Understanding ELREXFIO™
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What you will learn from this booklet
Myeloma is a cancer that is not known to most patients at the time of diagnosis. If you have myeloma, it is important and helpful for you to learn about your disease, its treatment options, and supportive care measures in order to play an active role in your own medical care and to make good decisions about your care in partnership with your doctor.
If you are a patient with myeloma, we suggest that you read the IMF’s publication, Patient Handbook for Multiple Myeloma, which will help you to better understand this disease. In addition, this booklet will direct you to resources that may be relevant in your particular case. All IMF publications are free-of-charge and can be read, downloaded, or requested in printed format at publications.myeloma.org.
The IMF’s Understanding-series publications address specific drugs, drug classes, and combination therapies used to treat myeloma. These booklets also discuss supportive care measures that may help manage the symptoms and side effects of myeloma and its treatments. The IMF’s publication, Understanding Your Test Results, explains how myeloma is diagnosed, monitored, and assessed throughout the disease course.
Words in bold+blue type are explained in the IMF’s companion publication, Understanding Myeloma Vocabulary, a comprehensive glossary that also can be helpful in discussions with your doctor. Myeloma is complicated, but the language that describes it doesn’t have to be hard to understand.
If you are reading this booklet in electronic format, the light blue links will take you to the corresponding resources.
This booklet discusses Elrexfio™ (also known as elranatamab-bcmm, its generic drug name). Elrexfio was granted accelerated approval by the U.S. Food and Drug Administration (FDA) for the treatment of myeloma in August 2023.
Indications for treatment with Elrexfio
Elrexfio is approved by the FDA for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent , and an anti-CD38 monoclonal antibody, and their myeloma has come back or did not respond to prior treatment. This indication has received accelerated approval by the FDA based on clinical trial response rate and duration of response (DoR).
How Elrexfio works
Elrexfio is an immunotherapy that employs a patient’s own immune system to attack their myeloma cells. Elrexfio is a bispecific antibody, an artificial antibody that binds to two (“bi”) targeted cells. The term “bispecific” means that the drug has 2 “arms,” with one arm attaching to the myeloma cell through the BCMA tumor-specific antigen on the cell surface and the other arm attaching to and activating a local T cell (T lymphocyte) by its CD3 antigen.
T cells are a type of white blood cell (WBC) that play a central role in the immune system. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on the cell surface. The CD3 protein complex is involved in activating the T cell to release cytotoxic granules that kill the myeloma cell. Elrexfio bridges the myeloma cell and the T cell, bringing them together so that the T cell can be activated to engage the myeloma cell and destroy it.
A similar strategy is already used in myeloma, known as chimeric antigen receptor (CAR) T-cell therapy, for which T cells are collected from a patient
Figure 1. Elrexfio mechanism of action
and then altered in a laboratory to express a receptor on their surface that can attach to BCMA on the surface of a myeloma cell. These engineered cells are multiplied in a laboratory and then reinfused into the patient to attack their myeloma cells.
The difference with Elrexfio is that there is no need to collect the patient’s T cells, which are instead engaged directly by infusing the Elrexfio into the patient. Not having to collect, engineer, and manufacture T cells over the course of several weeks shortens the time to treatment for the myeloma patient. This facilitates easier access to treatment as bispecific antibodies are given “off-the-shelf.”
Clinical trial experience with Elrexfio
A clinical trial is a medical research study with people who volunteer to test scientific approaches to a new treatment or a new combination therapy. Each clinical trial is designed to find better ways to prevent, detect, diagnose, or treat cancer and to answer scientific questions.
In August 2023, the journal Nature Medicine published a manuscript with the clinical trial results from the phase II MagnetisMM-3 study. Elrexfio was shown to induce deep and durable responses with a manageable safety profile.
Heavily pretreated patients with relapsed or refractory myeloma, a high number of whom had poor prognostic features at baseline, were treated with Elrexfio by 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, 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, and 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 DoR had not been reached; 18-month rate of DoR was 68.8% and 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.
Elrexfio administration, dosing, and schedule
Elrexfio is intended for 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
Table 1. Elrexfio dosing schedule
*Patients are premedicated for step-up doses on Days 1 and 4, as well as for the first treatment dose on Day 8.
for both step-up doses on Days 1 and 4, as well as for the first treatment dose on Day 8. Premedication includes:
¡ 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 step-up dosing schedule is as follows:
¡ Day 1, step-up dose = 12 mg of Elrexfio
¡ Day 4, step-up dose = 32 mg of Elrexfio
¡ Day 8, first treatment dose = 76 mg of Elrexfio
Elrexfio is administered at the dose of 76 mg once weekly for 24 weeks, then 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.
You 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.
Warnings and precautions
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.
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.
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
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.
In closing
This booklet is not meant to replace the advice of your doctors and nurses who are best able to answer questions about your specific healthcare management plan. The IMF intends only to provide you with information that will guide you in discussions with your healthcare team.
To help ensure a good quality of life through effective treatment of your myeloma, you must play an active role in your own medical care. We encourage you to visit myeloma.org for more information and to join the Myeloma Knowledge Platform at myprofile.myeloma.org.
To receive the most up-to-date information about myeloma in a caring and compassionate manner, call the IMF InfoLine at 1.818.487.7455, email InfoLine@myeloma.org, or schedule a time to talk with an IMF InfoLine Coordinator at mmsm.link/infoline.
To get answers to your questions without having to wait, ask Myelo® anytime 24/7 at myeloma.org. This generative AI assistant is designed to help you find the right resources.
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The International Myeloma Foundation (IMF) is the global leader in myeloma. Our mission is to improve the quality of life of myeloma patients while working toward prevention and a cure. Since 1990, the IMF has been serving the myeloma community through the following four pillars:
RESEARCH At the IMF, finding a cure for myeloma is our top priority. The IMF Scientific Advisory Board (SAB) of leading myeloma experts identifies key opportunities to drive research forward. The IMF Black Swan Research Initiative® (BSRI®) is pushing the boundaries with early screening for a precursor condition of myeloma as well as cure-focused myeloma clinical trials. The IMF International Myeloma Working Group (IMWG) provides trusted guidelines for diagnosing, treating, and managing myeloma. We also fund innovative research through the IMF Brian D. Novis Research Grants.
EDUCATION Myeloma is a complex and unique journey for each patient. The IMF offers hundreds of videos and free publications in multiple languages to inform and empower patients and care partners to navigate their myeloma journey. All IMF seminars, webinars, and workshops are free-of-charge and designed to directly connect the patient community with expert myeloma clinicians. The IMF Nurse Leadership Board (NLB) provides recommendations for the management of myeloma. The IMF M-Power Project works to break down barriers and ensure health equity in underserved populations.
SUPPORT Studies show that social support can greatly improve the quality of life of people with cancer. The IMF offers more than 160 myeloma support groups across North America, including specialized groups for Spanish-speakers, people with smoldering myeloma, care partners of patients with myeloma, and patients who do not have care partners. The IMF InfoLine answers myeloma-related questions. Myelo®, the IMF’s generative AI assistant, is available 24/7 to help you find the right resources.
ADVOCACY In the U.S., the IMF Advocacy team represents your interests at the federal and state levels. Internationally, the IMF Global Myeloma Action Network (GMAN) works to improve patient access to treatments.