Dosage & Administration
For autologous use only. For intravenous use only.
Abecma Prescribing Information
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- Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with ABECMA. Do not administer ABECMA to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids [see Dosage and Administration (2.2, 2.3), Warnings and Precautions (5.2)].
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- Neurologic toxicities, which may be severe or life-threatening, occurred following treatment with ABECMA, including concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with ABECMA. Provide supportive care and/or corticosteroids as needed [see Dosage and Administration (2.2, 2.3) and Warnings and Precautions (5.3)].
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- Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS) including fatal and life-threatening reactions, occurred in patients following treatment with ABECMA. HLH/MAS can occur with CRS or neurologic toxicities [see Warnings and Precautions (5.4)].
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- Prolonged Cytopenia with bleeding and infection, including fatal outcomes following stem cell transplantation for hematopoietic recovery, occurred following treatment with ABECMA [see Warnings and Precautions (5.7)].
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- T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including ABECMA [see Warnings and Precautions (5.9)].
ABECMA is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma after two or more prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.
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 510 × 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 three days.
See the prescribing information of cyclophosphamide and fludarabine for information on dose adjustment in renal impairment.
Administer ABECMA two days after completion of lymphodepleting chemotherapy.
Delay the infusion of ABECMA up to seven days if a patient has any of the following conditions:
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- unresolved serious adverse events (especially pulmonary events, cardiac events, or hypotension), including those after preceding chemotherapies.
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- active infections or inflammatory disorders [see Warnings and Precautions (5.6)].
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
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- 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.
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- Confirm the patient's identity with the patient identifiers on the shipper.
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- 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.
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- 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) | |
 |
- 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, do not administer and 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 visible clumps of cellular material. Small clumps of cellular material may persist despite gentle manual mixing. Do not wash, spin down, and/or resuspend ABECMA in new media prior to infusion.
- 11.
- ABECMA should be administered within one hour of the initiation of the thaw process. ABECMA is stable for two hours at room temperature once thawed.
ABECMA Administration
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- For autologous use only.
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- Do NOT use a leukodepleting filter.
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- Confirm tocilizumab and emergency equipment are available prior to infusion and during the recovery period.
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- 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. An infusion set with an in-line filter (non-leukodepleting filter with a pore size range of 170 to 260 µm) can be used for thawed products with visible clumps of cellular material that do not disperse after gentle manual mixing.
- 3.
- Infuse the entire contents of the ABECMA infusion bag within one hour after start of thaw by gravity flow.
- 4.
- After the entire content of the infusion bag is infused, rinse the tubing, inclusive of the in-line filter if used, with 30 to 60 mL of normal saline at the same infusion rate to ensure as many cells as possible are infused into the patient.
- 5.
- If more than one infusion bag is received, administer all bags as directed, following steps 1-4 for each bag. 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
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- Monitor patients at least daily for seven days following ABECMA infusion for signs and symptoms of CRS and neurologic toxicities [see Warnings and Precautions (5.2, 5.3)].
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- Instruct patients to remain within proximity of a healthcare facility for at least two weeks following infusion.
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- Advise patients to avoid driving for at least 2 weeks following infusion.
Management of Severe Adverse Reactions
Cytokine Release Syndrome (CRS)
Identify CRS based on clinical presentation [see Warnings and Precautions (5.2)]. Evaluate for and treat other causes of fever, hypoxia, and hypotension.
If CRS is suspected, manage according to the recommendations in Table 1. Physicians may also consider management per current practice guidelines.
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:
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- Corticosteroids according to the more aggressive intervention based on the CRS and neurologic toxicity grades in Tables 1 and 2
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- Tocilizumab according to the CRS grade in Table 1
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- Antiseizure medication according to the neurologic toxicity in Table 2
| 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 seven days. c Refer to tocilizumab Prescribing Information for details. | ||
Grade 1 | 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 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). 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. | ||
Grade 3 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). 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 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. Physicians may also consider management per current practice guidelines.
If concurrent CRS is suspected during the neurologic toxicity event, administer:
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- Corticosteroids according to the more aggressive intervention based on the CRS and neurologic toxicity grades in Tables 1 and 2
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- Tocilizumab according to CRS grade in Table 1
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- Antiseizure medication according to neurologic toxicity in Table 2
| 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. |
Grade 2 | Start non-sedating, antiseizure medicines (e.g., levetiracetam) for seizure prophylaxis. |
Grade 3 | Start non-sedating, antiseizure medicines (e.g., levetiracetam) for seizure prophylaxis. |
Grade 4 | Start non-sedating, antiseizure medicines (e.g., levetiracetam) for seizure prophylaxis. |
ABECMA is a cell suspension for intravenous infusion.
A single dose of ABECMA contains a cell suspension of 300 to 510 × 106 chimeric antigen receptor (CAR)-positive T cells in one or more infusion bags [see How Supplied/Storage and Handling (16)].
Pregnancy
Risk Summary
There are no available data with ABECMA use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with ABECMA to assess whether it can cause fetal harm when administered to a pregnant woman.
It is not known if ABECMA has the potential to be transferred to the fetus. Based on the mechanism of action, if the transduced cells cross the placenta, they may cause fetal toxicity, including plasma cell aplasia or hypogammaglobulinemia. Therefore, ABECMA is not recommended for women who are pregnant, and pregnancy after ABECMA infusion should be discussed with the treating physician. Assess immunoglobulin levels in newborns of mothers treated with ABECMA.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. The estimated background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.
Lactation
Risk Summary
There is no information regarding the presence of ABECMA in human milk, the effect on the breastfed infant, and the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ABECMA and any potential adverse effects on the breastfed infant from ABECMA or from the underlying maternal condition.
Females and Males of Reproductive Potential
Pregnancy Testing
Pregnancy status of sexually active females with reproductive potential should be verified via pregnancy testing prior to starting treatment with ABECMA.
Contraception
See the prescribing information for fludarabine and cyclophosphamide for information on the need for effective contraception in patients who receive the lymphodepleting chemotherapy.
There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with ABECMA.
Infertility
There are no data on the effect of ABECMA on fertility.
Pediatric Use
The safety and efficacy of ABECMA in patients under 18 years of age have not been established.
Geriatric Use
In the clinical trials of ABECMA, 141 (40%) of the 349 patients were 65 years of age or older and 16/349 (4.6%) patients were 75 years of age or older. In KarMMa study, all five cases of Grade 3 neurotoxicity occurred in patients ≥ 65 years of age (66 to 74 years). No clinically important differences in effectiveness of ABECMA were observed between these patients and patients younger than 65 years of age.
None.