ELREXFIO

Elranatamab-bcmm is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager. It is a bispecific, humanized immunoglobulin 2-alanine (IgG2Δa) kappa antibody derived from two monoclonal antibodies (mAbs), an anti-BCMA mAb and an anti-CD3 mAb. Each of these mAbs contributes one distinct heavy (H) chain and one distinct light (L) chain to the bispecific elranatamab-bcmm. The resulting 4-chain bispecific antibody is covalently linked via five inter-chain disulfide bonds. Elranatamab-bcmm is produced using two recombinant Chinese hamster ovary (CHO) cell lines, one that contains the DNA encoding the sequence for anti-BCMA monoclonal antibody (mAb) and one that contains the sequence for anti-CD3 mAb, which are grown separately in suspension culture using chemically-defined (CD), animal-derived component-free (ACF) media. The molecular weight of elranatamab-bcmm is approximately 148.5 kDa. ELREXFIO TM (elranatamab-bcmm) injection is a sterile, preservative-free, clear to slightly opalescent, and colorless to pale brown liquid solution for subcutaneous administration. ELREXFIO (elranatamab-bcmm) is supplied at a concentration of 40 mg/mL in either 76 mg/1.9 mL or 44 mg/1.1 mL single-dose vials. Each mL of solution contains 40 mg elranatamab-bcmm, edetate disodium (0.045 mg), histidine (1.12 mg), L-histidine hydrochloride monohydrate (2.67 mg), polysorbate 80 (0.2 mg), sucrose (85 mg) and Water for Injection. The pH is 5.8.

ELREXFIO is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. This indication is approved under accelerated approval based on response rate and durability of response [see Clinical Studies (14) ] . Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial(s). ELREXFIO is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T‑cell engager indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial(s). ( 1 )

ELREXFIO Dosing Schedule ( 2.2 ) Dosing Schedule Day ELREXFIO Dose Step-up Dosing Schedule Day 1 Step-up dose 1 12 mg Day 4 Step-up dose 2 32 mg Day 8 First treatment dose 76 mg Weekly Dosing Schedule One week after first treatment dose and weekly thereafter through week 24 Subsequent treatment doses 76 mg Biweekly (Every 2 Week) Dosing Schedule Responders only week 25 onward. Week 25 and every 2 weeks thereafter through week 48 Subsequent treatment doses 76 mg Every 4 Week Dosing Schedule In patients who have maintained the response following 24 weeks of treatment at the biweekly dosing schedule. Week 49 and every 4 weeks thereafter Subsequent treatment doses 76 mg • Patients should be hospitalized for 48 hours after administration of the first step-up dose, and for 24 hours after administration of the second step-up dose. ( 2.1 ) • For subcutaneous injection only. ( 2.2 ) • Administer pre-treatment medications as recommended. ( 2.3 ) • See Full Prescribing Information for instructions on preparation and administration. ( 2.6 ) 2.1 Important Dosing Information Administer ELREXFIO subcutaneously according to the step-up dosing schedule to reduce the incidence and severity of cytokine release syndrome (CRS). Administer pre-treatment medications prior to each dose in the ELREXFIO step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose as recommended [see Dosage and Administration (2.2 , 2.3 )] . ELREXFIO should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions such as CRS and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1 , 5.2 )] . Due to the risk of CRS, patients should be hospitalized for 48 hours after administration of the first step-up dose, and for 24 hours after administration of the second step-up dose. 2.2 Recommended Dosage For subcutaneous injection only. The recommended dosing schedule for ELREXFIO is provided in Table 1. The recommended dosages of ELREXFIO subcutaneous injection are: step-up dose 1 of 12 mg on Day 1, step-up dose 2 of 32 mg on Day 4, followed by the first treatment dose of 76 mg on Day 8, and then 76 mg weekly thereafter through week 24. For patients who have received at least 24 weeks of treatment with ELREXFIO and have achieved a response [partial response (PR) or better] and maintained this response for at least 2 months, the dose interval should transition to an every two-week schedule. For patients who have received at least 24 weeks of treatment with ELREXFIO at the every two-week dosing schedule and have maintained the response, the dose interval should transition to an every four-week schedule. Continue treatment with ELREXFIO until disease progression or unacceptable toxicity. Administer pre-treatment medications prior to each dose in the ELREXFIO step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose as recommended [see Dosage and Administration (2.3) ] . Table 1. ELREXFIO Dosing Schedule Note: See Table 2 for recommendations on restarting ELREXFIO after dose delays. Dosing Schedule Day ELREXFIO Dose Step-up Dosing Schedule Day 1 Administer pre-treatment medications prior to each dose in the ELREXFIO step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose [see Dosage and Administration (2.3) ] . Step-up dose 1 12 mg Day 4 A minimum of 2 days should be maintained between step-up dose 1 (12 mg) and step-up dose 2 (32 mg). Step-up dose 2 32 mg Day 8 A minimum of 3 days should be maintained between step-up dose 2 (32 mg) and the first treatment (76 mg) dose. First treatment dose 76 mg Weekly Dosing Schedule One week after first treatment dose and weekly thereafter A minimum of 6 days should be maintained between treatment doses. through week 24 Subsequent treatment doses 76 mg Biweekly (Every 2 Week) Dosing Schedule *Responders only week 25 onward Week 25 and every 2 weeks thereafter through week 48 Subsequent treatment doses 76 mg Every 4 Week Dosing Schedule *In patients who have maintained the response following 24 weeks of treatment at the biweekly dosing schedule Week 49 and every 4 weeks thereafter Subsequent treatment doses 76 mg 2.3 Recommended Pre-treatment Medications Administer the following pre-treatment medications approximately 1 hour before the first three doses of ELREXFIO in the step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose as described in Table 1 to reduce the risk of CRS [see Warnings and Precautions (5.1) ] : • acetaminophen (or equivalent) 650 mg orally • dexamethasone (or equivalent) 20 mg orally or intravenously • diphenhydramine (or equivalent) 25 mg orally 2.4 Restarting ELREXFIO After Dosage Delay If a dose of ELREXFIO is delayed, restart therapy based on the recommendations listed in Table 2 and resume the dosing schedule accordingly [see Dosage and Administration (2.2) ] . Administer pre-treatment medications as indicated in Table 2. Table 2. Recommendation for Restarting Therapy with ELREXFIO After Dosage Delay Last Dose Administered Time Since the Last Dose Administered Action for Next Dose Step-up dose 1 (12 mg) 2 weeks or less (≤14 days) Restart ELREXFIO at step-up dose 2 (32 mg). Administer pre-treatment medications prior to the ELREXFIO dose [see Dosage and Administration (2.3) ] . If tolerated, increase to 76 mg 4 days later. Greater than 2 weeks (>14 days) Restart ELREXFIO step-up dosing schedule at step-up dose 1 (12 mg). Step-up dose 2 (32 mg) 2 weeks or less (≤14 days) Restart ELREXFIO at 76 mg. Greater than 2 weeks to less than or equal to 4 weeks (15 days to ≤28 days) Restart ELREXFIO at step-up dose 2 (32 mg). If tolerated, increase to 76 mg 1 week later. Greater than 4 weeks (>28 days) Restart ELREXFIO step-up dosing schedule at step-up dose 1 (12 mg). Any weekly treatment dose (76 mg) 8 weeks or less (≤ 56 days) Restart ELREXFIO at 76 mg. Greater than 8 weeks to less or equal to 12 weeks (57 days to ≤84 days) Consider benefit-risk of restarting ELREXFIO in patients who require a dose delay of more than 56 days due to an adverse reaction. Restart ELREXFIO at step-up dose 2 (32 mg). If tolerated, increase to 76 mg 1 week later. Greater than 12 weeks (>84 days) Restart ELREXFIO step-up dosing schedule at step-up dose 1 (12 mg). Any biweekly or every-4-week treatment dose (76 mg) 12 weeks or less (≤84 days) Restart ELREXFIO at 76 mg . Greater than 12 weeks (>84 days) Restart ELREXFIO step-up dosing schedule at step-up dose 1 (12 mg). 2.5 Dosage Modifications for Adverse Reactions Dosage reductions of ELREXFIO are not recommended. Dosage delays may be required to manage toxicities related to ELREXFIO [see Warnings and Precautions (5) ] . Recommendations on restarting ELREXFIO after a dose delay are provided in Table 2. See Table 3 and Table 4 for recommended actions for adverse reactions of CRS and ICANS, respectively. See Table 5 for recommended actions for neurologic toxicity excluding ICANS and Table 6 for recommended actions for other adverse reactions following administration of ELREXFIO. Consider further management per current practice guidelines. Management of CRS, Neurologic Toxicity Including ICANS Cytokine Release Syndrome (CRS) Management recommendations for CRS are summarized in Table 3. Identify CRS based on clinical presentation [see Warnings and Precautions (5.1) ] . Evaluate and treat other causes of fever, hypoxia, and hypotension. If CRS is suspected, withhold ELREXFIO until CRS resolves. Manage CRS according to the recommendations in Table 3 and consider further management per current practice guidelines. Administer supportive therapy for CRS, which may include intensive care for severe or life-threatening CRS. Consider laboratory testing to monitor for disseminated intravascular coagulation (DIC), hematology parameters, as well as pulmonary, cardiac, renal, and hepatic function. Table 3. Recommendations for Management of CRS Grade Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading criteria for CRS. Presenting Symptoms Actions Grade 1 Temperature ≥100.4 °F (38 °C) Attributed to CRS. Fever may not always be present concurrently with hypotension or hypoxia as it may be masked by interventions such as antipyretics or anti-cytokine therapy. • Withhold ELREXFIO until CRS resolves. See Table 2 for recommendations on restarting ELREXFIO after dose delays. • Administer pretreatment medications prior to next dose of ELREXFIO. Grade 2 Temperature ≥100.4 °F (38 °C) with either: • Hypotension responsive to fluid and not requiring vasopressors, and/or • Oxygen requirement of low-flow nasal cannula Low-flow nasal cannula is ≤6 L/min, and high-flow nasal cannula is >6 L/min. or blow-by • Withhold ELREXFIO until CRS resolves. • Monitor patients daily for 48 hours following the next dose of ELREXFIO. Instruct patients to remain within proximity of a healthcare facility, and consider hospitalization. • Administer pretreatment medications prior to next dose of ELREXFIO. Grade 3 (First occurrence) Temperature ≥100.4 °F (38 °C) with either: • Hypotension requiring one vasopressor with or without vasopressin, and/or • Oxygen requirement of high-flow nasal cannula , facemask, non-rebreather mask, or Venturi mask • Withhold ELREXFIO until CRS resolves. • Provide supportive therapy, which may include intensive care. • Patients should be hospitalized for 48 hours following the next dose of ELREXFIO. • Administer pretreatment medications prior to next dose of ELREXFIO. Grade 3 (Recurrent) Temperature ≥100.4 °F (38 °C) with either: • Hypotension requiring one vasopressor with or without vasopressin, and/or • Oxygen requirement of high-flow nasal cannula , facemask, non-rebreather mask, or Venturi mask • Permanently discontinue therapy with ELREXFIO. • Provide supportive therapy, which may include intensive care. Grade 4 Temperature ≥100.4 °F (38 °C) with either: • Hypotension requiring multiple vasopressors (excluding vasopressin), and/or • Oxygen requirement of positive pressure (e.g., continuous positive airway pressure [CPAP], bilevel positive airway pressure [BiPAP], intubation, and mechanical ventilation) • Permanently discontinue therapy with ELREXFIO. • Provide supportive therapy, which may include intensive care. Neurologic Toxicity Including ICANS Management recommendations for ICANS and neurologic toxicity are summarized in Table 4 and Table 5. At the first sign of neurologic toxicity, including ICANS, withhold ELREXFIO and consider neurology evaluation. Rule out other causes of neurologic symptoms. Provide supportive therapy, which may include intensive care, for severe or life-threatening neurologic toxicities, including ICANS [see Warnings and Precautions (5.2) ] . Manage ICANS according to the recommendations in Table 4 and consider further management per current practice guidelines. Table 4. Recommendations for Management of ICANS Grade Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading criteria for ICANS. Presenting Symptoms Management is determined by the most severe event, not attributable to any other cause. Actions Grade 1 ICE score 7-9 If patient is arousable and able to perform Immune Effector Cell-Associated Encephalopathy (ICE) Assessment, assess: Orientation (oriented to year, month, city, hospital = 4 points); Naming (name 3 objects, e.g., point to clock, pen, button = 3 points); Following Commands (e.g., “show me 2 fingers” or “close your eyes and stick out your tongue” = 1 point); Writing (ability to write a standard sentence = 1 point); and Attention (count backwards from 100 by ten = 1 point). If patient is unarousable and unable to perform ICE Assessment (Grade 4 ICANS) = 0 points. Or depressed level of consciousness Not attributable to any other cause. : awakens spontaneously. • Withhold ELREXFIO until ICANS resolves. See Table 2 for recommendations on restarting ELREXFIO after dose delays. • Monitor neurologic symptoms and consider consultation with a neurologist and other specialists for further evaluation and management. • Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis. Grade 2 ICE score 3-6 Or depressed level of consciousness : awakens to voice. • Withhold ELREXFIO until ICANS resolves. • Administer dexamethasone All references to dexamethasone administration are dexamethasone or equivalent medications. 10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper. • Monitor neurologic symptoms and consider consultation with a neurologist and other specialists for further evaluation and management. • Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis. • Monitor patients daily for 48 hours following the next dose of ELREXFIO. Instruct patients to remain within proximity of a healthcare facility, and consider hospitalization. Grade 3 (First occurrence) ICE score 0-2 or depressed level of consciousness : awakens only to tactile stimulus, or seizures , either: • any clinical seizure, focal or generalized, that resolves rapidly, or • non-convulsive seizures on electroencephalogram (EEG) that resolve with intervention, or raised intracranial pressure: focal/local edema on neuroimaging • Withhold ELREXFIO until ICANS resolves. • Administer dexamethasone 10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper. • Monitor neurologic symptoms and consider consultation with a neurologist and other specialists for further evaluation and management. • Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis. • Provide supportive therapy, which may include intensive care. • Patients should be hospitalized for 48 hours following the next dose of ELREXFIO. Grade 3 (recurrent) ICE score 0-2 or depressed level of consciousness : awakens only to tactile stimulus, or seizures , either: • any clinical seizure, focal or generalized, that resolves rapidly, or • non-convulsive seizures on electroencephalogram (EEG) that resolve with intervention, or raised intracranial pressure: focal/local edema on neuroimaging • Permanently discontinue ELREXFIO. • Administer dexamethasone 10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper. • Monitor neurologic symptoms and consider consultation with a neurologist and other specialists for further evaluation and management. • Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis. • Provide supportive therapy, which may include intensive care. Grade 4 ICE score 0 Or, depressed level of consciousness either: • patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse, or • stupor or coma, or seizures , either: • life-threatening prolonged seizure (>5 minutes), or • repetitive clinical or electrical seizures without return to baseline in between, or motor findings : • deep focal motor weakness such as hemiparesis or paraparesis, or raised intracranial pressure/cerebral edema , with signs/symptoms such as: • diffuse cerebral edema on neuroimaging, or • decerebrate or decorticate posturing, or • cranial nerve VI palsy, or • papilledema, or • Cushing’s triad • Permanently discontinue ELREXFIO. • Administer dexamethasone 10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper. • Alternatively, consider administration of methylprednisolone 1,000 mg per day intravenously for 3 days. • Monitor neurologic symptoms and consider consultation with a neurologist and other specialists for further evaluation and management. • Consider non-sedating, anti-seizure medications (e.g., levetiracetam) for seizure prophylaxis. • Provide supportive therapy, which may include intensive care. Table 5. Recommendations for Management of Neurologic Toxicity, Excluding ICANS Adverse Reaction Severity Actions Neurologic Toxicity (excluding ICANS) Grade 1 • Withhold ELREXFIO until neurologic toxicity symptoms resolve or stabilize. Grade 2 Grade 3 (First occurrence) • Withhold ELREXFIO until neurologic toxicity symptoms improve to Grade 1 or less. • Provide supportive therapy. Grade 3 (Recurrent) Grade 4 • Permanently discontinue ELREXFIO. • Provide supportive therapy, which may include intensive care. Table 6. Recommended Dosage Modifications for Other Adverse Reactions Adverse Reactions Severity Actions Hematologic Adverse Reactions [see Warnings and Precautions (5.5) ] Absolute neutrophil count less than 0.5 x 10 9 /L • Withhold ELREXFIO until absolute neutrophil count is 0.5 x 10 9 /L or higher. See Table 2 for recommendations on restarting ELREXFIO after dose delays. Febrile neutropenia • Withhold ELREXFIO until absolute neutrophil count is 1 x 10 9 /L or higher and fever resolves. Hemoglobin less than 8 g/dL • Withhold ELREXFIO until hemoglobin is 8 g/dL or higher. Platelet count less than 25,000/mcL Platelet count between 25,000/mcL and 50,000/mcL with bleeding • Withhold ELREXFIO until platelet count is 25,000/mcL or higher and no evidence of bleeding. Infections and Other Non-hematologic Adverse Reactions Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5.0. [see Warnings and Precautions (5.4, 5.6) and Adverse Reactions (6.1) ] Grade 3 • Withhold ELREXFIO until adverse reaction improves to ≤Grade 1 or baseline. Grade 4 • Consider permanent discontinuation of ELREXFIO. • If ELREXFIO is not permanently discontinued, withhold subsequent treatment doses of ELREXFIO (e.g., doses administered after ELREXFIO step-up dosing schedule) until adverse reaction improves to Grade 1 or less. 2.6 Preparation and Administration Instructions ELREXFIO is intended for subcutaneous use by a healthcare provider only. ELREXFIO should be administered by a healthcare provider with adequate medical personnel and appropriate medical equipment to manage severe reactions, including CRS and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1 , 5.2 )] . ELREXFIO 76 mg/1.9 mL (40 mg/mL) vial and 44 mg/1.1 mL (40 mg/mL) vial are supplied as ready-to-use solution that do not need dilution prior to administration. ELREXFIO is a clear to slightly opalescent, and colorless to pale brown liquid solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer if solution is discolored or contains particulate matter. Use aseptic technique to prepare and administer ELREXFIO. Preparation ELREXFIO vials are for one-time use in a single patient and do not contain any preservatives. Prepare ELREXFIO following the instructions below (see Table 7 ) depending on the required dose. Table 7. Injection Volumes Total Dose (mg) Volume of Injection 12 mg 0.3 mL 32 mg 0.8 mL 76 mg 1.9 mL Remove the appropriate strength ELREXFIO vial from refrigerated storage [2 °C to 8 °C (36 °F to 46 °F)]. Once removed from refrigerated storage, equilibrate ELREXFIO to ambient temperature [15 °C to 30 °C (59 °F to 86 °F)]. Do not warm ELREXFIO in any other way. Withdraw the required injection volume of ELREXFIO from the vial into an appropriately sized syringe with stainless steel injection needles (30G or wider) and polypropylene or polycarbonate syringe material. Discard unused portion. Administration Inject the required volume of ELREXFIO into the subcutaneous tissue of the abdomen (preferred injection site). Alternatively, ELREXFIO may be injected into the subcutaneous tissue at other sites (e.g., thigh). Do not inject into tattoos or scars or areas where the skin is red, bruised, tender, hard or not intact. Storage of Prepared Syringe If the prepared dosing syringe is not used immediately, the syringe may be stored refrigerated between 2 °C to 8 °C (36 °F to 46 °F) for a maximum of 72 hours or between 8 °C to 25 °C (46 °F to 77 °F) for a maximum of 24 hours. Once removed from refrigerated storage, the prepared syringe must be used or discarded.

None. None. ( 4 )

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) ] . Most common adverse reactions (incidence ≥20%) are 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%) are decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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. System Organ Class Preferred Term ELREXFIO N = 183 All Grades (%) Grade 3 or 4 (%) Immune system disorders Cytokine release syndrome 58 0.5 Only grade 3 adverse reactions occurred. Hypogammaglobulinemia Includes other related terms. 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 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. 32 19 Sepsis 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. 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 Rash incudes erythema, palmar-plantar erythrodysesthesia syndrome, rash, rash erythematous, rash macular, rash maculo-papular, rash pustular, symmetrical drug-related intertriginous and flexural exanthema. 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 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. 14 2.2 Sensory neuropathy Sensory neuropathy includes burning sensation, dysesthesia, hypoesthesia, neuropathy peripheral, paresthesia, parosmia, peripheral sensorimotor neuropathy, peripheral sensory neuropathy, polyneuropathy, sensory loss. 13 0.5 Motor dysfunction Motor dysfunction includes ataxia, balance disorder, gait disturbance, motor dysfunction, muscle contracture, muscle spasms, muscular weakness, peripheral motor neuropathy, peroneal nerve palsy, tremor. 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 and cytomegalovirus infection. 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. Laboratory Abnormality ELREXFIO 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. 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

For certain CYP substrates, minimal changes in the concentration may lead to serious adverse reactions. Monitor for toxicity or drug concentrations of such CYP substrates when co-administered with ELREXFIO. ELREXFIO causes release of cytokines [see Clinical Pharmacology (12.2) ] that may suppress activity of cytochrome P450 (CYP) enzymes, resulting in increased exposure of CYP substrates. Increased exposure of CYP substrates is more likely to occur after the first dose of ELREXFIO Day 1 and up to 14 days after the 32 mg dose on Day 4 and during and after CRS [see Warnings and Precautions (5.1) ] .