Ciltacabtagene Autoleucel

Ciltacabtagene Autoleucel is a prescription medication used for the treatment of relapsed or refractory multiple myeloma after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

• Ciltacabtagene Autoleucel is available under the following different brand names: Carvykti

Common side effects of Ciltacabtagene Autoleucel include:

• fever
• cytokine release syndrome
• hypogammaglobulinemia
• low blood pressure (hypotension)
• musculoskeletal pain
• fatigue
• infections
• cough
• chills
• diarrhea
• nausea
• encephalopathy
• decreased appetite
• upper respiratory tract infection
• headache
• fast heart rate
• dizziness
• shortness of breath
• fluid retention (edema)
• coagulopathy
• constipation
• vomiting
• low platelets (thrombocytopenia)
• low white blood cells (neutropenia)
• anemia
• aminotransferase elevation
• low albumin (hypoalbuminemia)

Serious side effects of Ciltacabtagene Autoleucel include:

• rash
• itching
• hives
• swelling of the face, mouth, tongue, or throat 
• chest pain
• fast heartbeat
• difficulty swallowing or breathing

Rare side effects of Ciltacabtagene Autoleucel include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Injection, suspension

• Single-dose units contain specific amounts of T cells depending on the patient’s body weight that are suspended in a patient-specific infusion bag
• Maximum of 1*108 CAR-positive viable T cells per infusion bag of 5% dimethyl sulfoxide

Multiple myeloma

Adult dosage

• One treatment course consists of fludarabine- and cyclophosphamide-lymphodepleting chemotherapy followed by IV infusion of Ciltacabtagene Autoleucel

Lymphodepleting chemotherapy

• Confirm availability of Ciltacabtagene Autoleucel before starting the lymphodepleting chemotherapy regimen
• Fludarabine 30 mg/m2 IV once a day for 3 days
• Cyclophosphamide 300 mg/m2 IV once a day for 3 days starting with the first dose of fludarabine

Ciltacabtagene Autoleucel

• Administer 2–4 days after completing lymphodepleting chemotherapy
• 0.5-1*106 CAR-positive viable T cells/kg IV; not to exceed 1*108 CAR-T cells per single IV infusion
• Administer autologously prepared, weight-based IV infusion for individual patients within 30 minutes by either gravity or peristaltic pump
• Do not use a leukocyte-depleting filter

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Ciltacabtagene Autoleucel has severe interactions with no other drugs
• Ciltacabtagene Autoleucel has serious interactions with at least 202 other drugs
• Ciltacabtagene Autoleucel has moderate interactions with no other drugs
• Ciltacabtagene Autoleucel has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Ciltacabtagene Autoleucel?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Ciltacabtagene Autoleucel?”

Cautions

• Available only through a restricted access program
• Hypogammaglobulinemia can occur; monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic/antiviral prophylaxis, and immunoglobulin replacement standard guidelines
• Secondary malignancies may develop; monitor the patient life-long for secondary malignancies
• Hypersensitivity
  • Allergic reactions may occur during infusion; serious hypersensitivity reactions, including anaphylaxis
  • Monitor for 2 hours after infusion for signs and symptoms of severe reaction; treat promptly and manage patients appropriately according to the severity of the hypersensitivity reaction
• Recurrent cytopenias
  • Prolonged cytopenias may occur and last for several weeks following lymphodepleting chemotherapy and CAR-T cell infusion
  • Monitor blood cell counts before and after infusion
  • Manage cytopenias with growth factors and blood product transfusion support according to local institutional guidelines
  • Hemophagocytic/ macrophage activation syndrome
  • Manifestations of hemophagocytic lymph histiocytosis/macrophage activation syndrome (HLH/MAS) include hypotension, hypoxia with diffuse alveolar damage, coagulopathy, cytopenia, and multiorgan dysfunction, including renal dysfunction; HLH is a life-threatening condition with a high mortality rate if not recognized and treated early
• Patients with HLH/MAS reported having CRS symptoms and neurologic events after infusion
  • Treat HLH/MAS per institutional standards
• Cytokine release syndrome
  • Cytokine release syndrome, including fatal or life-threatening reactions, occurred following treatment in many patients. Closely monitor patients who experience CRS for cardiac and other organ functions until resolution of symptoms
  • Monitor patients who experience Grade 2 or higher CRS (eg, hypotension not responsive to fluids, or hypoxia requiring supplemental oxygenation) with continuous telemetry and pulse oximetry
  • For severe or life-threatening CRS, consider intensive care unit-level monitoring and supportive therapy including tocilizumab, corticosteroids, and antiseizure prophylaxis with levetiracetam
  • Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time
• Infection risk
  • Serious infections, including life-threatening or fatal infections, have been reported; before administering, infection prophylaxis for neutropenia should follow local guidelines; monitor for signs and symptoms of infection after treatment and treat appropriately
  • In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care, as medically indicated
  • Viral reactivation can occur; hepatitis B virus reactivation can result in fulminant hepatitis, hepatic failure, and death; perform screening for cytomegalovirus, HBV, hepatitis C virus, and HIV by clinical guidelines before collection of cells for manufacturing
• Neurologic effects
  • Neurological toxicities, which may be severe or life-threatening, can occur following treatment
  • Neurotoxicity may include immune effector cell-associated neurotoxicity syndrome (ICANS), parkinsonism, Guillain-Barré syndrome, peripheral neuropathy, or cranial nerve palsies
  • Counsel patients on the signs and symptoms of neurologic toxicities, and the delayed nature of onset; instruct patients to seek immediate medical attention for further assessment and management if signs or symptoms of any of these neurologic toxicities occur at any time
  • Monitor patients at least daily for 10 days following infusion at REMS-certified healthcare facility for signs and symptoms of ICANS; rule out other causes of ICANS symptoms; monitor patients for signs or symptoms of ICANS for at least 4 weeks after infusion and treat promptly; neurologic toxicity should be managed with supportive care and/or corticosteroids as needed
  • Monitor patients for signs and symptoms of parkinsonism that may be delayed in onset and managed with supportive care measures; there is limited efficacy information with medications used for the treatment of Parkinson’s disease for improvement or resolution of parkinsonism symptoms following treatment
  • Monitor for GBS; evaluate patients presenting with peripheral neuropathy for GBS; consider treatment of GBS with supportive care measures and in conjunction with immunoglobulins and plasma exchange, depending on the severity of GBS
  • Occurrence of 3rd and 6th cranial nerve palsy, bilateral 7th cranial nerve palsy, worsening of cranial nerve palsy after improvement, and occurrence of peripheral neuropathy in patients with cranial nerve palsy also reported; monitor patients for signs and symptoms of cranial nerve palsies; consider management with systemic corticosteroids, depending on severity and progression of signs and symptoms
  • Owing to the potential for neurological events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following treatment; advise patients to refrain from driving and engaging in hazardous occupations or activities
• Drug interaction overview
  • Immunization with live viral vaccines
    • Safety of immunization with live viral vaccines during or following treatment has not been studied
    • Vaccination with live-virus vaccines is not recommended for at least 6 weeks before lymphodepleting chemotherapy starts, during Ciltacabtagene Autoleucel treatment, and until immune recovery afterward
  • HIV nucleic acid tests
    • HIV and the lentivirus used to make Ciltacabtagene Autoleucel have limited, short spans of identical genetic material (RNA)
    • Therefore, some commercial HIV nucleic acid tests may yield false-positive results

Pregnancy and Lactation

• Data are not available on pregnant women
• No animal reproductive and developmental toxicity studies have been conducted
• Unknown if Ciltacabtagene Autoleucel may potentially transfer to the fetus; based on the mechanism of action, if transduced cells cross the placenta, fetal toxicity, including B-cell lymphocytopenia, may occur; not recommended for women who are pregnant, and consult with treating physician on pregnancy after infusion
• Treated patients may have hypogammaglobulinemia; assess immunoglobulin levels in newborns of treated mothers
• Verify the pregnancy status of women with reproductive potential before initiating treatment
• There is no data on the effects on fertility
• Contraception
  • See prescribing information for fludarabine and cyclophosphamide for information on effective contraception in patients receiving lymphodepleting chemotherapy
  • Insufficient exposure data are available to provide recommendations on the duration of contraception following treatment
• Lactation
  • There is no information regarding the presence of human milk, its effects on breastfed infants, and its effects on milk production