Ciltacabtagene autoleucel

Ciltacabtagene autoleucel (Carvykti) is a CAR-T therapy used to treat relapsed or refractory multiple myeloma (RRMM). It is an autologous cell therapy, meaning it is made from the patient’s own white blood cells (T cells), which are genetically modified to recognize and destroy multiple myeloma cancer cells. Ciltacabtagene autoleucel is administered as a one-time infusion after a personalized manufacturing process.

Ciltacabtagene autoleucel brand name is Carvykti by Janssen Biotech.

Ciltacabtagene autoleucel FDA-approval is for relapsed or refractory multiple myeloma (RRMM) in adults who have:

• received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent,
• and are refractory to lenalidomide.

Ciltacabtagene autoleucel patients had a 98% overall response rate (ORR) in the Ciltacabtagene autoleucel clinical trial CARTITUDE-1 (NCT03548207).

Ciltacabtagene autoleucel success rate:

• 78% of patients experienced a stringent complete response (sCR), which was the best possible response a participant could have towards treatment.
• 17% of patients experienced a very good partial response (VGPR).
• 3% of patients experienced a partial response (PR).

Carvykti's mechanism of action is a BCMA-directed CAR-T therapy designed to target and eliminate multiple myeloma cells.

Multiple myeloma cancer cells have high levels of a protein called BCMA (B-cell maturation antigen) on their surface. Carvykti therapy works by genetically modifying your collected T cells to recognize and attack these BCMA-expressing myeloma cells. Once modified, the T cells specifically target, attack, and destroy the cancer cells.

The Carvykti treatment process involves:

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

• Avoid ciltacabtagene autoleucel if you have an active infection or inflammatory disorder.
• Do not receive live vaccines before or after treatment.
• Drowsiness & Cognitive Impairment: Refrain from driving or operating heavy machinery for at least 8 weeks after treatment.
• Increased risk of false-positive HIV tests.
• Avoid blood, organ, or tissue donation after receiving ciltacabtagene autoleucel.

Tell your doctor if you have ever had:

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

Pregnancy

Ciltacabtagene autoleucel 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 also will 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.

Common ciltacabtagene autoleucel side effects

Common side effects of ciltacabtagene autoleucel include:

• Fever 79%
• Muscle and joint pain 34%
• Tiredness 28%
• Diarrhea 27%
• Headache 23%
• Low blood pressure 23%
• Nausea 20%
• Constipation 10%
• Upper respiratory tract infection 25%
• Viral infection 23%
• Bacterial infection 15%
• Cough 15%
• Pneumonia 14%
• Hypoxia - low oxygen levels 12%
• Swelling or edema 11%
• Feeling confused, agitated or not like yourself (encephalopathy) 11%
• Pain 10%
• Decreased appetite 10%
• Hypogammaglobulinemia (Immune system disorder) 94%
• Cytokine release syndrome 78%
• Low blood test results including low lymphocytes 99%, neutrophils 95%, white blood cells 94%, platelet 47% and hemoglobin 34%.

These common side effects occurred in at least 10% of ciltacabtagene autoleucel patients in the CARTITUDE-4 clinical trial.

Serious side effects

• Cytokine Release Syndrome (CRS) – Tell your caregivers right away if you have signs or symptoms of 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 (tocilizumab and corticosteroids) available to quickly treat CRS if it occurs.
• Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) – May cause confusion, memory loss, and seizures.
• Prolonged Cytopenias – Risk of anemia, thrombocytopenia, and the need for stem cell transplantation.
• Secondary Malignancies – Increased risk of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and T-cell malignancies.
• Neurological Disorders – Reports of Parkinsonism and Guillain-Barré syndrome.
• Immune-effector cell-associated enterocolitis (IEC-EC): – Severe or persistent diarrhea or ruptured bowel have been reported, 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 ciltacabtagene autoleucel to standard therapy.

• 14% in the ciltacabtagene autoleucel arm died compared to 12% in the standard therapy arm.
• The increased death rate occurred before and after receiving ciltacabtagene autoleucel 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 ciltacabtagene autoleucel continues to outweigh the potential risks.

Patients should be closely monitored for any adverse reactions. Contact a healthcare provider immediately if experiencing severe side effects.

These are not all of the possible side effects of Carvykti. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088

• Recommended dose: 0.5-1.0×10^6 CAR-positive viable T cells per kg, with a maximum dose of 1×10^8 CAR-positive viable T cells per infusion.
• Pre-medication required: Acetaminophen and an H1-antihistamine before infusion.
• 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.

HCPs and patients often use the Ciltacabtagene Autoleucel Package Insert (Carvykti) for more detailed information about this medicine. The Ciltacabtagene Autoleucel 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 Ciltacabtagene Autoleucel Prescribing Information (PI).

• Do not drive, or operate heavy machinery, or do other activities that could be dangerous if you are not mentally alert, for at least 2 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.

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.

Active ingredient: ciltacabtagene autoleucel

Carvykti Inactive ingredients: DMSO

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

Marketing Partner: Legend Biotech, Somerset, NJ, USA.