Carvykti Dosing

Generic Name: Ciltacabtagene autoleucel

Dosage form: Suspension for intravenous infusion

Brand name: Carvykti

Medically reviewed by R Rash MD.  Updated on 23 Mar 2022.

What exactly is Carvykti?

Carvykti is a genetically engineered autologous T cell immunotherapy that is directed by BCMA. Carvykti is synthesized from the patient’s mononuclear cells in the peripheral blood, which is collected by a conventional leukapheresis process. The mononuclear cells are enriched for T cells and genetically modified ex vivo using a replication-incompetent lentiviral vector to express a chimeric antigen receptor (CAR) with an anti-BCMA targeting domain made up of two single-domain antibodies linked to a 4-1BB costimulatory domain and a CD3-zeta signaling domain.

Anti-BCMA CAR T cells that have been transduced are grown in cell culture, washed, formed into a suspension, and cryopreserved. Before being shipped as a frozen suspension in a patient-specific infusion bag, the product must pass a sterility test. The anti-BCMA CAR T cells are frozen and injected back into the patient, where they may recognize and eradicate BCMA-expressing target cells.

Carvykti may contain Natural Killer (NK) cells in addition to T cells. Dimethyl sulfoxide (DMS) is present in the formulation at a concentration of 5%. (DMSO).

Important information

Carvykti could cause adverse reactions that are serious or life-threatening and could cause death. Consult your physician or seek emergency assistance right immediately if you experience any of the following symptoms:

It is crucial to inform your healthcare provider that you’ve received Carvykti and also present them with your Carvykti Patient Card for Wallet. Your healthcare provider could give you additional medications to manage your symptoms.

Warnings and Precautions

Before you get Carvykti

Before receiving Carvykti, tell your doctor about your medical condition such as if you suffer from:

Carvykti Dosing

CARVYKTI is offered in single-dose infusions that contain a suspension of antigen receptors chimeric (CAR)-positive T cells that are viable in a single infusion bag.

The recommended dosage interval is 0.5-1.0×106 CAR-positive T cells per kilogram of body weight. There is a maximum dose being 1×108 CAR-positive viable T cell for a single injection.

Administration

CARVYKTI is intended for use by autologous patients only. The patient’s name must match the patient’s identifiers that are on the CARVYKTI cassette and the infusion bag. Do not inject CARVYKTI when the information printed on the labels for patients is not in line with the intention of the patient.

The Patient is prepared to receive CARVYKTI Infusion

Check for CARVYKTI’s availability prior to beginning the chemotherapy regimen that is lymphodepleting.

Pretreatment

Apply the lymphodepleting chemotherapy regimen for the following regimen: cyclophosphamide 300 mg/m2 intravenous(IV) along with fludarabine 30, mg/m2 intravenously (IV) daily for 3 consecutive days.

Check the prescribing instructions for fludarabine and cyclophosphamide for details regarding dose adjustments for renal impairment.

The lymphodepleting treatment should be delayed in the event that the patient is suffering from serious adverse reactions from previous treatments for bridging (including significant clinically-significant active infection and cardiac toxicity, as well as toxic pulmonary reactions) and active graft against host disease in a patient who has had an allogeneic stem cell transplant prior to. It is recommended to repeat the lymphodepleting procedure when CARVYKTI dosage is delayed over 14 days, and the patient is recovering from the toxic effects of the initial lymphodepleting regimen.

Infusions of CARVYKTI are administered between 2 and 4 days following the end of the chemotherapy regimen for lymphodepleting.

CARVYKTI infusions must be delayed in patients who suffer from any of the following ailments:

  • Active infection that is clinically significant or inflammation disorders.
  • Grade >=3 non-hematologic toxicities from fludarabine conditioning and cyclophosphamide with the exception of diarrhea, nausea, vomiting, or constipation. CARVYKTI infusions should be delayed until these conditions have resolved until Grade =1.

Premedication

Pre-infusion medication: Administer the following to all patients for 30 to sixty minutes before CARVYKTI infusion:

  • The antipyretics (oral or intravenous oral acetaminophen (650 or 1000 mg).
  • Antihistamine (oral or intravenous diphenhydramine between 25 and 50 mg and equivalent).

Do not use prophylactically corticosteroids for systemic use, since their use could affect the action of CARVYKTI.

Receipt of CARVYKTI

  • All infusion sites that are approved can meet the requirements for storage for the vapor phase of liquid nitrogen.
  • CARVYKTI is delivered directly to the laboratory for cell research or the clinical pharmacy that is associated with the infusion center in the liquid phase of a nitrogen shipper.
  • Verify the identity of the patient by using the patient’s identifiers on the shipping label.
  • If the patient isn’t likely to be ready for the same day administration prior to when the expiration date of the shipper then transfers CARVYKTI into the liquid nitrogen storage.

The preparation Of CARVYKTI for Infusion

Do not freeze the product until it’s ready for use. Set the time for CARVYKTI freezing and infusion. In the event of an infusion, confirm the timing ahead of time and alter the time to begin thawing to ensure that CARVYKTI is ready for infusion at the time that the patient is in the right position. After thawing it is time to administer the CARVYKTI infusion should complete within 2.5 hours at room temperature (20degC to 25degC).).

Before thawing the frozen product, ensure that tocilizumab and other emergency equipment is available prior to the infusion as well as during the recovery time.

  1. Verify the identity of the patient prior in the course of CARVYKTI preparation, verify your patient’s name to the patient’s identification numbers in the CARVYKTI cassette. Do not take your CARVYKTI Infusion Bag from the cassette in the event that the information on the label for the patient does not match that of the intended patient. Please contact Janssen Biotech, Inc. at 1-800-526-7736 in the event of any differences in the labeling and patients’ identifiers.
  2. If the identification of the patient is confirmed, take from the CARVYKTI bags from cassettes and verify that the information for the patient on the label on the cassette is the same as the information for the patient on the bag’s label.
  3. Examine the bag for any signs in the integrity of the bag for example, cracks or fractures prior to the freezing. Do not give the medication the product if the bag has been damaged or damaged, and then contact Janssen Biotech, Inc. at 1-800-526-7736.
  4. Place the infusion container in the bag that is sealable (preferably sterilized) before the process of thawing.
  5. Thaw CARVYKTI in 37degC+2degC with either an infusion bath or dry-thaw technique until there is no evidence of any ice left in the infusion bag. The total time from the beginning of thawing until the end of thawing must not be longer than fifteen minutes.
  6. Take the infusion bag out of the bag with a seal and clean it. The contents should be mixed gently in the bag until you can disperse clumps of cellular matter. In the event that visible cell clumps persist Continue to mix with the contents of the bag. Small clumps of cell material will disperse by gentle mixing. Don’t pre-filter in another container or wash, spin down or refrigerate CARVYKTI in a fresh medium ahead of infusion.
  7. Do not refrigerate or re-freeze the frozen item that has been thawed.

Administration

  • Only for autologous injections.
  • Do NOT use a leukocyte-depleting filter.
  • Make sure that at least two doses of the drug tocilizumab and emergency equipment is ready prior to the infusion and during the recovery time.
  • Central venous access can be used for the administration of CARVYKTI and is suggested for patients who have difficulty with peripheral access.
  1. Verify the identity of the patient by using the patient’s identification numbers that are on the inside of the infusion bags. Don’t infuse CARVYKTI in the event that the information on the label specifically for the patient is not in line with the intention of the patient.
  2. Clean the tubing of the set by using normal saline prior to the infusion.
  3. After thawing, give the items in the CARVYKTI bag through intravenous injection within 2.5 hours using infusion kits equipped with an in-line filter.
  4. Mix all the ingredients of your bag throughout CARVYKTI infusion to break up cell clumps.
  5. Once the complete contents of the bag have been infused and the administration line is flushed and the filter in-line, with normal saline in a quantity that is equal to or greater than the volume of the hold-up of the main administration set, which includes the drip tube, in order to make sure that the entire product is being delivered.

CARVYKTI contains human blood cells that are genetically modified with replication-incompetent, self-inactivating, lentiviral vector. Be sure to follow the universal precautions and local guidelines for biosafety the handling and disposal of CARVYKTI to prevent the transmission of infectious diseases.

Monitoring Following Infusion

Take CARVYKTI in a healthcare facility that is certified by REMS. facility.

Be sure to monitor patients daily for 10 days after CARVYKTI infusions in an accredited healthcare facility for symptoms and signs of cytokine release syndrome (CRS) or neurologic toxicities. Keep an eye on patients regularly for four weeks to look for signs and symptoms of neurologic toxicity that is delayed.

Inform patients to stay within the vicinity of a health facility for at least four weeks following the infusion.

Remind patients to abstain from driving or performing hazardous activities for at least 8 weeks after the infusion.

Management of severe adverse reactions

Cytokine Release Syndrome

Recognize CRS based on symptoms in the clinical setting. Assess and treat other reasons for hypertension, hypoxia, and fever. Examine laboratory tests to look for disseminated intravascular blood coagulation, Hematology parameters, as well for cardiac, pulmonary, renal and hepatic functions. If you suspect CRS, follow the guidelines in Table 1.

Patients with CRS must be monitored closely for heart and other organ functions until the symptoms are gone. Look into anti-seizure medication using levetiracetam for patients who have CRS.

Patients with CRS of Grade 2 or greater (e.g. hypotension that isn’t sensitive to fluids or hypoxia that requires supplemental oxygenation) must be monitored using continuous telemetry as well as pulse oximetry.

If you have a life-threatening or severe case of CRS, you should consider the intensive care unit level of monitoring and therapy for support needs.

If CRS is resistant to treatment options of the first line such as tocilizumab corticosteroids and tocilizumab, think about alternative treatment options (i.e. an increase in corticosteroid dose, or alternative anti-cytokine therapies, e.g., anti-IL1 or anti-TNFa and/or anti-T cells treatments). Refractory CRS is characterized by symptoms of fevers, end-organ toxicities (e.g. hypotension, hypoxia) that do not improve within 12 hours following the first-line treatment or the development of HLH/MAS.

If concurrent neurologic toxicities are suspected in CRS, you should administer:

  • Corticosteroids based on the most aggressive treatment based on the CRS as well as neurologic toxicity ratings in Tables 1 & 2
  • Tocilizumab as per the CRS grade as listed in Table 1
  • Anti-seizure medicine based on the neurologic toxicity of Table 2.

Table 1

CRS Grade* Tocilizumab† Corticosteroids‡
Grade 1
Temperature ≥38°C§ In patients with:

·     Early onset of fever (if onset less than 72 hours after infusion)

Tocilizumab 8 mg/kg intravenously (IV) over 1 hour (not to exceed 800 mg) may be considered

N/A
Grade 2
Symptoms require and respond to moderate intervention.
Temperature ≥38°C§ with:
Hypotension not requiring vasopressors,
and/or,
Hypoxia requiring oxygen via canulaÞ or blow-by,
or,
Grade 2 organ toxicity.
Administer tocilizumab 8 mg/kg IV over 1 hour (not to exceed 800 mg).
Repeat tocilizumab every 8 hours as needed if not responsive to intravenous fluids up to 1 liter or increasing supplemental oxygen.
Consider dexamethasone 10 mg IV every 12–24 hours.
If no improvement within 24 hours or rapid progression, repeat tocilizumab and escalate dose and frequency of dexamethasone (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 doses of tocilizumab, consider alternative anti-cytokine agents.#
Do not exceed 3 doses of tocilizumab in 24 hours, or 4 doses in total.
Grade 3
Symptoms require and respond to aggressive intervention.
Temperature ≥38°C§ with:
Hypotension requiring one vasopressor with or without vasopressin,
and/or,
Hypoxia requiring oxygen via high-flow nasal canulaÞ, facemask, non-rebreather mask, or Venturi mask,
or,
Grade 3 organ toxicity or Grade 4 transaminitis.
Per Grade 2 Administer dexamethasone 10 mg IV every 12 hours.
If no improvement within 24 hours or rapid progression, repeat tocilizumab and escalate dose and frequency of dexamethasone (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 doses of tocilizumab, consider alternative anti-cytokine agents.#
Do not exceed 3 doses of tocilizumab in 24 hours, or 4 doses in total.
Grade 4
Life-threatening symptoms.
Requirements for ventilator support, continuous veno-venous hemodialysis (CVVHD).
Temperature ≥38°C§ with:
Hypotension requiring multiple vasopressors (excluding vasopressin),
and/or,
Hypoxia requiring positive pressure (e.g., CPAP, BiPAP, intubation, and mechanical ventilation),
or,
Grade 4 organ toxicity (excluding transaminitis).
Per Grade 2 Administer dexamethasone 20 mg IV every 6 hours.
After 2 doses of tocilizumab, consider alternative anti-cytokine agents#. Do not exceed 3 doses of tocilizumab in 24 hours, or 4 doses in total.
If no improvement within 24 hours, consider methylprednisolone (1–2 g IV, repeat every 24 hours if needed; taper as clinically indicated) or other immunosuppressants (e.g. other anti-T cell therapies).

 

  • * Based on ASTCT 2019 grading system (Lee et.al, 2019), modified to include organ toxicity.
  • † Refer to tocilizumab prescribing information for details.
  • ‡ Continue corticosteroids use until the event is Grade 1 or less; taper steroids if total corticosteroid exposure is greater than 3 days.
  • § Attributed to CRS. Fever may not always be present concurrently with hypotension or hypoxia, as it may be masked by interventions such as antipyretics or anti-cytokine therapy (e.g., tocilizumab or steroids). Absence of fever does not impact CRS management decision. In this case, CRS management is driven by hypotension and/or hypoxia and by the more severe symptom not attributable to any other cause.
  • ¶ Organ toxicity grading based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.#Monoclonal antibodies targeting cytokines may be considered based on institutional practice for unresponsive CRS.
  • Þ Low-flow nasal cannula is ≤6 L/min; high-flow nasal cannula is >6 L/min.

 

Neurologic Toxicities

Examine patients for symptoms and signs that indicate neurologic toxicities (ICANS or other neurologic toxicities) (Table 2.). Find other possible causes for neurological signs or symptoms. Offer intensive care and therapy with a supportive approach for serious dangerous neurologic poisoning. When ICANS may be suspected, address the issue with the advice in Table 2.

If CRS may be concurrently present in the neurologic toxicity event If so, you should treat:

  • Corticosteroids are based on the most aggressive treatment determined by the CRS and neurologic toxicity ratings in Tables 1 and 2.
  • Tocilizumab in accordance with the CRS grade listed in Table 1.
  • Anti-seizure medications based on neurologic toxicity as shown in Table 2.

Table: 2

ICANS Grade* Corticosteroids
Grade 1
ICE score 7–9
or depressed level of consciousness: awakens spontaneously.
Consider dexamethasone 10 mg IV every 12 to 24 hours for 2 to 3 days.
Consider non-sedating, anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis.
Grade 2
ICE score-3–6
or depressed level of consciousness: awakens to voice
Administer dexamethasone 10 mg IV every 12 hours for 2–3 days, or longer for persistent symptoms.
Consider steroid taper if total corticosteroid exposure is greater than 3 days.
If no improvement after 24 hours or worsening of neurologic toxicity, increase the dose and/or frequency of dexamethasone up to a maximum of 20 mg IV every 6 hours.
Consider non-sedating, anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis.
Grade 3
ICE score-0–2
(If ICE score is 0, but the patient is arousable (e.g., awake with global aphasia) and able to perform assessment)
or depressed level of consciousness: awakens only to tactile stimulus,
or seizures, either:·    any clinical seizure, focal or generalized, that resolves rapidly, or

·    non-convulsive seizures on EEG that resolve with intervention,

or raised intracranial pressure (ICP): focal/local edema on neuroimaging§.

Administer dexamethasone 10 mg-20 mg IV every 6 hours.
If no improvement after 24 hours or worsening of neurologic toxicity, escalate dexamethasone dose to at least 20 mg IV every 6 hours,
OR escalate to high-dose methylprednisolone (1–2 g/day, repeat every 24 hours if needed; taper as clinically indicated)
Consider non-sedating, anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis.
If cerebral edema is suspected, consider hyperventilation and hyperosmolar therapy. Give high-dose methylprednisolone (1–2 g, repeat every 24 hours if needed; taper as clinically indicated).
Grade 4
ICE score-0 (Patient is unarousable and unable to perform ICE assessment)
or depressed level of consciousness either:·    patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse, or

·    stupor or coma,

or seizures, either:

·    life-threatening prolonged seizure (>5 min), or

·    repetitive clinical or electrical seizures without return to baseline in between,

or motor findings:

·    deep focal motor weakness such as hemiparesis or paraparesis,

or raised ICP/cerebral edema, with signs/symptoms such as:

·    diffuse cerebral edema on neuroimaging, or

·    decerebrate or decorticate posturing, or

·    cranial nerve VI palsy, or

·    papilledema, or

·    Cushing’s triad

Administer dexamethasone 20 mg IV every 6 hours.
If no improvement after 24 hours or worsening of neurologic toxicity, escalate to high-dose methylprednisolone (1–2 g/day, repeated every 24 hours if needed; taper as clinically indicated).
Consider non-sedating, anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis.
If raised ICP/cerebral edema is suspected, consider hyperventilation and hyperosmolar therapy. Give high-dose methylprednisolone (1–2 g/day, repeat every 24 hours if needed; taper as clinically indicated), and consider neurology and/or neurosurgery consultation.

Note: ICANS grade and management is determined by the most severe event (ICE score, level of consciousness, seizure, motor findings, raised ICP/cerebral edema), not attributable to any other cause.

* ASTCT 2019 criteria for grading Neurologic Toxicity (Lee et.al, 2019).
† If patient is arousable and able to perform Immune Effector Cell-Associated Encephalopathy (ICE) Assessment, assess Orientation (oriented to year, month, city, hospital = 4 points); Naming (name 3 objects, e.g., point to clock, pen, button = 3 points); Following Commands (e.g., “show me 2 fingers” or “close your eyes and stick out your tongue” = 1 point); Writing (ability to write a standard sentence = 1 point); and Attention (count backwards from 100 by ten = 1 point). If the patient is unarousable and unable to perform ICE Assessment (Grade 4 ICANS) = 0 points.
‡ All references to dexamethasone administration are dexamethasone or equivalent.
§ Intracranial hemorrhage with or without associated edema is not considered a neurotoxicity feature and is excluded from ICANS grading. It may be graded according to NCI CTCAE v5.0.
¶ Tremors and myoclonus associated with immune effector cell therapies may be graded according to NCI CTCAE v5.0, but they do not influence ICANS grading.

Label

70 ml label

  • Ciltacabtagene autoleucel
    CARVYKTI
  • Suspension for Intravenous Infusion
  • Dose: One sterile bag for infusion.
  • Storage: Store and transport in a vapor phase of
    liquid nitrogen ≤ -120°C (-184°F). Thaw before using.
  • Rx only
Carvykti Dosing

30 ml Label

  • Ciltacabtagene autoleucel
  • CARVYKTI™
  • Suspension for Intravenous Infusion
  • Dose: One sterile bag for infusion.
  • Rx only

 

Carvykti Dosing

Additional details

Always consult your doctor to make sure the information presented on this page is applicable to your particular situation.

 

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