Abecma

/ Bristol Myers Squibb (Israel) Ltd.

A minimum of one dose of tocilizumab for use in the event of cytokine release syndrome (CRS) and emergency equipment must be available prior to infusion. The treatment centre must have access to an additional dose of tocilizumab within 8 hours of each previous dose. In the exceptional case where tocilizumab is not available, suitable alternative measures to treat CRS instead of tocilizumab must be available prior to infusion.
Recommended Dosage: Adults: A single dose for infusion containing a target of 420 X 10^6 CAR-positive viable T cells, within a range of 260 to 500 X 10^6 CAR-positive viable T cells.
Administration: For intravenous use only. Administer as quickly as tolerated by gravity flow within 1 hour from the start of thaw. A leukodepleting filter must NOT be used.
Pre-treatment & Premedication:
Lymphodepleting chemotherapy: Cyclophosphamide 300 mg/m^2/day IV and fludarabine 30 mg/m^2/day IV for 3 days. The medicinal product is administered 2 to 9 days after completion of this regimen. If there is a delay in infusion of more than 9 days, then the patient should be re-treated with lymphodepleting chemotherapy after a minimum of 4 weeks from last lymphodepleting chemotherapy prior to receiving this medical product.
Premedication: Paracetamol (500 to 1,000 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. Prophylactic systemic corticosteroids should be avoided. Therapeutic doses of corticosteroids should be avoided 72 hours prior to the start of lymphodepleting chemotherapy and following infusion of this medical product except for the management of CRS, neurologic toxicities and other life-threatening emergencies
Preparation: Confirm the patient’s identity matches the infusion bag and Release for Infusion Certificate (RfIC). Thaw the product prior to administration; rinse tubing with sodium chloride 9 mg/mL (0.9%) after infusion to ensure all cells are administered.
Monitoring: Monitor vital signs prior to, every 10 minutes during, and every hour for 3 hours after infusion for hypersensitivity.
Monitor for signs of CRS, neurologic events, and other toxicities for at least 10 days at the treatment centre. Follow-up patients must remain within 2 hours of the centre for at least 4 weeks post-infusion.
Monitor vital signs prior to, every 10 minutes during, and every hour for 3 hours after infusion for hypersensitivity.
See prescribing information for full details.

Treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior therapies (including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody) and demonstrated disease progression on the last therapy.

* Hypersensitivity to the active substance or any excipient
* Contraindications of the lymphodepleting chemotherapy must be considered

Reasons to delay treatment
Due to the risks associated with treatment, infusion should be delayed 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 (including pneumonitis, myocarditis or hepatitis).
* Active graft-versus-host disease (GVHD).
Concomitant disease: Patients with active central nervous system (CNS) disorder or inadequate renal, hepatic, pulmonary or cardiac function are likely to be more vulnerable to the consequences of the adverse reactions and require special attention.
Prior allogeneic stem cell transplantation: It is not recommended that patients receive this medical product within 4 months after an allogeneic stem cell transplant (SCT) because of the potential risk of worsening GVHD. Leukapheresis for CAR‑T cell manufacturing should be performed at least 12 weeks after allogeneic stem cell transplantation.
Cytokine release syndrome: Fatal or life-threatening reactions occurred; identify based on clinical presentation (fever, hypoxia, hypotension). In clinical studies, the median time to onset of CRS was 1 day (range: 1 to 17). CRS has been reported to be associated with findings of haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) and the physiology of the syndromes may overlap. MAS is a potentially life-threatening condition, and patients should be closely monitored for evidence of MAS. Treatment of MAS should be administered per institutional guidelines. Ensure tocilizumab and emergency equipment are available.
Neurologic Toxicities: Severe or life-threatening ICANS (immune effector cell-associated neurotoxicity syndrome), aphasia, or encephalopathy may occur. The median time to onset of the first event of neurotoxicity was 3 days.
Prolonged Cytopenias: Patients may exhibit Grade 3 or 4 neutropenia or thrombocytopenia for several weeks. Blood counts should be monitored prior to and after infusion.
Infections: Do not administer to patients with active infections. Severe viral (e.g., CMV, HBV), bacterial, or fungal infections have occurred. Febrile neutropenia was observed in patients after infusion and may be concurrent with CRS. Monitor patients for signs and symptoms of infections after treatment and treat appropriately, if needed.
Hypogammaglobulinaemia: Plasma cell aplasia and hypogammaglobulinaemia can occur. Immunoglobulin levels should be monitored after treatment and managed per institutional guidelines including infection precautions, antibiotic or antiviral prophylaxis and immunoglobulin replacement.
Secondary malignancies including of T-cell origin: Patients treated with this medical product may develop secondary malignancies. T -cell malignancies have been reported following treatment of haematological malignancies with a BCMA- or CD19-directed CAR T-cell therapy. T-cell malignancies, including CAR-positive malignancies, have been reported within weeks and up to several years following administration of a CD19- or BCMA-, directed CAR T-cell therapy. There have been fatal outcomes. Patients should be monitored life-long for secondary malignancies. In the event that a secondary malignancy of T-cell origin occurs, the company should be contacted to obtain instructions on the collection of tumour samples for testing.
Hypersensitivity reactions: Allergic reactions may occur with the infusion. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO), an excipient. Patients not previously exposed to DMSO should be observed closely. Vital signs (blood pressure, heart rate, and oxygen saturation) and the occurrence of any symptom should be monitored prior to the start of the infusion, approximately every ten minutes during the infusion and every hour, for 3 hours, after the infusion.
See prescribing information for full details.

Very Common: CRS, neutropenia, anaemia, thrombocytopenia, , Febrile neutropenia, hypophosphataemia, diarrhoea, leukopenia, hypokalaemia, fatigue, nausea, lymphopenia, pyrexia, infections, headache, hypocalcaemia, hypomagnesaemia, arthralgia, hyponatraemia, hypoalbuminaemia, decreased appetite, insomnia, encephalopathy, dizziness, tachycardia, hypertension, hypotension, dyspnoea, cough, vomiting, constipation, oedema, chills, increased ALT/AST, hypogammaglobulinaemia,
Common: Infections (fungal), disseminated intravascular coagulation, delirium, aphasia, ataxia, motor dysfunction, tremor, atrial fibrillation, pulmonary oedema, hypoxia, gastrointestinal haemorrhage, myalgia, asthenia, increased blood alkaline phosphatase, and increased C-reactive protein, haemophagocytic lymphohistiocytosis (HLH), seizure
See prescribing information for full details.

No interaction studies performed. Co-administration of agents inhibiting or stimulating T-cell function has not been studied. Vaccination with live vaccines is not recommended for at least 6 weeks prior to chemotherapy, during treatment, and until immune recovery.
See prescribing information for full details.

Pregnancy: No human data available. Not recommended for women who are pregnant or of childbearing potential not using contraception.
Lactation: It is unknown if cells are excreted in human milk; a risk to the breast-fed infant cannot be excluded.

Major influence on the ability to drive and use machines. Refrain from driving or operating heavy machines for at least 8 weeks after infusion or until resolution of neurologic symptoms.
Must remain frozen (at temperatures <130°C in the vapour phase of liquid nitrogen until thawed for use, stable for 12 months. After thawing, the volume of the product intended for infusion should be kept at room temperature (20°C – 25°C).