ABECMA (idecabtagene vicleucel)

ABECMA® (idecabtagene vicleucel, also known as “ide-cel”) is the first-in-class B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell immunotherapy approved by the U.S. Food and Drug Administration (FDA) in March 2021 for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) after 4 or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.

In April 2024, the FDA approved Abecma for the treatment of RRMM after 2 or more prior lines of therapy. This approval is based on the data from the KarMMa-3 phase III clinical trial, which demonstrated a progression-free survival (PFS) of roughly 13 months in the Abecma arm of the study vs. 4 months in the control arm with standard regimens. 

Immunotherapy and Abecma 

The immune system is made up of a complex network of cells, tissues, organs, and the substances they make. The immune system involves multiple mechanisms that work together to protect and defend the human body from 

•  external threats (e.g., bacteria, viruses, toxins) 
•  internal threats such as cancer

The immune system helps to destroy infected and diseased cells and to remove cellular debris while protecting healthy cells. 

Myeloma interferes with the normal function of the body’s immune system.s. Designed to protect us from harm, the immune system is very complex.  To learn more about the immune system and myeloma, read the IMF’s publication Understanding the Immune System in Myeloma.

Immunotherapy is a treatment that enhances the body’s natural defenses to protect us from harm. Abecma is a type of immunotherapy, a personalized chimeric antigen receptor (CAR) T-cell therapy that is manufactured for each individual patient using the patient’s own T cells. It is delivered as a one-time infusion. 

T cells (T lymphocytes) are a type of white blood cell. T cells are an important part of our immune system by helping the body fight infection and disease. T cells can be distinguished from other white blood cells by the presence of a T-cell receptor (TCR) on the cell surface. T cells can recognize and bind to specific antigens, thereby triggering an immune response. 

T cells can recognize myeloma cells as foreign and cancerous. However, as myeloma grows, the number of T cells is significantly reduced. In turn, their function is blocked, thus allowing the myeloma to continue to grow. T cells are needed to recognize myeloma cells as foreign and can destroy them. 

Who Is a Candidate for Abecma? 

 In March 2021, the FDA approved Abecma for the treatment of adult patients with relapsed or refractory myeloma after four or more prior lines of therapy including 

• an immunomodulatory agent,  
• a proteasome inhibitor, and  
• an anti-CD38 monoclonal antibody.  

Abecma is the first CAR T-cell therapy for myeloma to be approved by the FDA, and it is the first to target BCMA. 

In April 2024, the FDA approved Abecma for the treatment of RRMM after 2 or more prior lines of therapy. This approval is based on data from the KarMMa-3 phase III clinical trial. This trial demonstrated a progression-free survival (PFS) of roughly 13 months in the Abecma arm of the study versus 4 months in the control arm with standard regimens. This new FDA approval expands the previous indication. Now, this important CAR  T-cell therapy is available to patients earlier in their treatment journey.

How Abecma Works 

CAR T-cell therapy with Abecma does the following: 

1. It takes the patient’s own T cells and engineers them to identify the B-cell maturation antigen (BCMA) receptor on the surface of myeloma cells. 
2. It then binds to this receptor. 
3. Finally, it destroys the myeloma cells. 

BCMA is a protein involved in myeloma cell growth and survival. BCMA is found on the surface of nearly all cells in patients with myeloma. It is on both myeloma cells and healthy cells. BCMA is also known as tumor necrosis factor receptor superfamily member 17 (TNFRSF17).

Collection  

The patient’s own T cells are collected by a procedure called apheresis, sometimes also called leukapheresis. Apheresis is a procedure whereby whole blood is taken from the patient. The blood is then passed through a machine that separates the blood into its individual components so that one particular component can be collected. Next, the remaining blood components are immediately re-infused back into the bloodstream of the patient.

This process is similar to how a patient’s own stem cells may be collected for an autologous transplant.  

Manufacturing  

The harvested T cells are sent to a highly specialized manufacturing laboratory where they are engineered to attack the myeloma. The laboratory inserts a gene into the patient’s T cells. This genetically modifies the T-cells to recognize and attach to BCMA. An Abecma BCMA T-cell product unique to the patient is created.  

The patient’s genetically engineered T cells are grown in the lab until millions of cells have multiplied. There must be enough active T cells for the therapy to be effective. The process usually takes approximately 4 weeks. 

Preparation  

Approximately 5 days before the CAR T cells are reinfused, the patient begins a 3-day, low-dose chemotherapy regimen to prepare the body to more easily receive the CAR T cells.  

Infusion  

Approximately 4 weeks after the initial T-cell collection, the Abecma BCMA T-cell product is administered to the patient by an infusion through an intravenous (IV) catheter. The Abecma dose can be administered in one or more infusion bags, with up to 30 minutes for each infusion bag. 

The infused CAR T cells immediately begin to seek out the myeloma cells in the body and attack them. As a precaution, due to the specialized nature of T-cell therapy and the possibility of side effects during this process, many patients are admitted to the hospital for about a week. Abecma must be administered at a certified treatment center. 

Activation  

Abecma recognizes and binds to BCMA on myeloma cells, leading to the destruction of BCMA-expressing myeloma cells. The CAR T cells become activated and begin to directly destroy the cell. They also engage other parts of the immune system to help.    

Monitoring 

Monitoring ensures that the Abecma treatment is working. It helps with identifying any potential side effects. For at least 7 days after receiving the infusion of Abecma, the patient is monitored daily at the certified healthcare facility where the treatment was administered. 

For at least 4 weeks after the infusion of Abecma, the patient should remain within 2 hours travel to the certified healthcare facility where the treatment was administered. This is the approximate timeline of treatment with Abecma. Yet, every patient is different and the total time it takes to complete the process may vary.

Effects on Your Ability to Drive and Operate Machinery When Undergoing Abecma Therapy 

For at least 8 weeks following the Abecma infusion, you may be at risk for the following: 

• temporary memory and coordination problems 
• sleepiness 
• confusion 
• dizziness 
• seizures 

Don’t drive, operate heavy machinery, or engage in any activities that could be dangerous or hazardous if you are not mentally alert. Be sure to discuss with your healthcare team any potential issues that you may be experiencing.  

Important Safety Information About Abecma

Abecma may cause side effects that are severe or life-threatening. Immediately contact your doctor or get emergency help if you experience any of the following: 

• difficulty breathing 
• fever of 100.4°F/38°C or higher 
• chills or shivering 
• confusion 
• dizziness or lightheadedness 
• shaking or twitching (tremors) 
• fast or irregular heartbeat 
• severe fatigue 
• severe nausea 
• vomiting 
• diarrhea  

Do not donate blood, organs, tissues, or cells for transplantation.

HIV tests and Abecma Use 

Treatment with Abecma may cause a false-positive human immunodeficiency virus (HIV) test result by some commercial tests. Patients treated with Abecma may develop secondary malignancies and should be monitored lifelong.  

Possible Common Side Effects of Abecma  

Tell your doctor immediately if you develop any of these or other symptoms after receiving Abecma.

The side effects that occurred in 20% or more patients in the clinical trial include the following: 

• cytokine release syndrome (CRS) 
• infections 
• fatigue 
• musculoskeletal pain 
• hypogammaglobulinemia 
• diarrhea 
• upper respiratory tract infection 
• nausea 
• viral infections 
• encephalopathy (disease in which the functioning of the brain is affected) 
• edema 
• fever 
• cough 
• headache 
• decreased appetite 

The above listed side effects are the most common of the possible side effects of Abecma. 

Patients on Abecma may also experience Cytokine Release Syndrome. 

Cytokine Release Syndrome and Abecma

Cytokines are proteins that circulate in the bloodstream, usually in response to infection. Cytokines can stimulate or inhibit the growth or activity in other cells. 

Cytokine release syndrome (CRS) is a potentially fatal, uncontrolled immune reaction in which cytokines become highly elevated and trigger an overwhelming immune system response. A cytokine “storm” can seriously damage body tissues and organs. The CRS toxicity results from the active destruction of the myeloma cells by the BCMA-targeted T cells. 

Symptoms of CRS, which can be severe or fatal, may include:

• fever
• difficulty breathing
• dizziness or lightheadedness 
• nausea  
• headache 
• fast heartbeat
• low blood pressure
• fatigue 

Immediately tell your doctor if you develop any of these symptoms or experience any other potential side effects of Abecma.   

In patients treated with Abecma in the KarMMa clinical trial, CRS of any grade occurred in 85% of patients using the Lee grading system. The median time to onset of CRS was 1 day after the infusion, and the median duration of CRS was 7 days.   

Other Side Effects  

Abecma can lower one or more types of your blood cells, which may make you feel weak or tired, or increase your risk of severe infection or bleeding. Abecma can increase the risk of life-threatening infections that may lead to death. Tell your doctor immediately if you develop a fever, are feeling tired, or have bruising or bleeding.  

Clinical Trials and Abecma 

A clinical trial is a medical research study with people who volunteer to test scientific approaches to a new treatment or a new combination therapy. Each clinical trial is designed to find better ways to prevent, detect, diagnose, or treat cancer and to answer scientific questions. 

Numerous clinical trials with Abecma are ongoing. Some clinical trials are enrolling patients. Contact the IMF InfoLine or visit clinicaltrials.gov for up-to-date information. 

Access to Abecma  

Abecma is administered only at certified treatment centers. More information is available at Abecma.com or call 1.888.805.4555. Abecma is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Please visit AbecmaREMS.com or call 1.888.423.5436.