Miscellaneous antineoplastics
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Abecma Dosage

Drug Detail:Abecma ( idecabtagene vicleucel)

Generic Name: IDECABTAGENE VICLEUCEL 3000000001

Dosage Form: intravenous suspension

Drug Class: Miscellaneous antineoplastics

Contents
Uses Warnings Before Taking Dosage Side effects Interactions

For autologous use only. For intravenous use only.

Dose

ABECMA is provided as a single dose for infusion containing a suspension of chimeric antigen receptor (CAR)-positive T cells in one or more infusion bags. The recommended dose range is 300 to 460 × 106 CAR-positive T cells.

See the accompanying Release for Infusion Certificate (RFI Certificate) for additional information pertaining to dose [see How Supplied/Storage and Handling (16)].

Administration

ABECMA is for autologous use only. The patient's identity must match the patient identifiers on the ABECMA cassette(s) and infusion bag(s). Do not infuse ABECMA if the information on the patient-specific label(s) does not match the intended patient.

Preparing Patient for ABECMA Infusion

Confirm the availability of ABECMA prior to starting the lymphodepleting chemotherapy regimen.

Pretreatment

Administer the lymphodepleting chemotherapy regimen: cyclophosphamide 300 mg/m2 intravenously (IV) and fludarabine 30 mg/m2 IV for 3 days.

See the prescribing information of cyclophosphamide and fludarabine for information on dose adjustment in renal impairment.

Administer ABECMA 2 days after completion of lymphodepleting chemotherapy.

Delay the infusion of ABECMA up to 7 days if a patient has any of the following conditions:

•
unresolved serious adverse events (especially pulmonary events, cardiac events, or hypotension), including those after preceding chemotherapies
•
active infections or inflammatory disorders [see Warnings and Precautions (5.5)].

Premedication

Administer acetaminophen (650 mg orally) and diphenhydramine (12.5 mg IV or 25 to 50 mg orally, or another H1-antihistamine) approximately 30 to 60 minutes before infusion of ABECMA.

Avoid prophylactic use of dexamethasone or other systemic corticosteroids, as the use may interfere with the activity of ABECMA.

Receipt of ABECMA

•
ABECMA is shipped directly to the cell laboratory or clinical pharmacy associated with the infusion center in the vapor phase of a liquid nitrogen shipper.
•
Confirm the patient's identity with the patient identifiers on the shipper.
•
If the patient is not expected to be ready for same-day administration before the shipper expires and the infusion site is qualified for onsite storage, transfer ABECMA to onsite vapor phase of liquid nitrogen storage.
•
If the patient is not expected to be ready for same day administration before the shipper expires and the infusion site is not qualified for onsite storage, contact Bristol-Myers Squibb at 1-888-805-4555 to arrange for return shipment.

Preparation of ABECMA for Infusion

1.
Coordinate the timing of ABECMA thaw and infusion. Confirm the infusion time in advance and adjust the start time of the thaw of ABECMA so that it will be available for infusion when the patient is ready.
2.
Prior to thawing the product, confirm that tocilizumab and emergency equipment are available prior to the infusion and during the recovery period.
3.
An ABECMA dose may be contained in one or more patient-specific infusion bag(s). Verify the number of bags received for the indicated dose of ABECMA prior to preparation of ABECMA for infusion.
4.
Confirm patient identity: Prior to preparation of ABECMA, match the patient's identity with the patient identifiers on the ABECMA cassette(s), infusion bag(s), and the RFI Certificate.

Note: The patient identifier number may be preceded by the letters DIN or Aph ID.

5.
Do not remove the ABECMA infusion bag(s) from the cassette(s) if the information on the patient-specific cassette label(s) does not match the intended patient. Contact Bristol-Myers Squibb at 1-888-805-4555 if there are any discrepancies between the labels and the patient identifiers.
6.
Once patient identity is confirmed, remove the ABECMA infusion bag(s) from the cassette(s) and check that the patient information on the cassette label(s) matches the patient information on the bag label(s).

Figure 1: ABECMA Bag Label(s)
Figure 1
7.
Inspect the infusion bag(s) for any breaches of container integrity such as breaks or cracks before thawing. If the bag(s) is compromised, contact Bristol-Myers Squibb at 1-888-805-4555.
8.
If more than one infusion bag has been received to achieve the treatment dose, thaw each infusion bag one at a time. Do not initiate thaw of the next bag until infusion of the previous bag is complete.
9.
Place the infusion bag(s) inside a second sterile bag per local guidelines.
10.
Thaw ABECMA infusion bag(s) at approximately 37°C using an approved thaw device or water bath until there is no visible ice in the infusion bag. Gently mix the contents of the bag to disperse clumps of cellular material. If visible cell clumps remain, continue to gently mix the contents of the bag. Small clumps of cellular material should disperse with gentle manual mixing. Do not wash, spin down, and/or resuspend ABECMA in new media prior to infusion.
11.
ABECMA should be administered within 1 hour of the start of thaw. ABECMA is stable for 2 hours at room temperature once thawed.

ABECMA Administration

•
For autologous use only.
•
Do NOT use a leukodepleting filter.
•
Ensure that a minimum of 2 doses of tocilizumab and emergency equipment are available prior to infusion and during the recovery period.
•
Central venous access may be utilized for the infusion of ABECMA and is encouraged in patients with poor peripheral access.

1.
Confirm that the patient's identity matches the patient identifiers on the ABECMA infusion bag(s).
2.
Prime the tubing of the infusion set with normal saline prior to infusion.
3.
Infuse the entire contents of the ABECMA infusion bag within 1 hour after start of thaw by gravity flow.
4.
After the entire content of the infusion bag is infused, rinse the tubing with 30 to 60 mL of normal saline at the same infusion rate to ensure all product is delivered.
5.
If more than one infusion bag has been received, administer all bags as directed, following steps 1-4 for all subsequent infusion bags. Do not initiate thaw of the next bag until infusion of the previous bag is complete.

ABECMA contains human blood cells that are genetically modified with replication-incompetent, self-inactivating lentiviral vector. Follow universal precautions and local biosafety guidelines for handling and disposal of ABECMA to avoid potential transmission of infectious diseases.

Monitoring

•
Administer ABECMA at a REMS-certified healthcare facility.
•
Monitor patients at least daily for 7 days following ABECMA infusion at the certified healthcare facility for signs and symptoms of CRS and neurologic toxicities [see Warnings and Precautions (5.1, 5.2)].
•
Instruct patients to remain within proximity of the certified healthcare facility for at least 4 weeks following infusion.
•
Instruct patients to refrain from driving or hazardous activities for at least 8 weeks following infusion.

Management of Severe Adverse Reactions

Cytokine Release Syndrome (CRS)

Identify CRS based on clinical presentation [see Warnings and Precautions (5.1)]. Evaluate for and treat other causes of fever, hypoxia, and hypotension.

If CRS is suspected, manage according to the recommendations in Table 1.

Patients who experience CRS should be closely monitored for cardiac and organ function until resolution of symptoms. Consider antiseizure prophylaxis with levetiracetam in patients who experience CRS.

Patients who experience Grade 2 or higher CRS (e.g., hypotension not responsive to fluids, or hypoxia requiring supplemental oxygenation) should be monitored with continuous cardiac telemetry and pulse oximetry.

For severe or life-threatening CRS, consider intensive care unit level monitoring and supportive therapy.

For CRS refractory to first line interventions such as tocilizumab or tocilizumab and corticosteroids, consider alternate treatment options (i.e., higher corticosteroid dose, alternative anti-cytokine agents, anti-T cell therapies). Refractory CRS is characterized by fevers, end-organ toxicity (e.g., 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:

•
Corticosteroids according to the more aggressive intervention based on the CRS and neurologic toxicity grades in Tables 1 and 2
•
Tocilizumab according to the CRS grade in Table 1
•
Antiseizure medication according to the neurologic toxicity in Table 2
Table 1: CRS Grading and Management Guidance
CRS Gradea Tocilizumabc Corticosteroidsb
a Lee criteria for grading CRS (Lee et al., 2014).
b If corticosteroids are initiated, continue corticosteroids for at least 3 doses, and taper over a maximum of 7 days.
c Refer to tocilizumab Prescribing Information for details.

Grade 1
Symptoms require symptomatic treatment only (e.g., fever, nausea, fatigue, headache, myalgia, malaise).

If onset 72 hours or more after infusion, treat symptomatically.

If onset less than 72 hours after infusion, consider tocilizumab 8 mg/kg IV over 1 hour (not to exceed 800 mg).

Consider dexamethasone 10 mg IV every 24 hours.

Grade 2
Symptoms require and respond to moderate intervention.

Oxygen requirement less than 40% FiO2 or hypotension responsive to fluids, or low dose of one vasopressor, 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 or increasing supplemental oxygen.

Limit to a maximum of 3 doses in a 24-hour period; maximum total of 4 doses.

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 followed by 2 mg/kg divided 4 times per day.

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.

Fever, oxygen requirement greater than or equal to 40% FiO2, or hypotension requiring high-dose or multiple vasopressors, 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 followed by 2 mg/kg divided 4 times per day.

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), 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, repeat every 24 hours if needed; taper as clinically indicated) or other anti-T cell therapies.

Neurologic Toxicity

Monitor patients for signs and symptoms of neurologic toxicities (Table 2). Rule out other causes of neurologic signs or symptoms. Provide intensive care supportive therapy for severe or life-threatening neurologic toxicities. If neurologic toxicity is suspected, manage according to the recommendations in Table 2.

If concurrent CRS is suspected during the neurologic toxicity event, administer:

•
Corticosteroids according to the more aggressive intervention based on the CRS and neurologic toxicity grades in Tables 1 and 2
•
Tocilizumab according to CRS grade in Table 1
•
Antiseizure medication according to neurologic toxicity in Table 2
Table 2: Neurologic Toxicity Grading and Management Guidance
Neurologic Toxicity Gradea Corticosteroids and Antiseizure Medications
a NCI CTCAE criteria for grading neurologic toxicities version 4.03.

Grade 1

Start non-sedating, antiseizure medicines (e.g., levetiracetam) for seizure prophylaxis.
If 72 hours or more after infusion, observe patient.
If less than 72 hours after infusion, consider dexamethasone 10 mg IV every 12 to 24 hours for 2 to 3 days.

Grade 2

Start non-sedating, antiseizure medicines (e.g., levetiracetam) for seizure prophylaxis.
Start dexamethasone 10 mg IV every 12 hours for 2-3 days, or longer for persistent symptoms.
Consider taper for a total corticosteroid exposure of greater than 3 days. Corticosteroids are not recommended for isolated Grade 2 headaches.
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.

Grade 3

Start non-sedating, antiseizure medicines (e.g., levetiracetam) for seizure prophylaxis.
Start dexamethasone 10 to 20 mg IV every 6 to 12 hours. Corticosteroids are not recommended for isolated Grade 3 headaches.
If no improvement after 24 hours or worsening of neurologic toxicity, escalate to methylprednisolone (2 mg/kg loading dose, followed by 2 mg/kg divided into 4 times a day; taper within 7 days).
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) and cyclophosphamide 1.5 g/m2.

Grade 4

Start non-sedating, antiseizure medicines (e.g., levetiracetam) for seizure prophylaxis.
Start 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, repeated every 24 hours if needed; taper as clinically indicated).
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), and cyclophosphamide 1.5 g/m2.
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