Idecabtagene Vicleucel
FDA Drug Information • Also known as: Abecma
- Brand Names
- Abecma
- Route
- INTRAVENOUS
- Dosage Form
- SUSPENSION
- Product Type
- CELLULAR THERAPY
⚠ Boxed Warning (Black Box)
WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, PROLONGED CYTOPENIA, AND SECONDARY HEMATOLOGICAL MALIGNANCIES
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) ] . 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) ] . 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) ] . 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) ] . 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) ] . WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, PROLONGED CYTOPENIA, AND SECONDARY HEMATOLOGICAL MALIGNANCIES See full prescribing information for complete boxed warning. 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. ( 2.2 , 2.3 , 5.2 ) 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. ( 2.2 , 2.3 , 5.3 ) 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. ( 5.4 ) Prolonged Cytopenia with bleeding and infection, including fatal outcomes following stem cell transplantation for hematopoietic recovery, occurred following treatment with ABECMA. ( 5.7 ) T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including ABECMA. ( 5.9 )Description
11 DESCRIPTION ABECMA is a BCMA-directed genetically modified autologous T cell immunotherapy product consisting of a patient's own T cells that are harvested and genetically modified ex vivo through transduction with an anti-BCMA02 chimeric antigen receptor (CAR) lentiviral vector (LVV). Autologous T cells transduced with the anti-BCMA02 CAR LVV express the anti-BCMA CAR on the T cell surface. The CAR is comprised of a murine extracellular single-chain variable fragment (scFv) specific for recognizing B cell maturation antigen (BCMA) followed by a human CD8α hinge and transmembrane domain fused to the T cell cytoplasmic signaling domains of CD137 (4-1BB) and CD3ζ chain, in tandem. Binding of ABECMA to BCMA-expressing target cells leads to signaling initiated by CD3ζ and 4-1BB domains, and subsequent CAR-positive T cell activation. Antigen-specific activation of ABECMA results in CAR-positive T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells. ABECMA is prepared from the patient's peripheral blood mononuclear cells (PBMCs), which are obtained via a standard leukapheresis procedure. The mononuclear cells are enriched for T cells, through activation with anti-CD3 and anti-CD28 antibodies in the presence of IL-2, which are then transduced with the replication-incompetent lentiviral vector containing the anti-BCMA CAR transgene. The transduced T cells are expanded in cell culture, washed, formulated into a suspension, and cryopreserved. The product must pass a sterility test before release for shipping as a frozen suspension in one or more patient-specific infusion bag(s). The product is thawed prior to infusion back into the patient [see Dosage and Administration (2.3) and How Supplied/Storage and Handling (16) ] . The ABECMA formulation contains 50% Plasma-Lyte A and 50% CryoStor ® CS10, resulting in a final DMSO concentration of 5%.
What Is Idecabtagene Vicleucel Used For?
1 INDICATIONS AND USAGE ABECMA is 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. 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. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION For autologous use only. For intravenous use only.
Do NOT use a leukodepleting filter. ( 2.2 ) Administer a lymphodepleting chemotherapy regimen of cyclophosphamide and fludarabine before infusion of ABECMA. ( 2.2 ) Confirm the patient's identity prior to infusion. ( 2.2 ) Premedicate with acetaminophen and an H 1 -antihistamine. ( 2.2 ) Avoid prophylactic use of dexamethasone or other systemic corticosteroids. ( 2.2 ) Confirm availability of tocilizumab prior to infusion. ( 2.2 , 5.2 ) Dosing of ABECMA is based on the number of chimeric antigen receptor (CAR)-positive T cells. ( 2.1 ) The recommended dose range is 300 to 510 × 10 6 CAR-positive T cells. ( 2.1 ) 2.1 Dose For autologous use only. For intravenous use only. 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 × 10 6 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) ] . 2.2 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/m 2 intravenously (IV) and fludarabine 30 mg/m 2 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: 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 (5.6) ] . Premedication Administer acetaminophen (650 mg orally) and diphenhydramine (12.5 mg IV or 25 to 50 mg orally, or another H 1 -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,...Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following adverse reactions are described elsewhere in the labeling:
Early Death [see Warnings and Precautions (5.1) , Clinical Studies (14) ] Cytokine Release Syndrome [see Warnings and Precautions (5.2) ] Neurologic Toxicities [see Warnings and Precautions (5.3) ] Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] Infections [see Warnings and Precautions (5.6) ] Prolonged Cytopenias [see Warnings and Precautions (5.7) ] Hypogammaglobulinemia [see Warnings and Precautions (5.8) ] The most common nonlaboratory adverse reactions (incidence ≥20%) include pyrexia, CRS, hypogammaglobulinemia, infections–pathogen unspecified, musculoskeletal pain, fatigue, febrile neutropenia, hypotension, tachycardia, diarrhea, nausea, headache, chills, upper respiratory tract infection, encephalopathy, edema, dyspnea and viral infections. ( 6.1 ) The most common Grade 3 or 4 laboratory adverse reactions (incidence ≥50%) include leukocyte count decreased, neutrophil count decreased, lymphocyte count decreased, platelet count decreased, and hemoglobin decreased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety data described in the WARNINGS and PRECAUTIONS section reflect exposure to ABECMA in 349 patients with relapsed or refractory multiple myeloma: one randomized, open-label study with 222 patients in Study 1 and one single-arm, open-label study with 127 patients in Study 2. Study 1 The safety data described in this section reflect the exposure to ABECMA in Study 1, in which 222 patients with relapsed or refractory multiple myeloma received ABECMA across a dose range of 175 to 529 × 10 6 CAR-positive T cells (median dose: 445 × 10 6 CAR-positive T cells) [see Clinical Studies (14) ] . Patients with a history of CNS disease or requiring ongoing treatment with chronic immunosuppression were excluded. The median age of the safety population was 63 years (range: 30 to 81 years); 43% were 65 years or older, and 63% were men. The Eastern Cooperative Oncology Group (ECOG) performance status at baseline was 0 in 47%, 1 in 51%, 2 in 1.4% and 3 in 0.5% of patients. Four (1.8%) patients treated with ABECMA had creatinine clearance <45 mL/min. For details about the study population, [see Clinical Studies (14) ] . The most common (≥10%) Grade 3 or 4 nonlaboratory adverse reactions was febrile neutropenia (51%) and any infections (16%). The most common nonlaboratory adverse reactions (incidence ≥20%) included CRS, pyrexia, any infection, febrile neutropenia, hypogammaglobulinemia, musculoskeletal pain, hypotension, infections–pathogen unspecified, fatigue, tachycardia, diarrhea, nausea, headache, encephalopathy, dyspnea and edema. Serious adverse reactions occurred in 43% of patients. The most common nonlaboratory (≥5%) serious adverse reactions included infections–pathogen unspecified (10%), pneumonia (9%), viral infections (8%), encephalopathy (6%), pyrexia (6%) and sepsis (5%). Fatal adverse reactions occurred in 9%. Table 3 summarizes the adverse reactions that occurred in at least 10% of patients treated with ABECMA. Table 4 describes the most common Grade 3 or 4 laboratory abnormalities. Table 3: Adverse Reactions Observed in at Least 10% of Patients Treated in Study 1 CAR=chimeric antigen receptor. * Represents multiple related terms. a Coagulopathy includes activated partial thromboplastin time prolonged, blood fibrinogen decreased, coagulopathy, disseminated intravascular...Drug Interactions
7 DRUG INTERACTIONS Drug/Laboratory Test Interactions HIV and the lentivirus used to make ABECMA have limited, short spans of identical genetic material (RNA). Therefore, some commercial HIV nucleic acid tests may yield false-positive results in patients who have received ABECMA.
Contraindications
4 CONTRAINDICATIONS None. None. ( 4 )
Pregnancy and Breastfeeding
8.1 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.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING ABECMA is supplied in one or more infusion bag(s) (see below) containing a frozen suspension of genetically modified autologous T cells in 5% DMSO. Each infusion bag of ABECMA is overwrapped with a transparent plastic sleeve that is folded to the back of the infusion bag and individually packed in a metal cassette. ABECMA is stored in the vapor phase of liquid nitrogen and supplied in a liquid nitrogen dry vapor shipper. An RFI Certificate is affixed inside the shipper.
50 mL infusion bag and metal cassette (NDC 59572-515-01) 250 mL infusion bag and metal cassette (NDC 59572-515-02) 500 mL infusion bag and metal cassette (NDC 59572-515-03) Match the identity of the patient with the patient identifiers on the cassette(s) and infusion bag(s) upon receipt. Store ABECMA frozen in the vapor phase of liquid nitrogen (less than or equal to minus 130°C). Thaw ABECMA prior to infusion [see Dosage and Administration (2.2) ] .About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.