Version July 2025
Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with ciltacabtagene autoleucel. Do not administer ciltacabtagene autoleucel 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), which may be fatal or life-threatening, occurred following treatment with ciltacabtagene autoleucel, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with ciltacabtagene autoleucel. Provide supportive care and/or corticosteroids as needed.
Parkinsonism and Guillain-Barré syndrome (GBS) and their associated complications resulting in fatal or life-threatening reactions have occurred following treatment with ciltacabtagene autoleucel.
Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), including fatal and life-threatening reactions, occurred in patients following treatment with ciltacabtagene autoleucel. HLH/MAS can occur with CRS or neurologic toxicities.
Prolonged and/or recurrent cytopenias with bleeding and infection and requirement for stem cell transplantation for hematopoietic recovery occurred following treatment with ciltacabtagene autoleucel.
Secondary hematological malignancies, including myelodysplastic syndrome and acute myeloid leukemia, have occurred in patients following treatment with ciltacabtagene autoleucel. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including ciltacabtagene autoleucel.
Ciltacabtagene autoleucel is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI REMS Program.
Dosage guidance:
Safety: For autologous use only. Confirm patient identity matches cassette and infusion bag prior to infusion. Confirm availability of autologous ciltacabtagene autoleucel prior to initiating lymphodepleting chemotherapy. Confirm that tocilizumab and emergency equipment are available prior to ciltacabtagene autoleucel infusion and during recovery period. Premedicate with acetaminophen 650 to 1,000 mg orally or IV and diphenhydramine 25 to 50 mg IV or orally (or other H1 antihistamine) 30 to 60 minutes prior to ciltacabtagene autoleucel infusion. Avoid prophylactic dexamethasone or other systemic corticosteroids, as corticosteroids may interfere with ciltacabtagene autoleucel activity.
Clinical considerations: A treatment course consists of 1) lymphodepleting chemotherapy (with fludarabine and cyclophosphamide) for 3 days, and 2) ciltacabtagene autoleucel infusion 2 to 4 days after completion of lymphodepleting chemotherapy. Administer prophylactic antimicrobials as clinically indicated for up to 6 months (or longer) according to standard institutional guidelines or consistent with post American Society for Transplantation and Cellular Therapy consensus (Ref). Consider antiviral therapy to prevent viral reactivation as appropriate. Counsel patients on infection prevention measures and follow institution protocols for vaccination and management of immunocompromised patients with COVID-19.
Lymphodepleting chemotherapy: Delay lymphodepleting regimen for unresolved serious adverse events (eg, clinically significant active infection, cardiac toxicity, pulmonary toxicity) from preceding bridging therapies or active graft-versus-host disease from prior allogeneic hematopoietic cell transplant. Consider repeating lymphodepleting regimen if ciltacabtagene autoleucel infusion is delayed by >14 days and patient has recovered from toxicity of the initial lymphodepleting regimen.
Multiple myeloma, relapsed or refractory: Note: Delay ciltacabtagene autoleucel for clinically significant active infection or inflammatory disorders or for ≥ grade 3 nonhematologic toxicity due to lymphodepleting chemotherapy (excluding grade 3 nausea, vomiting, diarrhea, or constipation) until recovered to ≤ grade 1.
Target dose range: IV: 0.5 to 1 × 106 chimeric antigen receptor (CAR)-positive viable T cells per kg of body weight (Ref); maximum dose: 1 × 108 CAR-positive viable T cells per single infusion.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, mild or moderate kidney impairment did not impact ciltacabtagene autoleucel pharmacokinetics.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatic impairment prior to treatment initiation:
Mild impairment (total bilirubin ≤ ULN and AST > ULN or total bilirubin >1 to ≤1.5 × ULN): There are no dosage adjustments provided in the manufacturer's labeling; however, mild impairment did not impact ciltacabtagene autoleucel pharmacokinetics.
Moderate or severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Cytokine release syndrome: Monitor for cytokine release syndrome (CRS); if fever, hypoxia, and hypotension occur, evaluate for other causes, and manage as appropriate. If CRS is suspected, manage according to the CRS table at the first sign of CRS. If CRS occurs, monitor closely for cardiac and other organ function abnormalities until resolution of symptoms; consider antiseizure prophylaxis with levetiracetam. Monitor patients with ≥ grade 2 CRS (eg, hypotension unresponsive to fluids or hypoxia requiring supplemental oxygen) with continuous cardiac telemetry and pulse oximetry. Consider intensive care monitoring and supportive therapy for severe or life-threatening CRS.
Consider alternate treatment options (eg, higher corticosteroid dose, alternative anticytokine agents, anti–T-cell therapies) for CRS refractory to first-line interventions (tocilizumab or tocilizumab and corticosteroids). Refractory CRS is characterized by fevers, end-organ toxicity (eg, hypoxia, hypotension) not improving within 12 hours of first-line interventions, or development of hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).
If concurrent neurologic toxicity is suspected during CRS, administer more aggressive corticosteroid intervention (based on the CRS and neurotoxicity tables), tocilizumab (according to the CRS table), and antiseizure mediations (according to the neurotoxicity table).
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CRS grade |
Tocilizumaba |
Corticosteroidsb |
|---|---|---|
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a Also see tocilizumab monograph. | ||
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b If corticosteroids are initiated, continue corticosteroids until ≤ grade 1; taper corticosteroids if total corticosteroid exposure is >3 days. | ||
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c Attributed to CRS. Fever may not always be present concurrently with hypotension or hypoxia (may be masked by antipyretics and/or anticytokine therapy, such as tocilizumab or steroids). The absence of fever does not impact CRS management; CRS management is driven by hypotension and/or hypoxia and by the more severe symptom not attributable to any other cause. | ||
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dLow-flow nasal cannula is ≤6 L/min; high-flow nasal cannula is >6 L/min. | ||
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eFor unresponsive CRS, monoclonal antibodies that target cytokines may be considered (based on institutional practice). | ||
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Grade 1: Temperature ≥38°C (100.4°F)c |
If onset is <72 hours after cell infusion, consider tocilizumab 8 mg/kg (maximum dose: 800 mg) IV over 1 hour. |
– |
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Grade 2: Symptoms require and respond to moderate intervention. Temperature ≥38°C (100.4°F)c with: Hypotension not requiring vasopressors, and/or Hypoxia requiring oxygen via cannulad or blow by, or Grade 2 organ toxicity |
Administer tocilizumab 8 mg/kg (maximum dose: 800 mg) IV over 1 hour. Repeat tocilizumab every 8 hours, as needed, if not responsive to IV fluids up to 1 L or increasing supplemental oxygen. |
Consider dexamethasone 10 mg IV every 12 to 24 hours. |
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If no improvement within 24 hours or rapid progression, repeat tocilizumab and escalate dexamethasone to 20 mg IV every 6 to 12 hours. If no improvement within 24 hours or continued rapid progression, switch to methylprednisolone 2 mg/kg IV every 12 hours. After 2 tocilizumab doses, consider alternative anticytokine agentse. Do not exceed 3 tocilizumab doses per 24 hours, and maximum total of 4 tocilizumab doses. | ||
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Grade 3: Symptoms require and respond to aggressive intervention. Temperature ≥38°C (100.4°F)c with: Hypotension requiring one vasopressor ± vasopressin, and/or Hypoxia requiring oxygen via high-flow nasal cannulad, face mask, non-rebreather mask, or Venturi mask, or Grade 3 organ toxicity or grade 4 transaminitis. |
Administer tocilizumab 8 mg/kg (maximum dose: 800 mg) IV over 1 hour. Repeat tocilizumab every 8 hours, as needed, if not responsive to IV fluids up to 1 L or increasing supplemental oxygen. |
Consider dexamethasone 10 mg IV every 12 hours. |
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If no improvement within 24 hours or rapid progression, repeat tocilizumab and escalate dexamethasone to 20 mg IV every 6 to 12 hours. If no improvement within 24 hours or continued rapid progression, switch to methylprednisolone 2 mg/kg IV every 12 hours. After 2 tocilizumab doses, consider alternative anticytokine agentse. Do not exceed 3 tocilizumab doses per 24 hours, and maximum total of 4 tocilizumab doses. | ||
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Grade 4: Life-threatening symptoms. Requires ventilator support, CVVHD. Temperature ≥38°C (100.4°F)c with: Hypotension requiring multiple vasopressor (excluding vasopressin), and/or Hypoxia requiring oxygen positive pressure (eg, CPAP, BiPAP, intubation, and mechanical ventilation), or Grade 4 organ toxicity (excluding transaminitis) |
Administer tocilizumab 8 mg/kg (maximum dose: 800 mg) IV over 1 hour. Repeat tocilizumab every 8 hours, as needed, if not responsive to IV fluids up to 1 L or increasing supplemental oxygen. |
Administer dexamethasone 20 mg IV every 6 hours. |
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After 2 tocilizumab doses, consider alternative anticytokine agentse. Do not exceed 3 tocilizumab doses per 24 hours, and maximum total of 4 tocilizumab doses. If no improvement within 24 hours, consider methylprednisolone (1 to 2 g IV, repeat every 24 hours, if needed; taper as clinically indicated) or other immunosuppressants (eg, other anti–T-cell therapies). | ||
Neurotoxicity: Monitor for signs/symptoms of neurologic toxicities, including immune effector cell-associated neurotoxicity syndrome (ICANS) and other neurotoxicities. Rule out other causes of neurologic signs/symptoms. Provide intensive care and supportive therapy for severe or life-threatening neurologic toxicities. If ICANS is suspected, manage according to the neurotoxicity table. If concurrent CRS is suspected during neurotoxicity, administer more aggressive corticosteroid intervention (based on the CRS and neurotoxicity tables), tocilizumab (according to the CRS table), and antiseizure mediations (according to the neurotoxicity table). ICANS grading/management is determined by the most severe event (ICE [immune effector cell-associated encephalopathy] score, level of consciousness, seizure, motor findings, raised intracranial pressure ([ICP]/cerebral edema) that is not attributable to any other cause.
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Neurotoxicity (ICANS) grade |
Corticosteroids and antiseizure medication |
|---|---|
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a Dexamethasone or dexamethasone equivalent. | |
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b If patient is arousable and able to perform ICE assessment, assess:
If patient is unarousable and unable to perform ICE assessment (Grade 4 ICANS) = 0 points. | |
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c Intracranial hemorrhage ± associated edema is not considered a neurotoxicity feature and is excluded from ICANS grading. | |
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d Tremors and myoclonus associated with immune effector cell therapies may be graded; however, they do not influence ICANS grading. | |
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Grade 1 ICE score 7 to 9b or Depressed level of consciousness; awakens spontaneously |
Consider dexamethasonea 10 mg IV every 12 to 24 hours for 2 to 3 days. Consider nonsedating antiseizure medications (eg, levetiracetam) for seizure prophylaxis. |
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Grade 2 ICE score 3 to 6b or Depressed level of consciousness; awakens to voice |
Initiate dexamethasonea 10 mg IV every 12 hours for 2 to 3 days (or longer for persistent symptoms). Consider corticosteroid taper if total corticosteroid exposure is >3 days. If no improvement after 24 hours or worsening of neurologic toxicity, increase dexamethasonea dose and/or frequency up to a maximum of 20 mg IV every 6 hours. Consider nonsedating antiseizure medications (eg, levetiracetam) for seizure prophylaxis. |
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Grade 3 ICE score 0 to 2b (if ICE score is 0, but the patient is arousable [eg, awake with global aphasia] and able to perform assessment) or Depressed level of consciousness; awakens only to tactile stimulus or Seizures (any clinical seizure, focal or generalized, that resolves rapidly, or nonconvulsive seizures on EEG that resolve with intervention) or Raised ICP: Focal/local edema on neuroimagingc |
Initiate dexamethasonea 10 to 20 mg IV every 6 hours. If no improvement after 24 hours, or worsening neurologic toxicity, escalate dexamethasonea dose to at least 20 mg IV every 6 hours or escalate to high-dose methylprednisolone (1 to 2 g/day, repeat every 24 hours if needed; taper as clinically indicated). Consider non-sedating antiseizure medications (eg, levetiracetam) for seizure prophylaxis. If cerebral edema is suspected, consider hyperventilation and hyperosmolar therapy. Administer methylprednisolone 1 to 2 g IV, repeat every 24 hours, if needed; taper as clinically indicated. |
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Grade 4 ICE score 0b or Depressed level of consciousness; either patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse, or stupor or coma or Seizures (life-threatening prolonged seizure [>5 minutes], or repetitive clinical or electrical seizures without return to baseline in between) or Motor findingsd (deep focal motor weakness, such as hemiparesis or paraparesis) or Raised ICP/cerebral edema, with signs/symptoms, such as: diffuse cerebral edema on neuroimaging, decerebrate or decorticate posturing, cranial nerve VI palsy, papilledema, or Cushing’s triad |
Initiate dexamethasonea 20 mg IV every 6 hours. If no improvement after 24 hours, or worsening neurologic toxicity, escalate to high-dose methylprednisolone (1 to 2 g IV per day, repeat every 24 hours, if needed; taper as clinically indicated). Consider nonsedating antiseizure medications (eg, levetiracetam) for seizure prophylaxis. If raised ICP/cerebral edema is suspected, consider hyperventilation and hyperosmolar therapy. Administer high-dose methylprednisolone (1 to 2 g IV per day, repeat every 24 hours, if needed; taper as clinically indicated). Consider neurology and/or neurosurgery consultation. |
Other toxicities:
Cranial nerve palsies: Consider management with systemic corticosteroids (depending on the severity and progression of signs/symptoms).
Cytopenias: Manage cytopenia with growth factor and blood product transfusion support (according to local institutional guidelines).
Guillain-Barré syndrome: Consider treatment with supportive care measures and in conjunction with IV immunoglobulin and plasma exchange (depending on the severity).
Hemophagocytic lymphohistiocytosis/macrophage activation syndrome: Manage per institutional standards (which may include transfusion).
Hypersensitivity: Manage promptly and appropriately based on the severity of the hypersensitivity reaction.
Hypogammaglobulinemia (IgG <400 mg/dL): Administer IV immune globulin and manage as indicated per local institutional guidelines, including infection precautions and antibiotic and/or antiviral prophylaxis.
Infection: Administer prophylactic, preemptive, and/or therapeutic antimicrobials according to standard institutional guidelines. If infection occurs, manage appropriately.
Neutropenic fever: Evaluate for infection, and manage with broad-spectrum antibiotics, fluids, and other supportive care, as clinically indicated.
Parkinsonism: Manage with supportive care measures.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Cardiovascular: Edema (11% to 23%), hypertension (7% to 19%), hypotension (23% to 51%), tachycardia (5% to 27%)
Gastrointestinal: Constipation (10% to 22%), decreased appetite (10% to 29%), diarrhea (27% to 33%; grades ≥3: 1% to 3%), nausea (20% to 31%; grades ≥3: 1%), vomiting (5% to 20%)
Hematologic & oncologic: Anemia (grades 3/4: 72%), disorder of hemostatic components of blood (5% to 22%; grades ≥3: 2%; including disseminated intravascular coagulation, hypofibrinogenemia, increased INR, prolonged partial thromboplastin time, prolonged prothrombin time), hemorrhage (9% to 16%; grades ≥3: 4%), hypogammaglobulinemia (93% to 94%; grades ≥3: 2% to 9%), lymphocytopenia (grades 3/4: 99%), neutropenia (grades 3/4: 98%), thrombocytopenia (grades 3/4: 63%)
Hepatic: Increased serum aspartate aminotransferase (grades 3/4: 21%)
Hypersensitivity: Cytokine release syndrome (78% to 95%; serious: 6% to 21%)
Immunologic: Antibody development (20% to 21%)
Infection: Infection (41%; including bacterial infection [9% to 15%], fungal infection [3%], viral infection [23%])
Nervous system: Chills (6% to 33%), dizziness (9% to 23%), encephalopathy (11% to 30%), fatigue (28% to 47%), headache (23% to 27%), insomnia (13%), motor dysfunction (9% to 16%), neurotoxicity (including cranial nerve palsy [3% to 9%], Guillain-Barre syndrome, immune effector cell-associated neurotoxicity syndrome [ICANS: 7% to 23%], myelitis [immune mediated], parkinsonism [1% to 6%], peripheral neuropathy [7%; grade 3: ≤2%])
Neuromuscular & skeletal: Musculoskeletal pain (34% to 48%)
Respiratory: Cough (15% to 39%), dyspnea (10% to 23%), hypoxia (12%), nasal congestion (15%), pneumonia (14%), upper respiratory tract infection (25% to 28%)
Miscellaneous: Fever (79% to 96%)
1% to 10%:
Cardiovascular: Capillary leak syndrome (1%), cardiac arrhythmia (3% to 8%), chest pain (7%), thrombosis (3% to 5%)
Dermatologic: Skin rash (7% to 8%)
Endocrine & metabolic: Hypertriglyceridemia (grades 3/4: <10%), hypoalbuminemia (grades 3/4: <10%), hypocalcemia (grades 3/4: <10%), hypokalemia (grades 3/4: <10%), hypomagnesemia (grades 3/4: <10%), hyponatremia (grades 3/4: <10%), hypophosphatemia (10%), increased serum iron (hyperferritinemia: 7%)
Gastrointestinal: Abdominal pain (6%), dysphagia (1%), gastroenteritis (7%)
Genitourinary: Urinary tract infection (4% to 5%)
Hematologic & oncologic: C-reactive protein increased (6%), febrile neutropenia (2% to 10%; grades ≥3: 9%), hematologic malignancy (3% to 10%; including myelodysplastic syndrome, myeloid leukemia [acute], T-cell lymphoma), hemophagocytic lymphohistiocytosis (including macrophage activation syndrome: 1%), lymphocytosis (2%), tumor lysis syndrome (1%)
Hepatic: Increased gamma-glutamyl transferase (grades 3/4: <10%), increased serum alanine aminotransferase (grades 3/4: <10%), increased serum alkaline phosphatase (grades 3/4: <10%), increased serum bilirubin (grades 3/4: <10%)
Hypersensitivity: Hypersensitivity reaction (5%)
Infection: Sepsis (9% to 10%)
Nervous system: Aphasia (3% to 8%), ataxia (3% to 8%), cerebrovascular accident (1%), cogwheel rigidity (1%), delirium (2% to 5%), depression (4%), falling (3%), mask-like face (3%), pain (10%), paresis (1%), personality changes (2%), psychomotor impairment (1%), seizure (1%), sleep disturbance (6%), speech disturbance (slow speech: 1%), tremor (4% to 6%), writing difficulty (3%; micrographia: 4%)
Neuromuscular & skeletal: Abnormal posture (1%), bradykinesia (2%)
Ophthalmic: Diplopia (1%), nystagmus disorder (1%)
Renal: Kidney failure (5% to 7%)
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Cytokine release syndrome: Cytokine release syndrome (CRS), including fatal or life-threatening reactions, commonly occurred with ciltacabtagene autoleucel; grade 3 or higher CRS has occurred. The median time to onset of CRS was 7 days (range: 1 to 23 days). CRS resolved in a majority of patients with a median duration of 4 days (range: 1 to 97 days). In patients who experienced CRS, the most common manifestations included fever, hypotension, and/or increased AST. Serious events that may be associated with CRS included fever, respiratory failure, disseminated intravascular coagulation, capillary leak syndrome, hemophagocytic lymphohistiocytosis, and supraventricular and ventricular tachycardia. CRS has been reported to be associated with findings of hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS); the physiology of the syndromes may overlap. HLH/MAS may be life-threatening. Patients should seek immediate medical attention if signs/symptoms of CRS occur at any time.
• Cytopenias: Prolonged and/or recurrent cytopenias have occurred following lymphodepleting chemotherapy and ciltacabtagene autoleucel. Prolonged (unresolved by day 30 after ciltacabtagene autoleucel infusion) ≥ grade 3 anemia, lymphopenia, neutropenia, and thrombocytopenia have been reported. Recurrent grade 3 or 4 neutropenia, thrombocytopenia, lymphopenia, and anemia were observed after recovery from initial grade 3 or 4 cytopenias.
• Early death: A higher proportion of patients treated with ciltacabtagene autoleucel experienced death within 10 months of randomization when compared to standard regimens in the CARTITUDE-4 clinical trial. Early death either prior to or following ciltacabtagene autoleucel infusion occurred secondary to disease progression or adverse events (most commonly infection).
• Hemophagocytic lymphohistiocytosis/macrophage activation syndrome: HLH/MAS has been observed with ciltacabtagene autoleucel. HLH is a life-threatening condition with a high mortality rate if not recognized and managed early. All cases developed within 99 days of ciltacabtagene infusion (in the setting of ongoing or worsening CRS); the median time to onset was 10 days (range: 8 to 99 days). Manifestations of HLH/MAS include hyperferritinemia, hypotension, hypoxia with diffuse alveolar damage, coagulopathy and hemorrhage, cytopenia, and multiorgan dysfunction, including kidney dysfunction and respiratory failure. HLH/MAS is associated with an increased risk of severe bleeding.
• Hypersensitivity: Hypersensitivity reactions have occurred following ciltacabtagene autoleucel infusion; all reactions were ≤ grade 2. Symptoms included flushing, chest discomfort, tachycardia, wheezing, tremor, burning sensation, noncardiac chest pain, and fever. Serious hypersensitivity reactions, including anaphylaxis, may be due to the dimethyl sulfoxide (DMSO) in ciltacabtagene autoleucel.
• Hypogammaglobulinemia: Hypogammaglobulinemia can occur with ciltacabtagene autoleucel. IgG levels fell below 500 mg/dL in a majority of patients. Some patients required IV immunoglobulin following ciltacabtagene autoleucel, for either management of an adverse reaction or for prophylaxis.
• Infections: Severe, life-threatening, or fatal infections have occurred with ciltacabtagene autoleucel, including viral, bacterial, and fungal infections, as well as unspecified pathogens. Neutropenic fever has been reported; may be concurrent with CRS. Hepatitis B virus reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients with hypogammaglobulinemia. Increased rates of fatal COVID-19 infections have been reported in patients who received ciltacabtagene autoleucel; follow guidelines for immunization and management of immunocompromised patients with COVID-19 and counsel patients in the importance of infection prevention.
• Neurologic toxicities: Neurologic toxicities, which may be severe, life-threatening, or fatal, have occurred with ciltacabtagene autoleucel. Neurologic toxicities included immune effector cell-associated neurotoxicity syndrome (ICANS), neurotoxicity with signs/symptoms of parkinsonism, Guillain-Barré syndrome (GBS), immune-mediated myelitis, peripheral neuropathies, and cranial nerve palsies. Patients should seek immediate medical attention for further assessment and management if signs or symptoms of any of these neurologic toxicities occur at any time (including delayed-onset neurotoxicity). In patients treated with ciltacabtagene autoleucel, approximately one-fourth developed ≥1 neurologic toxicity; a majority of patients developing neurologic toxicity also developed CRS. The median time to onset of neurologic toxicity was 10 days (range: 1 to 101 days), with most cases developing by day 30. Neurologic toxicity resolved in approximately three-fourths of patients; the median time to resolution was 23 days (range: 1 to 544 days). Due to the potential for neurologic events, including altered mental status, seizures, neurocognitive decline, or neuropathy, patients receiving ciltacabtagene autoleucel are at risk for altered/decreased consciousness or coordination in the 8 weeks following ciltacabtagene autoleucel infusion and should refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery during this initial period, and in the event of new onset of any neurologic toxicities.
ICANS: ICANS, which may be fatal or life-threatening, occurred with ciltacabtagene autoleucel, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS; grade 3 or higher ICANS occurred. Common manifestations of ICANS included encephalopathy, aphasia, headache, motor dysfunction, ataxia, and sleep disorder. The median time to onset of ICANS was 8 days (range: 1 to 28 days) and the median duration of ICANS was 6 days (range: 1 to 1,229 days). ICANS resolved in over three-fourths of patients; the median time to resolution was 3 days (range: 1 to 143 days). A majority of patients who developed ICANS also developed CRS.
Parkinsonism: Parkinsonism and associated complications have occurred following treatment with ciltacabtagene autoleucel; onset of symptoms occurred after CRS in all cases and after ICANS in most cases. Manifestations of parkinsonism included movement disorders, cognitive impairment, and personality changes. The median time to onset of parkinsonism was 56 days (range: 14 to 914 days) and the median duration of parkinsonism was ~244 days (range: 62 to 720 days). Parkinsonism resolved in a small number of patients with a median time to resolution of 523 days. There is limited efficacy data with medications used for the treatment of Parkinson disease for the improvement of resolution of parkinsonism associated with ciltacabtagene autoleucel.
GBS: GBS and associated complications have occurred, including a case report with a fatal outcome despite treatment with IV immunoglobulin; symptoms included those consistent with Miller-Fisher variant of GBS, encephalopathy, motor weakness, speech disturbances, and polyradiculoneuritis.
Myelitis: Grade 3 immune-mediated myelitis has occurred 25 days following ciltacabtagene autoleucel treatment. Symptoms included hypoesthesia of the lower extremity and lower abdomen with impaired sphincter control. Although myelitis was ongoing at the time of death (from other cause), symptoms improved with corticosteroids and IV immune globulin.
Peripheral neuropathy: Some patients developed peripheral neuropathy, including grade 3 events, following treatment with ciltacabtagene autoleucel. The median time of symptom onset was 57 days (range: 1 to 914 days) and the median duration was ~150 days (range: 1 to 692 days), including those with ongoing neuropathy. Peripheral neuropathy resolved in approximately half of patients; the median time to resolution was 58 days (range: 1 to 215 days). Patients who experience peripheral neuropathy may also experience cranial nerve palsies or GBS.
Cranial nerve palsies: Some patients experienced cranial nerve palsies; the median time to onset was 21 days (range: 17 to 101 days) and median duration of 70 days (range: 1 to 262 days). A majority of cases resolved with a median time to resolution of 66 days (range: 1 to 209 days). The most frequently affected cranial nerve was the seventh cranial nerve; cranial nerves III, V, and VI have also been affected.
• Secondary malignancies: Patients treated with ciltacabtagene autoleucel may develop secondary malignancies. Myeloid neoplasms (including myelodysplastic syndrome [MDS], acute myeloid leukemia [AML], and MDS followed by AML) have occurred. The median time to the development of myeloid neoplasms was 447 days (range: 56 to 870 days) following treatment with ciltacabtagene autoleucel. Some cases of myeloid neoplasm occurred following initiation of subsequent antimyeloma treatment. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including ciltacabtagene autoleucel. Mature T-cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion and may include fatal outcomes. If a secondary malignancy develops, contact the manufacturer (1-800-526-7736) for reporting and to obtain instructions on collection of patient samples for testing.
Concurrent drug therapy issues:
• Immunizations: Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during ciltacabtagene autoleucel treatment, and until immune recovery following ciltacabtagene autoleucel treatment. Immunization with live viral vaccines during or following ciltacabtagene autoleucel has not been studied.
Special populations:
• Older age: The incidence of neurologic toxicities (all grade and ≥ grade 3) was higher in patients ≥65 years of age, compared to patients <65 years of age.
Dosage form specific issues:
• Dimethyl sulfoxide: Ciltacabtagene autoleucel contains DMSO, which is associated with serious hypersensitivity reactions, including anaphylaxis.
• Universal precautions: Ciltacabtagene autoleucel contains human blood cells that are genetically modified with replication-incompetent, self-inactivating, lentiviral vector; follow universal precautions and facility biosafety guidelines for handling and disposal to avoid potential transmission of infectious diseases.
Other warnings/precautions:
• REMS program: Ciltacabtagene autoleucel is available only through a restricted program under a risk evaluation and mitigation strategy (REMS) called the CARVYKTI REMS Program. Further information is available at www.carvyktirems.com or 1-844-672-0067.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Intravenous [preservative free]:
Carvykti: 100000000 CELLS (1 ea)
No
Suspension (Carvykti Intravenous)
100000000CELLS (per each): $0.00
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IV: For IV use only. Administer in a health care facility. Coordinate the timing of administration with thawing. Prime tubing set with NS prior to infusion. Once thawed, administer the entire contents of the bag by IV infusion within 2.5 hours using infusion sets fitted with an in-line filter (do not use a leukodepleting filter). Gently mix the contents of the bag during ciltacabtagene autoleucel infusion to disperse cell clumps. After the entire contents of infusion bag has infused, flush the administration line (including the in-line filter) with a volume of NS ≥ the total volume capacity of the administration set (including drip tube) to ensure all product is delivered. A central line may be used for administration (and is encouraged in patients with poor peripheral access). Monitor closely for 2 hours after infusion for signs and symptoms of severe hypersensitivity reaction. Apply universal precautions for product handling.
Prior to administration: Ensure tocilizumab (at least 2 doses) and emergency equipment are available prior to infusion and during recovery period. Confirm patient identity and match to patient identifiers on the infusion bag (do not infuse if identifiers do not match). Premedicate with acetaminophen 650 to 1,000 mg orally and diphenhydramine 25 to 50 mg IV or orally (or other H1 antihistamine) ~30 to 60 minutes prior to ciltacabtagene autoleucel infusion. Avoid prophylactic dexamethasone or other systemic corticosteroids, as they may interfere with the ciltacabtagene autoleucel activity.
Monitor patient daily (for signs/symptoms of cytokine release syndrome and neurotoxicity) at the health care facility for at least 10 days after cell infusion; monitor periodically for 4 weeks for signs/symptoms of delayed neurotoxicity. Patient should remain within proximity of the facility for at least 4 weeks after infusion.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Carvykti: https://www.janssenlabels.com/package-insert/product-patient-information/CARVYKTI-medication-guide.pdf
Multiple myeloma, relapsed or refractory: Treatment of relapsed or refractory multiple myeloma in adults who have received ≥1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide.
Ciltacabtagene autoleucel may be confused with axicabtagene ciloleucel, betibeglogene autotemcel, brexucabtagene autoleucel, elivaldogene autotemcel, exagamglogene autotemcel, idecabtagene vicleucel, lifileucel, lisocabtagene maraleucel, lovotibeglogene autotemcel, sipuleucel-T, tisagenlecleucel.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Miscellaneous Oncologic Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
Corticosteroids (Systemic): May decrease therapeutic effects of CAR-T Cell Immunotherapy. Corticosteroids (Systemic) may increase adverse/toxic effects of CAR-T Cell Immunotherapy. Specifically, the severity and duration of neurologic toxicities may be increased. Management: Avoid use of corticosteroids as premedication before treatment with CAR-T cell immunotherapy agents. Corticosteroids are indicated and may be required for treatment of toxicities such as cytokine release syndrome or neurologic toxicity. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): CAR-T Cell Immunotherapy may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: The CDC recommends that CAR-T-cell recipients who received COVID-19 vaccine prior to or during treatment with CAR-T-cell therapy should be revaccinated with a primary vaccine series at least 3 months (12 weeks) after CAR-T-cell therapy. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Mumps- Rubella- or Varicella-Containing Live Vaccines may increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Verify pregnancy status prior to treatment initiation in patients who could become pregnant.
Patients were required to use contraception during therapy and for 1 year after the ciltacabtagene autoleucel infusion in clinical studies. Patients who could become pregnant were required to use a highly effective method of contraception. Patients with partners who could become pregnant were required to use a barrier method of contraception.
Animal reproduction and toxicity studies have not been conducted. Based on the mechanism of action, in utero exposure to ciltacabtagene autoleucel may cause fetal toxicity, including B-cell lymphocytopenia and hypogammaglobulinemia.
It is not known if ciltacabtagene autoleucelis present in breast milk.
According to the manufacturer, the decision to breastfeed should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Screen for cytomegalovirus, hepatitis B virus (HBV), hepatitis C virus, and HIV or any other infectious agents if clinically indicated in prior to collection of cells (for manufacturing) in accordance with clinical guidelines. Monitor blood counts prior to and after ciltacabtagene autoleucel infusion; monitor hematologic parameters in patients who develop hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Monitor immunoglobulin levels (IgG) after treatment. Consider laboratory testing to monitor for disseminated intravascular coagulation, as well as pulmonary, cardiac, renal, and hepatic function. Verify pregnancy status prior to treatment initiation (in patients who could become pregnant).
Monitor for cytokine release syndrome (CRS) and signs/symptoms of neurotoxicity during therapy and for at least 4 weeks after infusion. For ≥ grade 2 CRS, perform continuous cardiac telemetry and pulse oximetry. Monitor patient daily (for signs/symptoms of cytokine release syndrome and neurotoxicity [including immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms]) at the health care facility for at least 10 days after cell infusion; monitor periodically for 4 weeks for signs/symptoms of delayed neurotoxicity. Monitor for neurotoxicity after ciltacabtagene autoleucel treatment; monitor for signs/symptoms of immune-mediated myelitis, parkinsonism (onset may be delayed), peripheral neuropathy, Guillain-Barré syndrome (GBS; patients presenting with peripheral neuropathy should be evaluated for GBS), and cranial nerve palsies. Evaluate for evidence of HLH/MAS in patients with progressive CRS symptoms or refractory CRS despite treatment. Monitor for signs/symptoms of infection (before and after treatment), and hepatitis B reactivation. Monitor life-long for secondary malignancies (including myeloid neoplasms and T-cell malignancies). Monitor closely for 2 hours after infusion for signs/symptoms of severe hypersensitivity reaction.
Additional neurotoxicity monitoring recommendations (Cohen 2022): In patients with preexisting neurologic disease, consider baseline MRI and EEG and neurologic consultation. Evaluate at the first sign of neurotoxicity, including ICANS and raised intracranial pressure/cerebral edema; assess with new onset of headache, seizure, speech or visual disorders, disturbances in consciousness, confusion, disorientation, coordination/balance/movement disorders, mental status changes, cognitive impairment, and/or personality changes. Evaluate at first sign of neurotoxicity for infectious (eg, human herpes virus), autoimmune, or paraneoplastic/tumoral or metabolic etiologies in blood, cerebrospinal fluid, and/or radiologic imaging. Perform immune effector cell–associated encephalopathy assessment tool at baseline and at least daily after first symptoms of neurotoxicity (eg, ICANS or other neurotoxicities) are suspected; continue until resolution. Consider handwriting assessments for early detection of neurotoxicity symptoms. Consider extending neurotoxicity monitoring up to 1 year following ciltacabtagene autoleucel infusion.
The American Society of Clinical Oncology HBV screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]). Obtain baseline ECG, natriuretic peptides, and troponins; a baseline echocardiography is recommended in patients with preexisting cardiovascular disease; consider baseline echocardiography in all patients; for patients who develop ≥ grade 2 cytokine release syndrome, assess natriuretic peptides and troponins, and obtain echocardiography (ESC [Lyon 2022]). Refer to a cardiologist when clinically indicated.
Ciltacabtagene autoleucel is a B cell maturation antigen (BCMA)-directed genetically modified autologous T-cell immunotherapy in which a patient's T cells are reprogrammed via transduction with a lentiviral vector to express an anti-BCMA chimeric antigen receptor (CAR). The CAR T-cell construct includes an anti-BCMA targeting domain consisting of a CD3-zeta signaling domain and a 4-1BB costimulatory domain. Ciltacabtagene autoleucel is prepared from the patient’s peripheral blood mononuclear cells (obtained via leukapheresis), which are enriched for T cells. When infused back into the patient, the anti-BCMA CAR T cells recognize and eliminate BCMA-expressing target cells. In addition to T cells, ciltacabtagene autoleucel may contain natural killer (NK) cells.
Note: Ciltacabtagene autoleucel exhibits an initial rapid expansion followed by a rapid decline, and then a slower decline. Patients who received tocilizumab, corticosteroids, or anakinra to manage cytokine release syndrome (CRS) experienced higher ciltacabtagene autoleucel AUC0 to 28d and Cmax compared to patients who did not receive tocilizumab, corticosteroids, or anakinra.
Duration: The median time for chimeric antigen receptor transgene levels in peripheral blood to return to predose baseline level was ~100 to 109 days postinfusion (range: 28 to 366 days).
Distribution: Distributes into bone marrow (from systemic circulation).
Half-life elimination: Median half-life: 11.7 to 15.3 days (range: 3 to ~180 days).
Time to peak: Median time to maximal expansion (in peripheral blood): ~13 days after infusion.
