ELREXFIO (elranatamab-bcmm)

What Is Elrexfio?  

ELREXFIO® (also known as elranatamab-bcmm, the generic drug name) is a B-cell maturation antigen (BCMA)-CD3-directed bispecific antibody immunotherapy. In August 2023, the U.S. FDA granted accelerated approval of Elrexfio for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. 

How Does Elrexfio Work?  

Elrexfio binds to a B-cell maturation antigen (BCMA) on myeloma cells and CD3 on T-cells. By doing so, it brings these cells together and stimulates the T-cells to eliminate the myeloma cells effectively. 

How Does Elrexfio Differ from CAR T-cell Therapy?  

Elrexfio differs from CAR T-cell therapy in that there is no need to collect the patient’s T cells. Instead, Elrexfio engages the patient’s T cells directly after injection. Not having to collect, engineer, and manufacture T cells over several weeks shortens the time-to-treatment for the myeloma patient.  

When Should Elrexfio Be Used as a Treatment?  

Elrexfio is FDA-approved for patients with relapsed or refractory myeloma who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.  

How Has Elrexfio Been Used in Clinical Trials?  

MagnetisMM-3 Trial  

In August 2023, the journal Nature Medicine published a manuscript with the clinical trial results from the phase II MagnetisMM-3 study (NCT04649359). Heavily pretreated patients with relapsed or refractory myeloma, a high number of whom had poor prognostic features at baseline, were treated with Elrexfio. Elrexfio was shown to induce deep and durable responses with a manageable safety profile.  

• These patients received subcutaneous (SQ) injections at a dose of 76 mg once-weekly after a step-up priming dose regimen of 12 mg followed by 32 mg during the first week of treatment.  
• After 6 cycles, persistent responders were switched to biweekly dosing (every 2 weeks).  
• Patients in cohort A, who had not received prior BCMA-directed therapy, experienced the following:
  • They had an overall response rate (ORR) of 61%.  
  • A complete response (CR) was achieved by 35% or more of patients. 
  • 50 patients were switched to biweekly dosing.  
  • Also, 40 patients improved or maintained their response for at least 6 months.  
• With extended median follow-up of 17.6 months, which was presented at the annual meeting of the American Society of Hematology (ASH) in December 2023, median progression-free survival (PFS) was 17.2 months. 
• Median duration of response (DoR) had not been reached:
  • An 18-month rate of DoR was 68.8%.
  • The duration of CR was 89.1%.  

The results reported from the phase II study are consistent with results reported from the MagnetisMM-1 phase I study. 

How Will Elrexfio Be Made Available to Patients? 

Because of its unique toxicities, Elrexfio will be made available to patients through a special Risk Evaluation and Mitigation Strategy (REMS) program. A REMS program is “a drug safety program that the U.S. Food and Drug Administration (FDA) can require for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks.”   

How Should Elrexfio Be Administered, Dosed, and Scheduled? 

Elrexfio is intended for subcutaneous (SQ) injections by a healthcare provider only. The Elrexfio dosing schedule begins with 2 step-up doses in Week 1. Approximately 1 hour prior to receiving Elrexfio, patients are premedicated for both step-up doses on Days 1 and 4, as well as for the first treatment dose on Day 8. Premedication includes the following:

• acetaminophen (or comparable) 650 mg by mouth,
• dexamethasone (or comparable) 20 mg by mouth or by intravenous (IV) infusion, and
• diphenhydramine (or comparable) 25 mg by mouth.

Elrexfio Dosing Schedule

Dosing Schedule	Day	Elrexfio Dose	Elrexfio Dose
Step-Up Dosing Schedule	Day 1	Step-up dose 1	12 mg
Step-Up Dosing Schedule	Day 4	Step-up dose 2	32 mg
Step-Up Dosing Schedule	Day 8	First treatment dose	76 mg
Weekly Dosing Schedule	One week after first treatment dose and weekly thereafter	Subsequent treatement dose	76 mg

*Patients are premedicated for step-up doses on Days 1 and 4, as well as for the first treatment dose on Day 8.

Elrexfio is administered at the dose of 76 mg once weekly for 24 weeks. Then, it is given once every 2 weeks at the same dose in patients who respond to treatment. Elrexfio is continued at 76 mg until disease progression or unacceptable toxicity.

Due to the risk of a potential side effect called cytokine release syndrome (CRS), patients may be hospitalized for 48 hours after administration of the first step-up dose of Elrexfio on Day 1, and for 24 hours after administration of the second step-up dose of Elrexfio on Day 4.

Alternatively, your doctor may decide to treat you on an outpatient basis.

What Warnings and Precautions Should Patients Who Undergo Elrexfio Therapy Be Aware Of?  

The FDA requires a Risk Evaluation and Mitigation Strategy (REMS) program if a specific treatment has serious safety concerns. REMS programs support the use of such treatments and help ensure that the potential benefits outweigh the risks. Elrexfio is available only through a REMS program.

If you are treated with Elrexfio, you will receive a Patient Wallet Card that explains when to seek immediate medical attention, as well as the signs and symptoms of cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS). Share this card with your healthcare providers, and inform them about your Elrexfio treatment and when to contact your myeloma doctor.

For details about side effects of Elrexfio, visit the IMF publication Understanding Elrexfio. The IMF also encourages patients to learn about potential Elrexfio side effects and complications on the manufacturer’s website here.  The medication label provides full details. 

Cytokine release syndrome (CRS) 

Cytokines are proteins secreted by cells which can stimulate or inhibit the growth or activity in other cells. In patients with myeloma, cytokines are produced in the bone marrow and circulate in the bloodstream. Cytokines are normally released in response to hematologic-related events (low blood counts) and infection. 

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. CRS is the most frequent side effect observed with T-cell therapies, but the incidence and severity of CRS are lower with bispecific antibodies than with CAR T-cell therapy. 

Prevention and treatment of CRS 

To reduce the risk of CRS, patients receive pretreatment medications. In addition, therapy with Elrexfio is started with the step-up dosing schedule. Patients are monitored following the administration of Elrexfio. At the first sign of CRS, immediate evaluation must be made to consider the patient for hospitalization. Supportive care is administered based on severity of CRS. Further management should follow current practice guidelines. Elrexfio administration may be interrupted or discontinued, depending on severity of CRS. 

Neurologic toxicities 

Immune effector cell-associated neurotoxicity syndrome (ICANS) has occurred in patients following treatment with Elrexfio. ICANS often correlates with CRS, but it can also occur in the absence of CRS. After treatment with Elrexfio, ICANS can occur before, during, or after CRS onset, or after CRS resolution. ICANS may be severe, life-threatening, or fatal. Symptoms of neurologic side effects include but are not limited to confusion, disorientation, loss of consciousness, seizures, tremor, slower movements, changes in personality, depression, tingling and numbness of hands and feet, leg and arm weakness, facial numbness, and difficulty speaking, reading, or writing. 

Prevention and treatment of neurologic toxicities 

Patients must be monitored for signs and symptoms of neurologic toxicity during treatment with Elrexfio. At the first sign of neurologic toxicity, including ICANS, patients are provided supportive therapy based on severity, and Elrexfio treatment may also be withheld.

Patients are advised to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of Elrexfio. step-up dosing schedule and in the event of new onset of any neurologic toxicity symptoms until neurologic toxicity resolves.

Infections

Elrexfio can cause severe, life-threatening, or fatal infections. Do not start treatment with Elrexfio if you have an active infection.

Prevention and treatment of infections

You must be monitored for signs and symptoms of infection prior to and during treatment with Elrexfio. It is essential that you promptly report any infection to your doctor. Anti-infectives (e.g., antibiotics, antivirals) may be instituted, and Elrexfio may be withheld or discontinued based on severity. Your immunoglobulin (Ig) levels should also be monitored to assess if you may need intravenous immunoglobulin (IVIG).

Neutropenia

Elrexfio can cause neutropenia and febrile neutropenia. Neutropenia is a reduced level of neutrophils, a type of white blood cell necessary to combat bacterial infection. Having too few neutrophils can lead to infection. Febrile neutropenia is the development of fever, often with signs of infection, in a patient with neutropenia. Febrile neutropenia is usually treated with antibiotics even if an infectious source can’t be identified.

Prevention and treatment of neutropenia

Complete blood counts (CBC) should be measured at baseline and monitored periodically during treatment. Fever is the most common sign of neutropenia. If you have a fever, you must get immediate medical attention

Hepatotoxicity (liver damage)

Elrexfio may elevate liver enzyme aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin. Liver enzyme elevation can occur with or without concurrent CRS.

Prevention and treatment of hepatotoxicity

Your doctor will measure your liver enzymes and bilirubin at baseline and monitor during treatment as clinically indicated. Elrexfio may be withheld or discontinued if necessary.

Embryo-fetal toxicity

Exposure of an embryo or a fetus to a toxic substance may cause fetal harm.

Prevention and treatment of embryo-fetal toxicity

Females of reproductive potential and males with female partners of reproductive potential should use effective contraception during treatment with Elrexfio. Ask your doctor if it is also necessary to use effective contraception before treatment begins and after the last dose of treatment is administered.

Other potential side effects of Elrexfio

Other common side effects that occurred during treatment with Elrexfio in the MagnetisMM-3 clinical trial, having been absent before treatment, or side effects that worsened relative to the pretreatment state that were reported in the study were fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and fever.

In the MagnetisMM-3 clinical trial, the most common Grade 3 to 4 laboratory abnormalities that occurred in 30% or more of study patients were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets.
 

Access and Support for Elrexfio

Pfizer Oncology Together can help patients who have been prescribed Elrexfio and their care partners find financial assistance resources, regardless of insurance coverage, as well as receive one-on-one support from a Patient Access Navigator. Visit pfizeroncologytogether.com or call 1.877.744.5671.