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?  

For these details, refer to the IMF publication Understanding Elrexfio as listed under Related Content below. 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.