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) for use in myeloma. It is the first CAR T-cell therapy to be approved by the FDA for patients with myeloma and the first CAR T-cell therapy approved by the FDA that targets BCMA. 

Immunotherapy and Abecma 

Myeloma interferes with the normal function of the body’s immune system. Immunotherapy, which is sometimes called “biological therapy,” is treatment that enhances the body’s natural defenses. Designed to protect us from harm, the immune system is very complex. T cells (T lymphocytes) are one of the most important parts of our immune system. T cells recognize myeloma cells as foreign and cancerous. However, as myeloma grows, the number of these key T cells is significantly reduced, and their function blocked. As a result, myeloma can continue to grow. T cells are needed to recognize myeloma cells as foreign so that they can destroy those myeloma cells.  

CAR T-cell Therapy with Abecma 

CAR T-cell therapy with Abecma takes the patient’s own T cells and engineers them to attack and destroy the myeloma. The T cells are engineered to identify the BCMA antigen or receptor found on the surface of myeloma cells, bind to this antigen, and destroy the myeloma cells. (BCMA is found on healthy cells as well.) To achieve this goal, the T cells are “harvested” from the bloodstream. Then, they are sent to a highly specialized manufacturing laboratory to be engineered to attack the myeloma. This process involves both the engineering and the growing of enough active T cells for the therapy to be effective. It takes approximately 4 weeks. Then the Abecma BCMA T-cell product is administered to the patient by way of an infusion. The infused T cells immediately begin attacking the myeloma. 

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.  

In May 2021, Abecma was approved in Canada for adult patients with myeloma who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody and who are refractory to their last line of treatment.  

In August 2021, the European Commission approved Abecma for patients with relapsed and refractory myeloma who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression while still receiving their last treatment regimen. It was granted conditional approval for one year. This approval can be converted to full marketing authorization once additional data is submitted and assessed.  

What Are Some Multiple Myeloma Clinical Trials with Abecma? 

The phase II KarMMa trial 

The FDA approval of Abecma was based on the results of the phase II  KarMMa clinical trial. Patients were treated with their own T cells, which were engineered to target BCMA. In this study, 128 patients received treatment. Rapid, deep, and durable responses were achieved by 72% of patients. Minimal residual disease (MRD)-negative status was achieved in 33 (26%) of treated patients. The safety profile of Abecma is generally predictable, including cytokine release syndrome (CRS) and neurologic toxicities that are mostly low-grade with early onset and resolution. The CRS toxicity is a result of the active destruction of the myeloma cells by the BCMA-targeted T cells.

Dr. Nikhil C. Munshi, the principal investigator of the KarMMa clinical trial, summarizes the importance of Abecma as follows: “In the phase II KarMMa clinical trial, ide-cel elicited rapid responses in the majority of patients, and these deep and durable responses were observed in patients with triple-class exposed and refractory multiple myeloma. As a treating physician, I often work with patients with relapsed or refractory myeloma who are in critical need of new therapies. Now, with the FDA approval of Abecma, we are excited to finally be able to offer patients a new, effective personalized treatment option that is delivered through a single infusion.” 

The results of the KarMMa clinical trial were extremely promising, with a median response duration of 10.9 months, median progression-free survival (PFS) of 8.6 months, and median overall survival (OS) of 24.8 months. Patients who achieved a complete response (CR) or better had a longer response duration of 19 months. The patients participating in the study had a one-time infusion of CAR T cells and had no treatment after the infusion was done, therefore allowing for a longer time off myeloma therapy.  

The response rates demonstrated in the phase II KarMMa clinical trial of Abecma in relapsed and refractory myeloma offer an opportunity for patients with heavily pretreated disease to have deep and durable responses. Furthermore, a one-time infusion approach allows patients more time without ongoing therapy. Numerous additional clinical trials with Abecma are ongoing or planned.  

How Abecma Works 

Abecma is a personalized immune cell therapy delivered as a one-time infusion, manufactured for each individual patient using the patient’s own T cells. In brief, the process of CAR T-cell therapy is about collecting a patient’s T cells, training them to attack myeloma cells, multiplying those T cells in the lab, and then finally giving them back to the patient.  

Collection  

Much like collecting stem cells for an autologous transplant, the patient’s own T cells are collected by a procedure called apheresis or leukapheresis. 

Manufacturing  

The manufacturing process inserts into the collected T cells a gene that makes the cells express a chimeric antigen receptor (CAR) on the cell surface. CARs are "hooks” added to your T cells to create Abecma that is unique to you. This is how the patient’s harvested T cells are genetically modified to recognize and attach to BCMA, a protein that is nearly universally expressed on myeloma cells. The patient’s T cells are multiplied in the lab to manufacture millions of cells. This 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 into prepare the body to more easily receive the CAR T cells.  

Infusion  

Due to the specialized nature of T-cell therapy, Abecma must be administered at a certified treatment center. Approximately 4 weeks after the initial T-cell collection, the CAR T cells are infused into the patient 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 CAR T cells will now seek out the myeloma cells in the body and attach to them. As a precaution, in case possible side effects occur during this process, most patients are admitted to the hospital for about a week.  

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 

For at least 7 days after the infusion, the patient is monitored daily at the certified healthcare facility where treatment was administered. Patients must remain within 2 hours of the certified healthcare facility where treatment was administered for at least 4 weeks after being treated with Abecma. This is so their doctor can check that the Abecma treatment is working and to help with any potential side effects. 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 

These are the most common of the possible side effects of Abecma:

  • cytokine release syndrome (CRS) and it symptoms, which can be severe or fatal, may include the following: 
  • 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 if you 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.  

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.  


 


The International Myeloma Foundation medical and editorial content team

Comprised of leading medical researchers, hematologists, oncologists, oncology-certified nurses, medical editors, and medical journalists, our team has extensive knowledge of the multiple myeloma treatment and care landscape. Additionally, Dr. Brian G.M. Durie reviews and approves all medical content on this website. 

Last Medical Content Review: May 7, 2024

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