FDA Approval of a New Drug Elrexfio Offers More Option for Multiple Myeloma

Elrexfio is the fifth innovative multiple myeloma therapy and the third bispecific antibody treatment in the fight against multiple myeloma. The accelerated approval is to treat patients who have already progressed with multiple lines of cancer therapy including chemotherapy and targeted therapy.

 

Multiple Myeloma: The Basics

Multiple myeloma is an incurable type of blood cancer involving plasma cells. Plasma cells are the mature white blood cells in your bone marrow that fight against infection. These cancer cells can grow out of proportion and replace the healthy bone marrow cells. They can eventually spread to other parts of the body and cause symptoms.

Treatment of multiple myeloma involves a combination of a targeted drug, biological therapy, steroid, chemotherapy, and stem cell transplant. One question that has been the subject of ongoing research and debate is how to sequence these therapies to better kill myeloma cells, reduce rates of relapse, and improve quality of life.

Treatment options were limited in the past when the disease recurred despite trying all the available drugs on the market. Over the last few years, CAR T-cell therapy and bispecific antibody drugs have a game changers for patients with multiple myeloma. Bispecific antibodies work by helping your immune system to recognize and attack cancer, but they are not for everyone. If you’re diagnosed with multiple myeloma, it’s worth discussing this with your doctor.

 

Bispecific Antibodies: Combining the Benefits of Two Drugs in One

Bispecific antibodies are a type of immunotherapy that helps your immune system to fight your myeloma cancer cells.

These are proteins that can bind to two targets (bispecific):

• A protein called B-cell maturation antigen (BCMA) on the surface of myeloma cells
• The CD3 receptor located on the surface of T-cells (immune system cells)

BCMA is expressed heavily on multiple myeloma cells, making it a good target for Elrexfio. The drug brings the myeloma cells close to your immune system cells and activates the immune system in your body to kill the myeloma cells.

What Are Bispecific Antibodies?

Bispecific antibodies including CAR T-cell therapy are the newest class of medication approved for patients with relapsed/refractory multiple myeloma — and have been shown to be very effective. CAR T-cell therapy (ide-cel and cilta-cel) is often used as a fourth-line option after people have tried and failed to respond to three other treatments including a proteasome inhibitor (Velcade), an immunomodulatory agent (Revlimid), and an anti-CD38 monoclonal antibody (Darzalex).

CAR T-cell is a time-consuming process and may not be readily available to you. To solve this problem, “an off-the-shelf approach” has been investigated. “Off-the-shelf approach” is basically a type of ready-made CAR-T that is made from the cells of healthy volunteers. Bispecific antibodies are “an off-the-shelf approach to using the body’s immune system to treat cancer,” Dr. Schuster, medical oncologist at Penn Medicine, tells SurvivorNet. “That means there’s no need to collect a patient’s cells and do gene therapy on them to direct them against the cancer.”

One such treatment is BiTE (bispecific T-cell engager) antibodies that have been approved for multiple myeloma and are available as an off-the-shelf treatment. Thus far, BCMA is the most common target for myeloma BiTEs with the exception of the novel drug Talvey (generic name: talquetamab). Talvey uses GPRC5D, an antigen that is highly expressed in myeloma cancer cells.

Details of the Study

Elrexfio is currently the third BCMA-targeted drug on the market. Its FDA approval in August 2023 is based on the results from phase 1 and phase 2 clinical trials. Results from the phase 2 MagnetisMM-3 trial, published in the journal Nature Medicine in August 2023.

• A total of 123 previously treated patients have received at least four prior lines of therapy and their cancer has come back or did not respond to prior treatment.
• These patients did not receive any BCMA-directed therapy in the past.
• The primary goal of this trial was to look at ORR (objective response rate). This refers to the percentage of patients who see their disease shrink or disappear because of treatment.
• The study shows that 61% of study participants responded to treatment and 35% of patients had a complete response.
• Almost half of the patients in the trial had cytokine release syndrome. Fortunately, none of the patients experienced severe cytokine release syndrome.

In an interview with Pfizer Ajay Nooka, MD, of the Winship Cancer Institute of Emory University in Atlanta, stated: “By offering durable clinical response with an established safety profile and the convenience of subcutaneous administration, Elrexfio provides a much-needed new option for heavily pretreated multiple myeloma patients who are struggling with relapsed myeloma.”

How to Take Elrexfio

The first time you receive this medication, you will receive a once-a-week dosing as an under-the-skin (subcutaneous) injection. If you respond well to this medication and no side effects are noted for six months, there’s a possibility that your doctor may switch the drug to a two-weekly interval schedule.

Your doctor will give you “pre-medications” to prevent adverse reactions. These may include a combination of steroids, Benadryl, and Tylenol.

The Potential for Side Effects

Elrexfio is a bispecific antibody, which has potential side effects people should be aware of. There are a number of things you can do to manage these side effects. Talk to your doctor to help you decide what will work best for you.

Dr. Catherine Diefenbach, Director of the Clinical Lymphoma program at Perlmutter Cancer Center, previously told SurvivorNet that, “as a class, bispecific antibodies tend to have some of the same side effects as CAR T-cell therapy but at a much lower level.

“[They] all generally tend to occur in the first cycle of therapy, sometimes the beginning of the second cycle. Subsequently, there is very low toxicity with these therapies,” she added.

These are some of the most common side effects associated with Elrexfio:

Cytokine release syndrome
Neurologic toxicity
Infections
Drop in red and white blood cell counts
Elevated liver enzymes

Perhaps the biggest red flag is cytokine release syndrome (CRS). When your immune system cells begin to attack the myeloma cells, they release signaling proteins called “cytokines.” The release of cytokines triggers damaging inflammation leading to CRS. You may experience headaches, fever, rash, fast heartbeat, difficulty breathing, and low blood pressure.

In more serious cases, these medications can cause inflammation of the central nervous system, leading to neurological symptoms.

The good news is, for most people, the symptoms are mild. However, it’s important to let your physician know if you experience any side effects.

Questions to Ask Your Doctor

If you or a loved one has been diagnosed with relapsed/refractory multiple myeloma, please discuss the role of personalized treatment options with a myeloma specialist. Here are some questions you may want to consider asking:

What will treatment with Elrexfio cost?
How often do I need to take the medication?
How will I feel during treatment?
Is it possible that I will have lingering side effects?
What are the advantages and disadvantages of Elrexfio?

Learn more about SurvivorNet's rigorous medical review process.

---