, i.v.). The administration of Carvykti takes about 30 to 60 minutes. About 30 to 60 minutes before receiving Carvykti, patients receive a fever reducer and an antihistamine to reduce the chance of reactions to the infusion.

Patients are monitored daily for 10 days, and periodically for four weeks following treatment with Carvykti. Patients should plan to stay close to the treatment location for the duration of this monitoring period. Patients should refrain from driving or participating in hazardous activities for at least 8 weeks following treatment with Carvykti.

It is important to keep in mind that each patient’s actual outcome is individual and may be different from the results found in the clinical studies. In addition, with immunotherapy, sometimes it takes several months for responses to be observed.

Multiple myeloma

In a clinical trial, 97 patients with multiple myeloma, who had been previously treated with at least 4 prior lines of treatment (including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody), but their cancer either did not respond to treatment or had since returned, were treated with a single infusion of Carvykti. At a median follow-up of 28 months, 98% of patients had a response to treatment, with 80% of patients seeing their cancer disappear entirely. It has been estimated that 60% of patients who responded to treatment continued to respond for at least 24 months.

Most patients treated with Carvykti experience side effects. The most common side effects associated with Carvykti include fever, cytokine release syndrome (CRS), reduced antibody production, low blood pressure, musculoskeletal pain, fatigue, infections, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia (elevated heart rate), dizziness, difficulty breathing, swelling of the hands and feet, bleeding or clotting issues, constipation, vomiting, and abnormal blood tests.

Some side effects, such as cytokine release syndrome (CRS), neurological toxicities, Parkinsonism, Guillain-Barré syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), hypersensitivity reactions, low blood cell counts (cytopenias), and secondary blood cancers (including myelodysplastic syndrome and acute myeloid leukemia), may be severe or life-threatening. Patients are monitored daily by their health care provider for at least 10 days after the infusion of Carvykti, and periodically for at least four weeks. Patients should remain within a reachable distance of the healthcare facility for the duration of that period. Patients and caregivers receive careful instructions to monitor for signs and symptoms related to these side effects, and the conditions are managed by the healthcare provider.

Cytokine release syndrome (CRS)

CRS is caused by a widespread release of molecules called cytokines, which are involved in inflammation and can affect the function of various organs. Cytokines may be released by the CAR T cells in or by other immune cells in the patient’s body. Symptoms of CRS include high fever, chills, difficulty breathing, severe muscle or joint pain, severe nausea, vomiting, diarrhea, very low blood pressure, and dizziness or lightheadedness. CRS typically occurs between 1 and 10 days after infusion, and the health care provider should be immediately notified if any symptoms occur.

Neurological toxicities

A treatment-related disruption of the blood–brain barrier can lead to the development of neurological toxicities (including Parkinsonism and Guillain-Barre syndrome). Symptoms of neurological toxicities include confusion, altered or decreased consciousness, seizures, loss of balance, and difficulty speaking and understanding. Neurological toxicities typically occur about 7 days after infusion, but could occur up to 8 weeks or later after the infusion.

Hemophagocytic lymphohistiocytosis/Macrophage activation syndrome (HLH/MAS)

Some of the cytokines released during cytokine release syndrome can result in an excessive activation of the immune system, causing HLH/MAS. In HLH/MAS, immune cells such as lymphocytes (in HLH) and macrophages (in MAS) begin attacking and destroying healthy tissues, causing widespread tissue damage and inflammation. Symptoms of HLH/MAS typically occur within 8-9 days of receiving Carvykti, and include low blood pressure, low oxygen levels in the blood, altered organ function, and multiple organ failure.

Interference with lab tests for HIV infection

Some lab tests for HIV infection may yield false-positive results in patients who have received Carvykti.

For a more complete list of possible side effects, see the full prescribing information.

Manufacturer

Janssen Biotech, Inc.

Approval

FDA and EMA

Link to drug website

• US: https://www.carvykti.com/
• Europe: https://www.ema.europa.eu/en/medicines/human/EPAR/carvykti

Last update on March 15, 2024

Brexucabtagene autoleucel: sihl-tuh-KAB-tuh-jeen aw-toh-LOO-sel

Carvykti: car-VIHK-tee

Multiple myeloma

Carvykti is approved for:

• patients with multiple myeloma who were previously treated with at least three different types of therapy (including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody [e.g., daratumumab (Darzalex) or isatuximab-irfc (Sarclisa)]), but their cancer either did not respond to treatment (refractory) or has since returned (relapsed).

Limitations of Use

Limitations: Carvykti should only be administered in a qualified treatment center and by adequately trained healthcare professionals who can ensure proper monitoring and management of side effects associated with the drug.
Age: The safety and efficacy of Carvykti have not been established in patients under 18 years of age.
Fertility/Pregnancy/Breastfeeding: The effects of Carvykti on female and male fertility are not known. Carvykti is not recommended for women who are pregnant, and may pose a risk to a developing fetus. Male and female patients are advised to use effective contraception for at least 1 year after receiving Carvykti. The risks associated with Carvykti in a breastfed child are not known. During or after treatment with Carvykti, patients are advised to consult with their doctors to weigh the potential risks and benefits of breastfeeding for their child. 
Effects on the ability to drive and use machines: Patients are advised to refrain from driving, engaging in hazardous occupations or activities, and operating heavy machinery for at least 8 weeks after receiving Carvykti.
Live virus vaccination: Vaccination with live virus vaccines (e.g., chickenpox, measles/mumps/rubella [MMR]) is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during Carvykti treatment, and until immune recovery following treatment with Carvykti.
Infections: Patients are screened for HIV, hepatitis B and C, and other infectious agents before the collection of cells for manufacturing of Carvykti. Currently there is no experience with manufacturing Carvykti for patients who test positive for HIV or for active hepatitis B or C.

T cell therapy

• CAR T cell therapy

Target:

• BCMA molecule on plasma cells

Carvykti is made from the patient’s own T cells (a type of white blood cell). In order to make Carvykti, blood is collected from the patient’s vein in a process called leukapheresis. During this process, the white blood cells (including T cells) are separated from the collected blood, and the rest of the blood is returned to the patient. This process usually takes 3 to 6 hours and may need to be repeated. The collected white blood cells are then sent to a specialized manufacturing facility where the patient’s T cells are genetically modified in such a way that they make a protein on their surface called a chimeric antigen receptor (CAR). The modified T cells (“CAR T cells”) are multiplied to create millions of CAR T cells. In addition to T cells, Carvykti may also contain natural killer cells. The multiplied CAR T cell product is then delivered back to the patient through a tube in the vein. The entire process, from leukapheresis to treatment administration, takes about 1-2 months.

Once inside the body, the CAR molecules on the surfaces of the modified CAR T cells can attach to a protein called BCMA on the surface of the cancer cells. When a CAR attaches to BCMA, the T cells recognize the cancer cells and kill them.

Before receiving Carvykti, patients are treated with a 3-day course of chemotherapy (cyclophosphamide and fludarabine) to reduce the number of white blood cells in the patient’s blood. This is done to make room for the CAR T cells and ensure that they have the space and resources to survive in the patient’s blood. Two to 4 days after the completion of this chemotherapy regimen, Carvykti is administered through a tube in the vein (intravenous, i.v.). The administration of Carvykti takes about 30 to 60 minutes. About 30 to 60 minutes before receiving Carvykti, patients receive a fever reducer and an antihistamine to reduce the chance of reactions to the infusion.

Patients are monitored for adverse events daily for 14 days, and periodically for an additional two weeks following treatment with Carvykti. Patients should plan to stay close to the treatment location for at least four weeks. Patients should refrain from driving or participating in hazardous activities for at least 8 weeks following treatment with Carvykti.

It is important to keep in mind that each patient’s actual outcome is individual and may be different from the results found in the clinical studies. In addition, with immunotherapy, sometimes it takes several months for responses to be observed.

Multiple myeloma

In a clinical trial, 97 patients with multiple myeloma, who had been previously treated with at least 3 prior lines of treatment (including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody), but their cancer either did not respond to treatment or had since returned, were treated with a single infusion of Carvykti. At a median follow-up of 28 months:

Most patients treated with Carvykti experience side effects. The most common side effects associated with Carvykti include fever, cytokine release syndrome (CRS), reduced antibody production, high or low blood pressure, musculoskeletal pain, problems with movement, stomach pain, fatigue, infections, cough, shortness of breath or difficulty breathing, chills, diarrhea, nausea, encephalopathy, decreased appetite, headache, tachycardia (elevated heart rate), dizziness, swelling of the hands and feet, bleeding or clotting issues, constipation, vomiting, abnormal blood tests, and nerve damage, which may cause tingling, numbness, nerve pain, or loss of sensation.

Some side effects, such as cytokine release syndrome (CRS), neurological toxicities, hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), and low blood cell counts (cytopenias), may be severe or life-threatening. Patients are monitored daily by their health care provider for at least 14 days after the infusion of Carvykti, and periodically for an additional two weeks. Patients should remain within a reachable distance of the healthcare facility for at least 4 weeks following Carvykti infusion. Patients and caregivers receive careful instructions to monitor for signs and symptoms related to these side effects, and the conditions are managed by the healthcare provider.

Cytokine release syndrome (CRS)

CRS is caused by a widespread release of molecules called cytokines, which are involved in inflammation and can affect the function of various organs. Cytokines may be released by the CAR T cells in or by other immune cells in the patient’s body. Symptoms of CRS include high fever, chills, difficulty breathing, severe muscle or joint pain, severe nausea, vomiting, diarrhea, very low blood pressure, and dizziness or lightheadedness. CRS typically occurs between 1 and 10 days after infusion, and the health care provider should be immediately notified if any symptoms occur.

Neurological toxicities

A treatment-related disruption of the blood–brain barrier can lead to the development of neurological toxicities (including Parkinsonism and Guillain-Barre syndrome). Symptoms of neurological toxicities include confusion, altered or decreased consciousness, seizures, loss of balance, and difficulty speaking and understanding. Neurological toxicities typically occur about 7 days after infusion, but could occur up to 8 weeks or later after the infusion.

Hemophagocytic lymphohistiocytosis/Macrophage activation syndrome (HLH/MAS)

Some of the cytokines released during cytokine release syndrome can result in an excessive activation of the immune system, causing HLH/MAS. In HLH/MAS, immune cells such as lymphocytes (in HLH) and macrophages (in MAS) begin attacking and destroying healthy tissues, causing widespread tissue damage and inflammation. Symptoms of HLH/MAS typically occur within 8-9 days of receiving Carvykti, and include low blood pressure, low oxygen levels in the blood, altered organ function, and multiple organ failure.

Interference with lab tests for HIV infection

Some lab tests for HIV infection may yield false-positive results in patients who have received Carvykti.

For a more complete list of possible side effects, see the full prescribing information.

Manufacturer

Janssen Biotech, Inc.

Approval

FDA and EMA

Link to drug website

• US: https://www.carvykti.com/
• Europe: https://www.ema.europa.eu/en/medicines/human/EPAR/carvykti

Last update on March 15, 2024