Elrexfio (elranatamab-bcmm) for multiple myeloma
Fact-checked by What is Elrexfio for multiple myeloma?
Elrexfio (elranatamab-bcmm) is an antibody-based therapy approved for certain adults with multiple myeloma that has returned after treatment (relapsed) or proven non-responsive to treatment (refractory). Its approval in the U.S. and other countries is provisional, meaning that additional data confirming its therapeutic benefits will be needed to support its continued approval.
In multiple myeloma, plasma cells, which normally help the body fight infections, become cancerous and start growing out of control. T-cells, a type of immune cell, can kill these cancerous plasma cells (myeloma cells), but sometimes fail to recognize and destroy them.
Elrexfio is designed to help T-cells recognize and destroy myeloma cells. It is a bispecific antibody that recognizes and binds to two proteins. One is the CD3 protein on T-cells, and the other is the B-cell maturation antigen (BCMA) protein on plasma cells. By binding to both proteins simultaneously, Elrexfio activates T-cells and brings them into close proximity to the myeloma cells they are meant to destroy.
Pfizer developed Elrexfio, which is administered via under-the-skin (subcutaneous) injections. The company is sponsoring additional clinical trials that could support the medication’s full approval in the future.
Therapy snapshot
| Brand name | Elrexfio |
| Chemical name | Elranatamab-bcmm |
| Usage | Used to treat certain adults with relapsed or refractory multiple myeloma |
| Administration | Subcutaneous injection |
Who can take Elrexfio?
In the U.S., the Elrexfio’s accelerated approval covers adults with relapsed or refractory myeloma (RRMM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody.
The therapy has received similar conditional approvals in Europe and Canada.
Elrexfio’s U.S. prescribing information lists no contraindications to its use. However, it comes with a boxed warning for severe inflammatory responses and neurological complications that can be serious and life-threatening. For this reason, Elrexfio is only available in the U.S. through a restricted program called Elrexfio Risk Evaluation and Mitigation Strategy (REMS).
How is Elrexfio administered?
Healthcare providers administer Elrexfio as a subcutaneous injection, usually given into the abdomen or thigh. Dosing occurs in three to four phases:
- Step-up dosing: Patients begin treatment with three increasing doses over eight days. After the first dose, patients should stay in the hospital for 48 hours for monitoring, then for another 24 hours after the second dose. The third injection is typically the full recommended dose of 76 mg.
- Weekly dosing: After step-up dosing, patients generally receive the full recommended dose of 76 mg once weekly for 24 weeks, or about six months.
- Every-other-week dosing: If cancer responds at least partially to the weekly dosing schedule and the response is maintained for at least two months, patients may transition to a regimen with the same dose given every two weeks.
- Every-four-week dosing: If the response is still sustained with every-other-week dosing after another six months, patients may transition to a regimen with the same 76 mg dose given every four weeks.
Treatment should continue until the disease progresses or there is unacceptable toxicity.
About one hour before each of the first three doses — the two step-up doses and the first full 76 mg dose — patients should receive different premedications to help reduce the risk of side effects.
Elrexfio in clinical trials
Elrexfio’s accelerated approval in the U.S. was supported by data from the Phase 2 MagnetisMM-3 clinical trial (NCT04649359), which included RRMM patients who had received at least three prior lines of therapy.
The safety and efficacy of Elrexfio were assessed across several patient groups within the study:
- The trial’s efficacy population comprised 97 patients who had received at least four prior therapies, but no BCMA-directed therapies. In these patients, 58% had at least a partial response to treatment.
- Analyses of all 123 patients who didn’t receive BCMA-targeting therapies, regardless of prior lines of treatment, showed that 61% responded at least partially to treatment.
- In a subset of 63 patients who had received at least four prior therapies and a BCMA-directed therapy, the overall response rate was 33%, indicating that about a third achieved at least a partial response.
Full approval is pending on data from a confirmatory Phase 3 trial called MagnetisMM-5 (NCT05020236), which is enrolling adults with RRMM who have previously received at least one line of therapy, including a proteasome inhibitor and Revlimid (lenalidomide). The trial includes three parts:
- The first part will focus on assessing the safety and efficacy of various doses of Elrexfio when combined with Darzalex Faspro (daratumumab and hyaluronidase-fihj), another approved therapy for multiple myeloma.
- Part two will focus on comparing the effects of treatment across three groups: one in which patients will receive Elrexfio alone; another in which they will receive Elrexfio in combination with Darzalex Faspro; and the third in which they will receive a standard treatment combination of Darzalex Faspro, Pomalyst (pomalidomide), and the corticosteroid dexamethasone.
- In the third part, investigators will also test additional anti-infection measures in patients treated with either Elrexfio alone or together with Darzalex Faspro.
Results from the first part showed Elrexfio had a manageable safety profile and led to promising early responses.
Other ongoing trials in the MagnetisMM program are testing different treatment combinations across multiple myeloma populations.
Elrexfio side effects
The most commonly reported side effects with Elrexfio include:
- cytokine release syndrome
- fatigue
- injection site reactions
- diarrhea
- upper respiratory tract infection
- musculoskeletal pain
- pneumonia
- reduced appetite
- rash
- cough
- nausea
- fever
- low blood cell counts
Elrexfio carries a boxed warning noting that it may lead to potentially fatal cytokine release syndrome (CRS) — a sudden, heightened inflammatory response that affects the whole body. Step-up dosing, premedication, and careful monitoring can help reduce the risks associated with CRS. Depending on the severity of the reaction, doctors may recommend pausing Elrexfio until CRS resolves or permanently discontinuing treatment.
The therapy’s boxed warning also notes the increased risk for serious or life-threatening neurologic complications, including immune effector cell-associated neurotoxicity syndrome (ICANS). If symptoms emerge during treatment, treatment with Elrexfio may have to be paused or stopped.
Other potentially serious side effects of Elrexfio include:
- severe, life-threatening, or fatal infections
- abnormally low counts of a type of immune cell called neutrophils (neutropenia), which can increase infection risk
- liver toxicity
Patients will be monitored for these potential side effects during treatment; if they occur, treatment may need to be interrupted or permanently discontinued.
Elrexfio may be harmful to a developing fetus when administered to pregnant women. It’s recommended that females of reproductive potential use an effective method of contraception while taking Elrexfio and for four months after the last dose. It’s also recommended that women abstain from breastfeeding during treatment and for four months after discontinuing treatment.
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