Idecabtagene Vicleucel Ide-cel for the Treatment of Adult Patients with Relapsed or Refractory Multiple Myeloma

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 

Mechanism of Action 
ABECMA is a chimeric antigen receptor (CAR)-positive T cell therapy targeting B-cell maturation antigen (BCMA), which is expressed on the surface of normal and malignant plasma cells. The CAR construct includes an anti-BCMA scFv-targeting domain for antigen specificity, a transmembrane domain, a CD3-zeta T cell activation domain, and a 4-1BB costimulatory domain. Antigen-specific activation of ABECMA results in CAR-positive T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells. 

Pharmacodynamics 
Following ABECMA infusion, pharmacodynamic responses of CAR activation and anti-tumor efficacy were evaluated. Peak elevation of plasma cytokines, chemokines, and soluble immune mediators occurred within 14 days of ABECMA infusion and returned to baseline levels within one month. Rapid decreases in tumor markers associated with clinical response, including serum levels of soluble BCMA, and bone marrow CD138+ cells, as well as minimal residual disease (MRD) negative responses, were observed within the first month following ABECMA infusion. 

Pharmacokinetics
 Following ABECMA infusion, the CAR-positive cells proliferate and undergo rapid multi-log expansion followed by a bi-exponential decline. The median time of maximal expansion in peripheral blood (Tmax) occurred 11 days after infusion. ABECMA can persist in peripheral blood for up to 1 year post-infusion

INDICATIONS AND USAGE

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 four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody 

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 H1-antihistamine 
• Avoid prophylactic use of dexamethasone or other systemic corticosteroids.
•ABECMA is a cell suspension for intravenous infusion. 
• A single dose of ABECMA contains a cell suspension of 300 to 460 x 106 CAR-positive T cells in one or more infusion bags

WARNINGS AND PRECAUTIONS
• Hypersensitivity Reactions: Monitor for hypersensitivity reactions during infusion
• Infections: Monitor patients for signs and symptoms of an infection; treat appropriately 
• Prolonged Cytopenias: Patients may exhibit prolonged Grade 3 or higher cytopenias following ABECMA infusion. Monitor blood counts prior to and after ABECMA infusion 
• Hypogammaglobulinemia: Monitor and consider immunoglobulin replacement therapy
• Secondary Malignancies: In the event that a secondary malignancy occurs after treatment with ABECMA, contact Bristol-Myers Squibb at 1-888-805-4555
 • Effects on Ability to Drive and Use Machines: Advise patients to refrain from driving or operating heavy or potentially dangerous machines for at least 8 weeks after ABECMA administration 
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WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, AND PROLONGED CYTOPENIA 

• 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 lifethreatening CRS with tocilizumab or tocilizumab and corticosteroids. 

• 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, 5.2). • 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 (5.3). • Prolonged Cytopenia with bleeding and infection, including fatal outcomes following stem cell transplantation for hematopoietic recovery, occurred following treatment with ABECMA (5.7). • ABECMA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ABECMA REMS 

For more info visit https://www.fda.gov/media/147055/download

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