ELREXFIO® (elranatamab-bcmm) 6 ADVERSE REACTIONS

(elranatamab-bcmm)

Prescribing Information

6 ADVERSE REACTIONS

The following adverse reactions are discussed elsewhere in labeling:

•: Cytokine Release Syndrome [see Warnings and Precautions (5.1)].
•: Neurologic Toxicity, Including ICANS [see Warnings and Precautions (5.2)].
•: Infections [see Warnings and Precautions (5.4)].
•: Neutropenia [see Warnings and Precautions (5.5)].
•: Hepatotoxicity [see Warnings and Precautions (5.6)].

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Relapsed/Refractory Multiple Myeloma

MagnetisMM-3

The safety of ELREXFIO was evaluated in MagnetisMM-3 [see Clinical Studies (14)]. The safety population described (n = 183) includes patients who received the recommended dosage regimen of 12 mg subcutaneously on Day 1, 32 mg on Day 4, and 76 mg once weekly starting on Day 8. Among patients who received ELREXFIO, 42% were exposed for 6 months or longer and 9% were exposed for one year or longer.

The median age of patients who received ELREXFIO was 68 years (range: 36 to 88 years); 48% were female; 61% were White, 10% were Hispanic/Latino, 9% were Asian, and 6% were Black or African American.

Serious adverse reactions occurred in 68% of patients who received ELREXFIO at the recommended dosing schedule. Serious adverse reactions in >2% of patients included pneumonia (25%), sepsis (13%), CRS (13%), upper respiratory tract infection (4.4%), acute kidney injury (3.8%), urinary tract infection (3.3%), COVID-19 (3.3%), encephalopathy (3.3%), pyrexia (2.2%), and febrile neutropenia (2.2%). Fatal adverse reactions occurred in 10% of patients including pneumonia (3.3%), sepsis (2.7%), acute respiratory distress syndrome (0.5%), cardio-respiratory arrest (0.5%), cardiogenic shock (0.5%), cardiopulmonary failure (0.5%), COVID-19 (0.5%), failure to thrive (0.5%), and pulmonary embolism (0.5%).

Permanent discontinuations of ELREXFIO due to an adverse reaction occurred in 17% of patients. Adverse reactions which resulted in permanent discontinuation of ELREXFIO in >2% of patients included septic shock (2.2%).

Dosage interruptions of ELREXFIO due to an adverse reaction occurred in 73% of patients. Adverse reactions which resulted in dose interruptions of ELREXFIO in >5% of patients included neutropenia, pneumonia, COVID-19, upper respiratory tract infection, thrombocytopenia, and anemia.

The most common adverse reactions (≥20%) were CRS, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia. The most common Grade 3 to 4 laboratory abnormalities (≥30%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets.

Table 8 summarizes adverse reactions in MagnetisMM-3.

Table 8. Adverse Reactions (≥10%) in Patients with Relapsed or Refractory Multiple Myeloma Who Received ELREXFIO in MagnetisMM-3
Adverse reactions were graded based on CTCAE Version 5.0, with the exception of CRS, which was graded based on the ASTCT 2019 criteria.
* Only grade 3 adverse reactions occurred. † Includes other related terms. ‡ Pneumonia includes COVID-19 pneumonia, lower respiratory tract infection, lower respiratory tract infection viral, pneumocystis jirovecii pneumonia, pneumonia, pneumonia adenoviral, pneumonia bacterial, pneumonia cytomegaloviral, pneumonia fungal, pneumonia influenzal, pneumonia pseudomonal, pneumonia viral. § Sepsis includes bacteremia, device related bacteremia, device related sepsis, escherichia bacteremia, escherichia sepsis, klebsiella sepsis, pseudomonal sepsis, sepsis, septic shock, staphylococcal bacteremia, staphylococcal sepsis, streptococcal sepsis, urosepsis. ¶ Rash incudes erythema, palmar-plantar erythrodysesthesia syndrome, rash, rash erythematous, rash macular, rash maculo-papular, rash pustular, symmetrical drug-related intertriginous and flexural exanthema. # Encephalopathy includes agitation, altered state of consciousness, cognitive disorder, confusional state, delirium, depressed level of consciousness, disorientation, hallucination, lethargy, memory impairment, metabolic encephalopathy, somnolence, toxic encephalopathy. Þ Sensory neuropathy includes burning sensation, dysesthesia, hypoesthesia, neuropathy peripheral, paresthesia, parosmia, peripheral sensorimotor neuropathy, peripheral sensory neuropathy, polyneuropathy, sensory loss. ß Motor dysfunction includes ataxia, balance disorder, gait disturbance, motor dysfunction, muscle contracture, muscle spasms, muscular weakness, peripheral motor neuropathy, peroneal nerve palsy, tremor.
System Organ Class Preferred Term	ELREXFIO N = 183
	All Grades (%)	Grade 3 or 4 (%)
Immune system disorders
Cytokine release syndrome	58	0.5*
Hypogammaglobulinemia†	13	2.2*
General disorders and site administration conditions
Fatigue†	43	6*
Injection site reaction†	37	0
Pyrexia	21	2.7*
Edema†	18	1.1*
Gastrointestinal disorders
Diarrhea	36	1.1*
Nausea	21	0
Constipation	14	0
Vomiting	14	0
Infections
Upper respiratory tract infection†	36	4.9
Pneumonia‡	32	19
Sepsis§	15	11
Urinary tract infection†	12	4.4*
Musculoskeletal and connective tissue disorders
Musculoskeletal pain†	34	2.7*
Metabolism and nutrition disorders
Decreased appetite	26	1.1*
Skin and Subcutaneous Tissue disorders
Rash¶	26	0
Dry skin	14	0
Skin exfoliation†	10	0
Respiratory, thoracic and mediastinal disorders
Cough†	24	0
Dyspnea†	15	3.3*
Nervous system disorders
Headache	18	0
Encephalopathy#	14	2.2
Sensory neuropathyÞ	13	0.5*
Motor dysfunctionß	14	1.1*
Cardiac disorders
Cardiac arrhythmia†	16	1.6
Vascular disorders
Hemorrhage†	13	1.6
Psychiatric disorders
Insomnia	13	0
Injury, poisoning and procedural complications
Fall	10	0.5*

Clinically relevant adverse reactions in <10% of patients who received ELREXFIO included ICANS, febrile neutropenia, Guillain-Barré syndrome, abdominal pain, acute kidney injury, COVID-19, cardiac failure, congestion, thrombosis, cytomegalovirus infection, and progressive multifocal leukoencephalopathy.

Table 9 summarizes laboratory abnormalities in MagnetisMM-3.

Table 9. Select Laboratory Abnormalities (≥30%) That Worsened from Baseline in Patients with Relapsed or Refractory Multiple Myeloma Who Received ELREXFIO in MagnetisMM-3*
* Laboratory tests were graded according to NCI-CTCAE Version 5.0. † The denominator used to calculate the rate varied from 181 to 183 based on the number of patients with a baseline value and at least one post-treatment value.
Laboratory Abnormality	ELREXFIO†
Laboratory Abnormality	All Grades (%)	Grade 3 or 4 (%)
Hematology
Lymphocyte count decreased	91	84
White blood cell decreased	69	40
Hemoglobin decreased	68	43
Neutrophil count decreased	62	51
Platelet count decreased	61	32
Chemistry
Albumin decreased	55	6
AST increase	40	6
Creatinine increased	38	3.3
Potassium decreased	36	8
ALT increase	36	3.8
Alkaline phosphatase increased	34	1.1
Creatinine clearance decreased	32	10

Medication Guide

MEDICATION GUIDE

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: Feb 2026
MEDICATION GUIDE ELREXFIO® (el-reks-fe-o) (elranatamab-bcmm) injection, for subcutaneous use
What is the most important information I should know about ELREXFIO? ELREXFIO may cause serious side effects, including: • Cytokine Release Syndrome (CRS). CRS is common during treatment with ELREXFIO and can also be serious, life-threatening, or can lead to death. Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of CRS, including:
	o fever of 100.4 °F (38 °C) or higher o trouble breathing o chills o dizziness or light-headedness o fast heartbeat		o headache o increased liver enzymes in your blood. See “What are the possible side effects of ELREXFIO?” for more information about the signs and symptoms of liver problems.
Due to the risk of CRS, you will receive ELREXFIO on a “step-up dosing schedule” and should be hospitalized for 48 hours after the first “step-up” dose and for 24 hours after the second “step-up” dose of ELREXFIO. o During the step-up dosing schedule: ▪ for your first dose, you will receive a smaller “step-up” dose of ELREXFIO on Day 1 of your treatment ▪ for your second dose, you will receive a larger “step-up” dose of ELREXFIO, which is usually given on Day 4 of your treatment ▪ for your third dose, you will receive the first full “treatment” dose of ELREXFIO, which is usually given on Day 8 of your treatment o If your dose of ELREXFIO is delayed for any reason, you may need to repeat the step-up dosing schedule. o Before each step-up dose and the first full treatment dose of ELREXFIO, you will receive medicines to help reduce your risk of CRS. Your healthcare provider will decide if you need to receive medicines to help reduce your risk of CRS with future doses. o See “How will I receive ELREXFIO?” for more information about how you will receive ELREXFIO. • Neurologic problems. ELREXFIO can cause neurologic problems that can be serious or life-threatening. Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of neurologic problems, including:
	o headache o agitation, trouble staying awake, confusion or disorientation, seeing or hearing things that are not real (hallucinations) o trouble speaking, thinking, remembering things, paying attention, or understanding things		o problems walking, muscle weakness, shaking (tremors), loss of balance, or muscle spasms o numbness and tingling (feeling like “pins and needles”) o burning, throbbing, or stabbing pain o changes in your handwriting
• ELREXFIO is available only through the ELREXFIO Risk Evaluation and Mitigation Strategy (REMS) due to the risk of CRS and neurologic problems. You will receive an ELREXFIO Patient Wallet Card from your healthcare provider. Carry the ELREXFIO Patient Wallet Card with you at all times and show it to all of your healthcare providers. The ELREXFIO Patient Wallet Card lists symptoms of CRS and neurologic problems. Get medical help right away if you develop any of the symptoms listed on the ELREXFIO Patient Wallet Card. You may need to be treated in a hospital. Your healthcare provider will monitor you for signs and symptoms of CRS and neurologic problems during treatment with ELREXFIO, as well as other side effects, and will treat you if needed. Your healthcare provider may temporarily stop or completely stop your treatment with ELREXFIO if you develop CRS, neurologic problems, or any other side effects that are severe. If you have any questions about ELREXFIO, ask your healthcare provider. See “What are possible side effects of ELREXFIO?” for more information about side effects.
What is ELREXFIO? ELREXFIO is a prescription medicine used to treat adults with multiple myeloma who: • have already received at least 4 treatment regimens, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody to treat their multiple myeloma, and • their cancer has come back or did not respond to prior treatment. It is not known if ELREXFIO is safe and effective in children.
Before receiving ELREXFIO, tell your healthcare provider about all of your medical conditions, including if you: • have an infection. • are pregnant or plan to become pregnant. ELREXFIO may harm your unborn baby. Females who are able to become pregnant: o Your healthcare provider should do a pregnancy test before you start treatment with ELREXFIO. o You should use effective birth control (contraception) during treatment and for 4 months after your last dose of ELREXFIO. o Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with ELREXFIO. • are breastfeeding or plan to breastfeed. It is not known if ELREXFIO passes into your breast milk. Do not breastfeed during treatment and for 4 months after your last dose of ELREXFIO. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
How will I receive ELREXFIO? • ELREXFIO will be given to you by your healthcare provider as an injection under your skin (subcutaneous injection), usually in your stomach-area (abdomen). Your thigh or another area of your body may also be used. • See “What is the most important information I should know about ELREXFIO?” for more information about how you will receive ELREXFIO. • After you receive your first full “treatment” dose, ELREXFIO is usually given 1 time each week through Week 24. • Starting on Week 25, your future doses will usually be given 1 time every 2 weeks. • Starting on Week 49, your future doses will usually be given 1 time every 4 weeks. • Your healthcare provider will decide the time between doses and how long you will receive treatment with ELREXFIO. If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. It is important for you to be monitored closely for side effects during treatment with ELREXFIO.
What should I avoid while receiving ELREXFIO? Do not drive, operate heavy or potentially dangerous machinery, or do other dangerous activities during treatment with ELREXFIO: • for 48 hours after completing each of the 2 doses of ELREXFIO that are part of the “step-up dosing schedule” and your first full treatment dose, and • at any time during treatment with ELREXFIO if you develop any new neurologic symptoms such as dizziness, confusion, shaking (tremors), sleepiness, or any other symptom that impairs consciousness, until the symptoms go away. See “What is the most important information I should know about ELREXFIO?” for more information about signs and symptoms of neurologic problems.
What are the possible side effects of ELREXFIO? ELREXFIO may cause serious side effects, including: • See “What is the most important information I should know about ELREXFIO?” • Infections. Upper respiratory tract infections and pneumonia are common during treatment with ELREXFIO. ELREXFIO can cause bacterial and viral infections that are severe, life-threatening, or that may lead to death. o Your healthcare provider may prescribe medicines for you to help prevent infections and treat you as needed if you develop an infection during treatment with ELREXFIO. o Tell your healthcare provider right away if you develop any signs or symptoms of an infection during treatment with ELREXFIO, including:
		▪ fever of 100.4 °F (38 °C) or higher ▪ chills ▪ cough ▪ shortness of breath	▪ chest pain ▪ sore throat ▪ pain during urination ▪ feeling weak or generally unwell
• Decreased white blood cell counts. Decreased white blood cell counts are common during treatment with ELREXFIO and can also be severe. Fever can happen with low white blood cell counts and may be a sign that you have an infection. Your healthcare provider will treat you as needed. • Liver problems. ELREXFIO can cause increased liver enzymes and bilirubin in your blood. These increases can happen with or without you also having CRS. Tell your healthcare provider if you develop any of the following signs or symptoms of liver problems:
	o tiredness o loss of appetite o pain in your right upper stomach-area (abdomen)		o dark urine o yellowing of your skin or the white part of your eyes
Your healthcare provider will check your blood and monitor you for signs and symptoms of these serious side effects before you start and during treatment with ELREXFIO and may temporarily or completely stop treatment with ELREXFIO if you develop certain side effects. The most common side effects of ELREXFIO include:
	• tiredness • injection site reaction, such as redness, itching, pain, bruising, rash, swelling, tenderness • diarrhea • muscle and bone pain		• decreased appetite • rash • cough • nausea • fever
The most common severe abnormal blood test results with ELREXFIO include decreased white blood cells, red blood cells, and platelets. These are not all of the possible side effects of ELREXFIO. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
General information about the safe and effective use of ELREXFIO. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. You can ask your pharmacist or healthcare provider for more information about ELREXFIO that is written for health professionals.
What are the ingredients in ELREXFIO? Active ingredient: elranatamab-bcmm Inactive ingredients: edetate disodium, histidine, L-histidine hydrochloride monohydrate, polysorbate 80, sucrose, and Water for Injection Manufactured by: Pfizer Inc., NY, NY 10001 US License No. 2001 LAB-1551-3.0 For more information on ELREXFIO, go to www.ELREXFIO.com For more information on Pfizer, go to www.Pfizer.com or call 1-800-438-1985

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