idecabtagene vicleucel

Action and Spectrum

Actions and Spectrum: 

idecabtagene vicleucel (brand name: Abecma) is an innovative therapy used to treat multiple myeloma, a type of cancer affecting plasma cells in the bone marrow. It is classified as a chimeric antigen receptor (CAR) T-cell therapy and works by utilizing genetically modified immune cells to target and destroy cancer cells. Here’s some information on the action and spectrum of idecabtagene vicleucel: 

• Action: idecabtagene vicleucel involves a multi-step process to attack cancer cells. It starts with extracting a patient’s T cells, a white blood cell, from their bloodstream. These T cells are then modified in the laboratory to express a specific chimeric antigen receptor (CAR) on their surface. The CAR is designed to recognize and bind to a protein called B-cell maturation antigen (BCMA) on multiple myeloma cells’ surfaces. 
• Spectrum: idecabtagene vicleucel is indicated for treating adult patients with the relapsed/ multiple myeloma of refractory, which means the disease has returned or has not responded to previous treatments. It is specifically approved for patients who have received a minimum of four earlier lines of therapy, together with an immunomodulatory agent, proteasome inhibitor, anti-CD38 monoclonal antibody. 

The use of idecabtagene vicleucel is intended for patients with limited treatment options and provides a potential alternative for those who have exhausted other available therapies.

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Hypophosphatemia (45%) 

Upper respiratory tract infection (34%) 

Motor dysfunction (11%) 

Diarrhea (35%) 

Encephalopathy (26%) 

Dizziness (17%) 

Rash (14%) 

Hypogammaglobulinemia (41%) 

Weight decreased (13%) 

Cytokine release syndrome (85%) 

Xerosis (11%) 

General physical health deterioration (11%) 

Anemia (63%) 

Lymphopenia (92%) 

Decreased appetite (22%) 

Infections, unspecified pathogen (51%) 

Tachycardia (19%) 

Nausea (29%) 

Edema (25%) 

Insomnia (13%) 

Anxiety (12%) 

Hypertension (11%) 

Oral pain (12%) 

Thrombocytopenia (63%) 

Hypotension (17%) 

Viral infections (27%) 

Pneumonia (17%) 

Dyspnea (13%) 

Constipation (16%) 

Musculoskeletal pain (45%) 

Headache (23%) 

Febrile neutropenia (16%) 

Neutropenia (96%) 

Leukopenia (96%) 

Chills (11%) 

Vomiting (15%) 

1-10% 

Hypokalemia (<10%) 

Hypofibrinogenemia (<10%) 

Weight decreased (1.6%) 

Coagulopathy (9%) 

Gastrointestinal hemorrhage (3.1%) 

Hypocalcemia (<10%) 

Hyperglycemia (<10%) 

Renal failure (10%) 

Alkaline phosphatase increased (<10%) 

Hypertension (3.1%) 

Activated partial thromboplastin time increased (10%) 

Tremor (10%) 

Cardiomyopathy (1.6%) 

Hypoalbuminemia (<10%) 

Aphasia (7%) 

Pulmonary edema (2.4%) 

Hypoxia (2.4%) 

Fungal infections (8%) 

Atrial fibrillation (4.7%) 

Thrombosis (3.1%) 

Paresis (2.4%) 

Hypogammaglobulinemia (41%) 

Sepsis (9%) 

Dyspnea (2.4%) 

Encephalopathy (6%) 

Musculoskeletal pain (3.1%) 

AST increased (<10%) 

Ataxia (3.1%) 

Bacterial infections (3.9%) 

Viral infections (9%) 

Diarrhea (1.6%) 

Cytokine release syndrome (9%) 

Seizure (1.6%) 

Upper respiratory tract infection (1.6%) 

Hemophagocytic lymphohistiocytosis (3.1%) 

Delirium (6%) 

AST increased (<10%) 

Pneumonia (9%) 

Renal failure (2.4%) 

Fatigue (3.1%) 

Encephalopathy (26%) 

Hypertension (11%) 

Bilirubin increased (<10%) 

Pulmonary edema (2.4%) 

Hypoalbuminemia (<10%) 

Hypogammaglobulinemia (41%) 

Pyrexia (25%) 

Hypoxia (2.4%) 

Dyspnea (13%) 

Musculoskeletal pain (45%) 

General physical health deterioration (10%) 

<1% 

Decreased appetite (0.8%) 

Peripheral neuropathy (0.8%) 

Rash (0.8%) 

Hypogammaglobulinemia (0.8%) 

Dizziness (0.8%) 

Anxiety (0.8%) 

Black Box Warning

Black Box Warning: 

The black box warning for idecabtagene vicleucel includes information about the following potentially severe adverse reactions: 

• Cytokine Release Syndrome (CRS): idecabtagene vicleucel treatment can lead to CRS, a systemic response to the activation and proliferation of CAR T cells, releasing inflammatory cytokines. CRS can cause flu-like symptoms, high fever, hypotension, capillary leak syndrome, and organ dysfunction. Severe cases of CRS may require intensive care support and can be life-threatening. 
• Neurological Toxicities: idecabtagene vicleucel treatment can also cause neurological toxicities, including encephalopathy (altered mental status), delirium, seizures, aphasia, and other neurological events. These symptoms can be reversible or persist and can be severe or life-threatening. 
• Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS): HLH/MAS can occur with idecabtagene vicleucel treatment, leading to severe systemic inflammation. Symptoms may include fever, hepatosplenomegaly, cytopenias, and multi-organ dysfunction. Prompt identification and treatment are essential as HLH/MAS can be fatal. 
• Prolonged Cytopenia: idecabtagene vicleucel may cause prolonged cytopenia, including neutropenia, thrombocytopenia, and anemia, which may require transfusions or supportive care. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

The contraindications for idecabtagene vicleucel (Abecma) include: 

• Hypersensitivity: It is contraindicated in patients with a severe hypersensitivity reaction to idecabtagene vicleucel or any of its components. 
• Previous Severe Neurological Toxicity: It is contraindicated in patients who have experienced severe or life-threatening neurological toxicity with previous CAR T-cell therapy. 

Caution 

Specific cautions associated with the use of idecabtagene vicleucel (Abecma) include: 

• Cytokine Release Syndrome (CRS): idecabtagene vicleucel can cause CRS, an immune response associated with releasing inflammatory cytokines. CRS can manifest with symptoms such as fever, chills, hypotension, capillary leak syndrome, and organ dysfunction. Close monitoring for signs of CRS and appropriate management strategies, such as administering tocilizumab or corticosteroids, should be implemented. 
• Neurological Toxicities: Neurological toxicities, including encephalopathy, delirium, seizures, and other neurologic events, can occur following treatment with idecabtagene vicleucel. Patients should be closely monitored for neurological symptoms, and appropriate management measures should be taken if toxicities develop. 
• Infections: Patients treated with idecabtagene vicleucel are more likely to develop infections. Before treatment, any pre-existing infections should be appropriately managed. During and after treatment, patients should be monitored for signs and symptoms of infection, and appropriate anti-infective measures should be taken as necessary. 
• Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS): HLH/MAS, which is characterized by severe systemic inflammation, can occur as a complication of idecabtagene vicleucel treatment. Prompt identification and appropriate management of HLH/MAS symptoms, including fever, cytopenias, hepatosplenomegaly, and multi-organ dysfunction, are essential. 
• Prolonged Cytopenia: idecabtagene vicleucel treatment can lead to prolonged cytopenia, including neutropenia, thrombocytopenia, and anemia. Monitoring of blood counts should be performed regularly, and supportive care measures such as transfusions or growth factors may be required. 

Other precautions and warnings may exist, and it is crucial to consult the prescribing information, package inserts, or healthcare professionals for comprehensive and up-to-date information regarding the cautions specific to idecabtagene vicleucel. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: Not assigned 

Lactation:   

Excreted into human milk is Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

idecabtagene vicleucel is a novel immunotherapy that utilizes genetically modified T cells to target and eliminate multiple myeloma cells. Here is an overview of the pharmacology of idecabtagene vicleucel: 

idecabtagene vicleucel is classified as a chimeric antigen receptor (CAR) T-cell therapy. It involves the genetic modification of a patient’s T cells to express a CAR specific to the B-cell maturation antigen (BCMA), which is present on the surface of multiple myeloma cells. The CAR consists of an extracellular antigen recognition domain, a transmembrane domain, and intracellular signaling domains. Once the modified CAR T cells are infused back into the patient, they can recognize and bind to BCMA-expressing multiple myeloma cells, destroying them. 

Pharmacodynamics: 

Mechanism of action: idecabtagene vicleucel is a type of immunotherapy known as a chimeric antigen receptor (CAR) T-cell therapy. Its mechanism of action involves genetic modification of an individual’s T cells to target and eliminate multiple myeloma cells specifically. Here’s a breakdown of its mechanism of action: 

• Collection of T Cells: First, a patient’s T cells, a type of white blood cell (W.B.C) involved in the immune response, are collected through leukapheresis. These T cells are then sent to a manufacturing facility. 
• Genetic Modification: The collected T cells undergo genetic modification to introduce a CAR (chimeric antigen receptor) into their genome in the manufacturing facility. The CAR is engineered to recognize a specific antigen called B-cell maturation antigen (BCMA), which is present on multiple myeloma cells’ surfaces. 
• CAR Structure: The CAR consists of several components. It has an extracellular antigen recognition domain that binds to BCMA, a transmembrane domain that anchors the CAR to the T cell membrane, and intracellular signaling domains that activate the T cell when the CAR is engaged. 
• CAR T Cell Expansion: Once the T cells are genetically modified to express the CAR, they are expanded in the laboratory to increase their numbers. This process generates a large population of CAR T cells specific to BCMA. 
• Infusion and Targeting: The expanded population of CAR T cells is then infused back into the patient. The CAR T cells circulate in the bloodstream, and when they encounter multiple myeloma cells expressing BCMA, the CAR binds to BCMA on the surface of these cancer cells. 
• T Cell Activation and Killing: The CAR’s engagement with BCMA triggers a signaling cascade within the CAR T cell, leading to its activation. Activated CAR T cells release cytotoxic molecules and cytokines, initiating a targeted attack on the multiple myeloma cells. This can result in the destruction of cancer cells and a reduction in the tumor burden. 

Pharmacokinetics: 

Absorption 

idecabtagene vicleucel is administered intravenously, directly infusing it into the bloodstream. As a result, it is rapidly and completely absorbed into the systemic circulation. 

Distribution 

After infusion, idecabtagene vicleucel distributes throughout the body. It targets cancer cells expressing the B-cell maturation antigen (BCMA) on the surface, commonly found in multiple myeloma cells. The infused CAR T-cells circulate in the bloodstream and migrate to the tumor sites, where they recognize and bind to BCMA, initiating an immune response against the cancer cells. 

Metabolism 

As an immunotherapy, idecabtagene vicleucel does not undergo traditional metabolic processes in the body. However, the CAR T-cells themselves may undergo activation, proliferation, and interaction with other immune system components, ultimately leading to the elimination of cancer cells. 

Elimination and Excretion 

Similarly, there is no specific excretion process for idecabtagene vicleucel itself. Once the infused CAR T-cells have completed their immune response against the cancer cells, they may undergo apoptosis (cell death) or be cleared by the immune system. Any remnants of the CAR T-cells or their byproducts are likely eliminated from the body through normal physiological processes. 

Adminstartion

Administration: 

Intravenous administration 

idecabtagene vicleucel (Abecma) is administered as a one-time infusion. The administration process involves several steps and should be performed by healthcare professionals experienced in CAR T-cell therapy. Here is a general overview of the administration process: 

• Pre-infusion Evaluation: Before administering idecabtagene vicleucel, patients undergo a comprehensive evaluation that includes laboratory testing, imaging, and assessment of disease status. This evaluation helps determine the eligibility and suitability of the patient for CAR T-cell therapy. 
• Collection of T Cells: A process known as leukapheresis is performed to collect the patient’s T cells from their blood. The collected T cells are then sent to a manufacturing facility, and they are genetically modified to express a CAR (chimeric antigen receptor) specific to the B-cell maturation antigen (BCMA) found on multiple myeloma cells. 
• Manufacturing Process: In the manufacturing facility, the collected T cells undergo a process of genetic modification to introduce the CAR into their genome.  
• Preparatory Regimen: Before the infusion of idecabtagene vicleucel, patients may undergo a preparatory regimen that includes lymphodepleting chemotherapy. This chemotherapy helps create an environment that allows the infused CAR T cells to proliferate and exert their anti-cancer effects. 
• Infusion: Once the idecabtagene vicleucel product is prepared, it is administered to the patient by intravenous (IV) infusion. The infusion usually occurs in a healthcare facility, such as a hospital or specialized CAR T-cell therapy center. The infusion process typically takes about 30 minutes. 
• Post-infusion Monitoring and Supportive Care: Following the infusion, patients are monitored for any potential side effects or complications, such as cytokine release syndrome (CRS) or neurological toxicities. Monitoring may include vital signs, laboratory testing, and assessments of organ function. Supportive care measures, such as medications to manage CRS or neurological symptoms, may be initiated as needed. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: idecabtagene vicleucel 

Pronounced: [ EYE-de-KAB-ta-jeen-vik-LOO-sel ] 

Why do we use idecabtagene vicleucel? 

idecabtagene vicleucel (brand name: Abecma) is primarily used to treat a particular type of cancer called multiple myeloma. It is generally indicated for adult patients with the relapsed/ multiple myeloma of refractory, who received a minimum of four earlier lines of therapy, including an immunomodulatory agent (such as lenalidomide), a proteasome inhibitor (such as bortezomib), and anti-CD38 monoclonal antibody (such as daratumumab). 

idecabtagene vicleucel is a CAR (chimeric antigen receptor) T-cell therapy that involves modifying a patient’s T cells (another type of white blood cell) in the laboratory to express a CAR specific to the B-cell maturation antigen (BCMA) found on multiple myeloma cells. These modified CAR T cells are then infused back into the patient, they can recognize and target BCMA-expressing multiple myeloma cells, leading to their destruction. 

Using idecabtagene vicleucel provides a treatment option for adult patients with a relapsed/multiple myeloma of refractory,who have exhausted other available therapies. It offers a potential alternative for patients with limited treatment options who may have experienced disease progression despite previous treatments.