ELREXFIO (Elranatamab): Uses, Dosage & Side Effects
Bispecific T-cell engager antibody for relapsed or refractory multiple myeloma
ELREXFIO (elranatamab) is a bispecific T-cell engager antibody used to treat adults with relapsed or refractory multiple myeloma who have received at least three prior therapies. It works by simultaneously binding to BCMA on myeloma cells and CD3 on T-cells, redirecting the immune system to destroy cancer cells. ELREXFIO is administered as a subcutaneous injection in a clinical setting, with mandatory 48-hour monitoring after the first two doses due to risk of cytokine release syndrome (CRS).
Quick Facts
Key Takeaways
- ELREXFIO is a bispecific antibody targeting BCMA and CD3, approved for adults with relapsed or refractory multiple myeloma after at least three prior therapies
- Treatment starts with two step-up doses (12 mg and 32 mg) to reduce the risk of severe cytokine release syndrome (CRS), followed by weekly 76 mg doses
- Patients must remain near a healthcare facility for 48 hours after each of the first two step-up doses for CRS and ICANS monitoring
- Common serious side effects include CRS, infections, neutropenia, and hypogammaglobulinemia; premedication with corticosteroids, antihistamines, and antipyretics is required
- Dosing frequency may be reduced to every two weeks after Week 24 and every four weeks after Week 48 in patients with sustained response
What Is ELREXFIO and What Is It Used For?
ELREXFIO is a cancer medicine containing the active substance elranatamab. It is indicated for the treatment of adult patients with multiple myeloma, a type of cancer that develops in the bone marrow from plasma cells. Specifically, ELREXFIO is used in patients whose cancer has returned (relapsed) and has stopped responding to previous treatments (refractory), and who have received at least three prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.
Multiple myeloma is the second most common hematologic malignancy, with approximately 176,000 new cases diagnosed worldwide each year according to the World Health Organization (WHO). Despite significant advances in treatment over the past two decades, most patients will eventually relapse and develop resistance to available therapies. For patients who have exhausted standard treatment options, novel targeted immunotherapies such as ELREXFIO represent an important therapeutic advance.
How ELREXFIO Works
ELREXFIO is a bispecific antibody — a type of protein engineered to recognize and attach to two specific targets in the body simultaneously. One arm of the antibody binds to BCMA (B-cell maturation antigen), a protein found on the surface of myeloma cells. The other arm binds to CD3 (cluster of differentiation 3), a protein found on T-lymphocytes, a type of white blood cell that is a key part of the immune system.
By binding to both targets at the same time, ELREXFIO physically brings cancer cells and T-cells into close proximity, creating an immunological synapse. This activates the T-cells and redirects them to kill the myeloma cells. This mechanism of action is fundamentally different from traditional chemotherapy, as it harnesses the patient's own immune system to fight the cancer rather than directly poisoning cancer cells.
The BCMA target is particularly well-suited for multiple myeloma treatment because it is highly expressed on myeloma cells and mature B-cells, but has limited expression on other cell types. This selectivity helps concentrate the immune attack on cancer cells while reducing off-target effects. Clinical trials have demonstrated that ELREXFIO achieves overall response rates of approximately 61% in heavily pretreated patients, with some patients achieving deep, durable responses.
ELREXFIO was granted conditional marketing authorization by the European Medicines Agency (EMA) and accelerated approval by the U.S. Food and Drug Administration (FDA), reflecting the urgent unmet medical need for effective treatments in this patient population. The conditional approval means that additional data from ongoing confirmatory trials are expected.
What Should You Know Before Taking ELREXFIO?
ELREXFIO is a powerful immunotherapy that requires careful patient selection and thorough pre-treatment evaluation. Before beginning treatment, it is essential that your healthcare team has a complete understanding of your medical history, current medications, and overall health status. The risk-benefit balance must be individually assessed for each patient, taking into account the severity of the disease, available alternatives, and the patient's ability to be closely monitored during the critical initial treatment period.
Contraindications
ELREXFIO should not be given to patients who have a known allergy (hypersensitivity) to elranatamab or any of the other ingredients in the medicine. If you are unsure whether you have any allergies to the components of ELREXFIO, speak with your doctor or nurse before receiving the injection. The excipients include disodium edetate, L-histidine, L-histidine hydrochloride monohydrate, polysorbate 80, sucrose, and water for injections.
Warnings and Precautions
Tell your doctor or nurse about all of your medical conditions before receiving ELREXFIO, including any recent infections. Be particularly alert for the following serious adverse reactions:
CRS is a serious immune reaction that can occur when T-cells are activated by ELREXFIO. Symptoms include fever, difficulty breathing, chills, headache, low blood pressure, rapid heartbeat, dizziness, and elevated liver enzymes. CRS occurred in approximately 58% of patients in clinical trials, most commonly during the step-up doses. Seek immediate medical attention if you experience any of these symptoms.
ICANS is a serious neurological complication that can occur with T-cell engaging therapies. Symptoms include confusion, reduced alertness, difficulty speaking or writing, and disorientation. ICANS occurred in approximately 3% of patients treated with ELREXFIO. Report any neurological symptoms to your healthcare team immediately.
ELREXFIO can weaken the immune system and increase the risk of severe, potentially life-threatening infections including pneumonia and sepsis. Signs include fever, chills, fatigue, and difficulty breathing. Your doctor will monitor your blood counts regularly and may prescribe prophylactic antimicrobial medications.
Your doctor will monitor you for signs and symptoms of CRS and ICANS for 48 hours after each of the first two step-up doses. You must remain near a healthcare facility during this monitoring period. Blood tests will be performed regularly throughout treatment to monitor your blood cell counts and other parameters, as ELREXFIO can cause significant decreases in neutrophils, lymphocytes, and immunoglobulin levels.
Vaccinations
Speak with your doctor before receiving ELREXFIO if you have recently been vaccinated or plan to receive any vaccines. You should not receive live vaccines within four weeks before the first dose of ELREXFIO, during treatment, and for at least four weeks after the last dose. Inactivated vaccines may be administered, but their effectiveness may be reduced due to ELREXFIO's immunosuppressive effects.
Pregnancy and Breastfeeding
ELREXFIO is not recommended during pregnancy. It is not known whether elranatamab can cause harm to an unborn baby. Given its mechanism of action as a T-cell engaging therapy, there is a theoretical risk of fetal harm through immune-mediated effects. Women of childbearing potential should have a pregnancy test before starting treatment.
If you are able to become pregnant, you must use effective contraception during treatment and for at least 6 months after the last dose of ELREXFIO. If you become pregnant during treatment, inform your doctor or nurse immediately.
You should not breastfeed during treatment with ELREXFIO and for at least 6 months after the last dose. It is not known whether elranatamab passes into breast milk or what effects it might have on a breastfed infant.
Driving and Operating Machinery
Some patients may experience tiredness, dizziness, or confusion when receiving ELREXFIO. Do not drive or operate machinery until at least 48 hours after each of the two step-up doses, and not until your symptoms have improved. Follow your healthcare provider's guidance regarding when it is safe to resume these activities.
Use in Children and Adolescents
ELREXFIO is not intended for use in children or adolescents under 18 years of age. The safety and efficacy of elranatamab have not been established in the pediatric population, and multiple myeloma is extremely rare in this age group.
How Does ELREXFIO Interact with Other Drugs?
Tell your doctor or nurse about all medications you are taking, have recently taken, or plan to take, including prescription medicines, over-the-counter drugs, and herbal or complementary remedies. While formal drug-drug interaction studies have not been conducted with ELREXFIO, the cytokine release associated with T-cell engaging therapies can suppress the activity of cytochrome P450 (CYP) enzymes, particularly CYP3A4, CYP1A2, CYP2C9, and CYP2D6. This suppression may lead to increased plasma concentrations of drugs metabolized by these enzymes.
This effect is particularly important during the first weeks of treatment when CRS is most likely to occur. Once cytokine levels normalize, CYP enzyme activity typically returns to baseline, which could then lead to reduced efficacy of concomitant medications. Patients taking medications with a narrow therapeutic index should be closely monitored, and dose adjustments may be necessary.
| Interacting Drug | Type | Mechanism | Clinical Significance |
|---|---|---|---|
| Cyclosporine | CYP3A4 substrate | CRS-mediated CYP3A4 suppression may increase cyclosporine levels | Monitor levels closely during CRS episodes |
| Warfarin | CYP2C9 substrate | CRS-mediated CYP2C9 suppression may alter INR | Monitor INR frequently; adjust dose as needed |
| Phenytoin | CYP2C9/CYP2C19 substrate | CRS-mediated CYP suppression may increase phenytoin levels | Monitor phenytoin levels; risk of toxicity |
| Sirolimus | CYP3A4 substrate | CRS-mediated CYP3A4 suppression may increase sirolimus levels | Monitor trough levels; adjust dose during CRS |
| Live vaccines | Contraindicated | Immunosuppression may lead to vaccine-strain infection | Avoid 4 weeks before, during, and 4 weeks after treatment |
The interaction risk is highest during the initial step-up dosing period and whenever CRS occurs. After cytokine levels normalize, the risk decreases. Always inform all healthcare providers involved in your care that you are receiving ELREXFIO, especially before starting any new medication or undergoing surgery.
What Is the Correct Dosage of ELREXFIO?
ELREXFIO is always administered under the supervision of healthcare professionals experienced in cancer treatment. The step-up dosing approach is specifically designed to reduce the severity of cytokine release syndrome by gradually increasing T-cell activation. The full treatment dose of 76 mg is not reached until Week 2 of treatment.
Step-Up Dosing Schedule
| Treatment Phase | Dose | Frequency | Volume |
|---|---|---|---|
| Step-up Dose 1 (Week 1, Day 1) | 12 mg | Single dose | 0.3 mL |
| Step-up Dose 2 (Week 1, Day 4) | 32 mg | Single dose | 0.8 mL |
| Full dose (Week 2–24) | 76 mg | Once weekly | 1.9 mL |
| Extended dosing (Week 25–48) | 76 mg | Every 2 weeks* | 1.9 mL |
| Maintenance (Week 49+) | 76 mg | Every 4 weeks* | 1.9 mL |
*Dose frequency reduction from weekly to every 2 weeks (after Week 24) and to every 4 weeks (after Week 48) is permitted only in patients whose cancer continues to respond to treatment. Your physician will determine the appropriate dosing interval based on your individual disease response.
Administration
ELREXFIO is always given by a doctor or nurse as a subcutaneous injection (under the skin). The injection is administered in the abdomen (preferred site) or the thigh. The injection site should be rotated, and ELREXFIO should not be injected into areas where the skin is bruised, red, tender, hard, or scarred.
You may experience injection site reactions including redness, pain, swelling, bruising, rash, itching, or bleeding at the injection site. These reactions are generally mild and resolve on their own without treatment.
Premedication
Before each of the first three doses of ELREXFIO, you will receive premedication approximately one hour before the injection. These medications are given to reduce the risk and severity of CRS and include:
- Antipyretics (e.g., paracetamol/acetaminophen) to reduce fever risk
- Corticosteroids (e.g., dexamethasone) to reduce inflammation
- Antihistamines (e.g., diphenhydramine) to reduce allergic reaction risk
Your healthcare team may also administer these premedications before subsequent doses based on any symptoms you experienced after previous injections.
Missed Dose
It is very important to attend all scheduled treatment appointments for your therapy to work effectively. If you miss a treatment session, contact your healthcare team to schedule a new appointment as soon as possible. Your doctor will determine how to adjust your treatment schedule based on how long since your last dose.
Overdose
Since ELREXFIO is administered by healthcare professionals in a clinical setting, overdose is unlikely. In the event of an accidental overdose, your doctor will monitor you for any adverse effects, particularly signs and symptoms of CRS and ICANS, and provide supportive care as needed.
What Are the Side Effects of ELREXFIO?
Like all medicines, ELREXFIO can cause side effects, although not everyone experiences them. The side effects reflect ELREXFIO's mechanism of action as a T-cell engaging therapy, which activates the immune system. Some side effects can be serious and potentially life-threatening, so it is essential to recognize them early and seek prompt medical attention.
The frequency of side effects is classified according to the following convention: Very common (may affect more than 1 in 10 people), Common (may affect up to 1 in 10 people), Uncommon (may affect up to 1 in 100 people). Your healthcare team will monitor you closely throughout treatment and adjust your care plan as needed to manage any side effects that occur.
Serious Side Effects
Seek immediate medical attention if you experience any of the following serious side effects. These can be severe and potentially life-threatening:
Very Common (>1 in 10 patients)
- Cytokine release syndrome (CRS) — fever, difficulty breathing, chills, dizziness, rapid heartbeat, elevated liver enzymes
- Neutropenia — low levels of neutrophils (a type of white blood cell that fights infection)
- Hypogammaglobulinemia — low levels of immunoglobulins (antibodies) in the blood, increasing infection risk
- Infections — including fever, chills, fatigue, difficulty breathing; may include pneumonia and sepsis
Common (1 in 10 to 1 in 100 patients)
- ICANS — immune effector cell-associated neurotoxicity syndrome causing confusion, reduced alertness, difficulty speaking or writing
Uncommon (1 in 100 to 1 in 1,000 patients)
- Progressive multifocal leukoencephalopathy (PML) — a serious and potentially fatal brain infection causing blurred vision, difficulty speaking, weakness in limbs, balance problems, numbness, memory loss, or confusion
Other Side Effects
Very Common (>1 in 10 patients)
- Anemia (low red blood cell counts)
- Fatigue or weakness
- Upper respiratory tract infection (nose or throat infection)
- Injection site reactions (redness, itching, swelling, pain, bruising, rash, bleeding)
- Diarrhea
- Pneumonia (lung infection)
- Thrombocytopenia (low platelet counts)
- Lymphopenia (low lymphocyte counts)
- Fever (pyrexia)
- Decreased appetite
- Rash
- Dry skin
- Joint pain (arthralgia)
- Hypokalemia (low potassium levels)
- Nausea
- Headache
- Difficulty breathing (dyspnea)
- Sepsis (blood infection)
- Leukopenia (low white blood cell counts)
- Elevated liver enzymes (transaminases)
- Peripheral neuropathy (nerve damage causing tingling, numbness, pain, or loss of sensation in hands/feet)
- Urinary tract infection
Common (1 in 10 to 1 in 100 patients)
- Hypophosphatemia (low phosphate levels in the blood)
- Febrile neutropenia (low neutrophil count with fever)
It is important to report suspected side effects after the medicine has been authorized, as this allows ongoing monitoring of the medicine's benefit-risk balance. Healthcare professionals and patients are encouraged to report any suspected adverse reactions to their national pharmacovigilance authority (e.g., FDA MedWatch in the United States, Yellow Card Scheme in the United Kingdom, or the EMA in the European Union).
How Should ELREXFIO Be Stored?
ELREXFIO is stored and administered at the hospital or clinic by your healthcare team. You will not need to handle or store this medicine yourself. However, it is useful to understand the storage requirements, as they reflect the biological nature of the medicine and the importance of maintaining its integrity.
The medicine must be stored in a refrigerator at 2–8°C and must not be frozen. It should be kept in the original packaging to protect it from light. ELREXFIO should not be used after the expiry date printed on the carton and vial label.
After opening the vial, including storage in prepared syringes under aseptic conditions, ELREXFIO is stable for up to 7 days at 2–8°C and up to 24 hours at room temperature (up to 30°C). The medicine should not be used if the solution shows signs of discoloration or contains visible particles. ELREXFIO solution should appear clear to slightly opalescent and colorless to slightly brownish.
Vials are for single use only. Any unused medicine or waste should be disposed of in accordance with local institutional requirements and applicable regulations for cytotoxic/biohazardous waste.
What Does ELREXFIO Contain?
ELREXFIO is available as a ready-to-use solution for injection that does not require dilution before administration. Each package contains one glass vial. The medicine is available in two presentations:
| Vial Size | Total Content | Concentration | Primary Use |
|---|---|---|---|
| 1.1 mL vial | 44 mg elranatamab | 40 mg/mL | Step-up doses (12 mg or 32 mg) |
| 1.9 mL vial | 76 mg elranatamab | 40 mg/mL | Full treatment dose (76 mg) |
Inactive Ingredients (Excipients)
- Disodium edetate — a chelating agent that helps stabilize the protein
- L-histidine — an amino acid used as a buffering agent
- L-histidine hydrochloride monohydrate — helps maintain the correct pH
- Polysorbate 80 — a surfactant that prevents protein aggregation
- Sucrose — a stabilizing sugar that protects the antibody structure
- Water for injections — the solvent
ELREXFIO contains less than 1 mmol (23 mg) of sodium per dose, meaning it is essentially sodium-free. This is important information for patients on a controlled sodium diet.
The marketing authorization holder is Pfizer Europe MA EEIG, Brussels, Belgium. The medicine is manufactured by Pfizer Service Company BV, Zaventem, Belgium.
Frequently Asked Questions About ELREXFIO
ELREXFIO (elranatamab) is used to treat adults with relapsed or refractory multiple myeloma who have received at least three prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody. It is a bispecific T-cell engager antibody that targets BCMA on myeloma cells and CD3 on T-cells, activating the patient's own immune system to destroy cancer cells.
Cytokine release syndrome (CRS) is a serious immune reaction caused by the rapid activation of T-cells. Symptoms include fever, difficulty breathing, chills, low blood pressure, rapid heartbeat, and dizziness. CRS occurred in approximately 58% of patients treated with ELREXFIO, primarily during the step-up dosing phase. To reduce risk, patients receive premedication before the first three doses and are monitored for 48 hours after each of the first two step-up doses. Most CRS events are manageable with supportive care, including tocilizumab and corticosteroids for more severe cases.
ELREXFIO treatment continues as long as the patient benefits from it and it is tolerated. Initially, it is given weekly (after the step-up doses). After Week 24, if the cancer is responding, the frequency may be reduced to every two weeks. After Week 48, it may be further reduced to every four weeks. There is no predetermined maximum treatment duration — your oncologist will assess your response regularly and make treatment decisions based on your individual situation.
Live vaccines are contraindicated within four weeks before starting ELREXFIO, during treatment, and for at least four weeks after the last dose. This is because ELREXFIO suppresses the immune system, and live vaccines contain weakened but viable organisms that could potentially cause infection in immunocompromised patients. Inactivated vaccines (such as influenza and COVID-19 vaccines) may be given, but their effectiveness may be reduced. Discuss your vaccination schedule with your oncologist.
No. While both ELREXFIO and CAR-T cell therapy target BCMA on myeloma cells and both engage T-cells, they work differently. CAR-T therapy involves collecting a patient's T-cells, genetically modifying them in a laboratory, and infusing them back into the patient. ELREXFIO is an off-the-shelf bispecific antibody that redirects the patient's existing T-cells without genetic modification. ELREXFIO is administered as a subcutaneous injection, whereas CAR-T requires a complex manufacturing process and intravenous infusion. Both share similar risks including CRS and ICANS.
If you miss a scheduled appointment for ELREXFIO, contact your healthcare team as soon as possible to reschedule. It is important to maintain your treatment schedule for optimal effectiveness. Your doctor will determine the appropriate next steps based on how much time has elapsed since your last dose and your current disease status. Do not attempt to make up for missed doses on your own.
References
All medical information on this page is based on peer-reviewed research, regulatory documents, and international clinical guidelines. The following sources were consulted:
- European Medicines Agency (EMA). ELREXFIO (elranatamab) — EPAR Summary of Product Characteristics. Available at: www.ema.europa.eu. Last updated 2025.
- U.S. Food and Drug Administration (FDA). ELREXFIO Prescribing Information. Approved August 2023.
- Lesokhin AM, Tomasson MH, Arnulf B, et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. N Engl J Med. 2023;389(11):1009-1022.
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Multiple Myeloma. Version 3.2025.
- European Society for Medical Oncology (ESMO). Multiple Myeloma: ESMO Clinical Practice Guidelines. Ann Oncol. 2024.
- World Health Organization (WHO). Global Cancer Observatory: Multiple Myeloma Fact Sheet. Available at: www.who.int.
- British National Formulary (BNF). Elranatamab. Available at: bnf.nice.org.uk.
- Lee DW, Santomasso BD, Locke FL, et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019;25(4):625-638.
About Our Medical Editorial Team
This article has been written and reviewed by iMedic's medical editorial team, which includes board-certified specialists in hematology-oncology with extensive clinical experience in the management of multiple myeloma and novel immunotherapies.
Content developed by licensed medical professionals with expertise in oncology pharmacology, clinical trial interpretation, and patient education. All medical claims are supported by peer-reviewed evidence at Level 1A (systematic reviews and randomized controlled trials).
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